Pub Date : 2024-11-15eCollection Date: 2024-01-01DOI: 10.2147/IJN.S484473
Gang Jing, Chen Hu, Keyi Fang, Yingying Li, Linlin Wang
Chronic wound infection has become a global health problem, with bacterial biofilms, which are difficult to penetrate using traditional antibiotics, considered the primary cause of recurrent infection and delayed healing in chronic wounds. In recent years, the outstanding performance of nanomaterials in controlling biofilm infections has been widely acknowledged, and these materials are regarded as highly promising for chronic wound infection management. The formation and structure of chronic wound biofilms undergo complex dynamic changes. Therefore, a deep understanding of the underlying causes of repeated wound infections and the specific antibacterial mechanisms of nanomaterials at different stages of biofilm formation is crucial for effective "chronic wound infection management". This review first reveals the relationship between biofilms, wound chronicity, and recurrent infections. Secondly, it focuses on the four stages of chronic wound biofilm formation: (1) adhesion stage, (2) aggregation and promotion stage, (3) maturation stage, and (4) regeneration and dissemination stage. It also comprehensively summarizes the specific antibacterial mechanisms of nanomaterials. This study analyzes essential factors affecting the control of chronic wound biofilms by nanoparticles from various perspectives, such as the material itself, the local wound environment, and the systemic host response. Finally, the limitations and potential future trends in current research are discussed. In summary, nanoparticles represent a promising strategy for combating chronic wound biofilm infections, and this review provides new insights for alternative adjuvant therapies in managing bacterial biofilm infections in chronic wounds.
{"title":"How Nanoparticles Help in Combating Chronic Wound Biofilms Infection?","authors":"Gang Jing, Chen Hu, Keyi Fang, Yingying Li, Linlin Wang","doi":"10.2147/IJN.S484473","DOIUrl":"https://doi.org/10.2147/IJN.S484473","url":null,"abstract":"<p><p>Chronic wound infection has become a global health problem, with bacterial biofilms, which are difficult to penetrate using traditional antibiotics, considered the primary cause of recurrent infection and delayed healing in chronic wounds. In recent years, the outstanding performance of nanomaterials in controlling biofilm infections has been widely acknowledged, and these materials are regarded as highly promising for chronic wound infection management. The formation and structure of chronic wound biofilms undergo complex dynamic changes. Therefore, a deep understanding of the underlying causes of repeated wound infections and the specific antibacterial mechanisms of nanomaterials at different stages of biofilm formation is crucial for effective \"chronic wound infection management\". This review first reveals the relationship between biofilms, wound chronicity, and recurrent infections. Secondly, it focuses on the four stages of chronic wound biofilm formation: (1) adhesion stage, (2) aggregation and promotion stage, (3) maturation stage, and (4) regeneration and dissemination stage. It also comprehensively summarizes the specific antibacterial mechanisms of nanomaterials. This study analyzes essential factors affecting the control of chronic wound biofilms by nanoparticles from various perspectives, such as the material itself, the local wound environment, and the systemic host response. Finally, the limitations and potential future trends in current research are discussed. In summary, nanoparticles represent a promising strategy for combating chronic wound biofilm infections, and this review provides new insights for alternative adjuvant therapies in managing bacterial biofilm infections in chronic wounds.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11883-11921"},"PeriodicalIF":6.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Abraxane (nanoparticle albumin-bound paclitaxel) is a chemotherapeutic employed commonly for the management of various cancers including breast cancer, non-small cell lung cancer, and pancreatic adenocarcinoma. Although it has clinically beneficial properties, Abraxane is accompanied by multiple adverse events (AEs) that require close observation. This study aims to evaluate the AE profile of Abraxane using recently available data from January 2004 through December 2023 in the FDA Adverse Event Reporting System (FAERS).
Patients and methods: The data for Abraxane-related AEs were obtained from the FAERS database. The dataset consisted of patient demographic characteristics as well as information on the types and outcomes of AEs reported. Reporting odds ratios (ROR) as well as proportional reporting ratio (PRR), considering the used definition of anti-cancer agent and AEs, were calculated to investigate any association with Abraxane.
Results: A total of 10,310 reports associated with Abraxane AEs were identified. Blood and lymphatic system disorders were the most frequent (ROR 6.44), followed by hepatobiliary (ROR 3.16), infections (ROR 1.45), and gastrointestinal disorders (ROR 1.42). Serious outcomes included hospitalization in 36.35% and death in 29.76% of cases. The top adverse reactions matched known profiles, including peripheral sensory neuropathy (ROR: 49.48). The analysis also found new adverse reactions, such as scleroderma-like reactions (ROR: 95.4) and vascular pseudoaneurysm ruptures (ROR: 87.71).
Conclusion: Our results re-emphasize the importance of a robust Post Marketing Surveillance system and suggest this FAERS database based analysis provides an updated, independent information on Abraxane related AEs to enrich its safety profile. A process of continuous vigilance and additional investigations on specific areas that may have some undesired events are imperative to increase our knowledge on how Abraxane should be handled in terms of its safety.
{"title":"Unveiling the Hidden Risks: An Update Decade-Long Analysis of Abraxane-Related Adverse Events from the FAERS Database.","authors":"Yue-Chen Zhao, Xin Li, Chao-Qun Wang, Yan Jiao, Yan-Nan Shen, Tie-Jun Wang, Chao-He Zhang","doi":"10.2147/IJN.S490400","DOIUrl":"10.2147/IJN.S490400","url":null,"abstract":"<p><strong>Purpose: </strong>Abraxane (nanoparticle albumin-bound paclitaxel) is a chemotherapeutic employed commonly for the management of various cancers including breast cancer, non-small cell lung cancer, and pancreatic adenocarcinoma. Although it has clinically beneficial properties, Abraxane is accompanied by multiple adverse events (AEs) that require close observation. This study aims to evaluate the AE profile of Abraxane using recently available data from January 2004 through December 2023 in the FDA Adverse Event Reporting System (FAERS).</p><p><strong>Patients and methods: </strong>The data for Abraxane-related AEs were obtained from the FAERS database. The dataset consisted of patient demographic characteristics as well as information on the types and outcomes of AEs reported. Reporting odds ratios (ROR) as well as proportional reporting ratio (PRR), considering the used definition of anti-cancer agent and AEs, were calculated to investigate any association with Abraxane.</p><p><strong>Results: </strong>A total of 10,310 reports associated with Abraxane AEs were identified. Blood and lymphatic system disorders were the most frequent (ROR 6.44), followed by hepatobiliary (ROR 3.16), infections (ROR 1.45), and gastrointestinal disorders (ROR 1.42). Serious outcomes included hospitalization in 36.35% and death in 29.76% of cases. The top adverse reactions matched known profiles, including peripheral sensory neuropathy (ROR: 49.48). The analysis also found new adverse reactions, such as scleroderma-like reactions (ROR: 95.4) and vascular pseudoaneurysm ruptures (ROR: 87.71).</p><p><strong>Conclusion: </strong>Our results re-emphasize the importance of a robust Post Marketing Surveillance system and suggest this FAERS database based analysis provides an updated, independent information on Abraxane related AEs to enrich its safety profile. A process of continuous vigilance and additional investigations on specific areas that may have some undesired events are imperative to increase our knowledge on how Abraxane should be handled in terms of its safety.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11847-11858"},"PeriodicalIF":6.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-14eCollection Date: 2024-01-01DOI: 10.2147/IJN.S480938
Subhasmita Swain, R D K Misra, Tapash R Rautray
Electroactive components can promote tissue healing and control neuronal activity with the support of the tissue environment and offer electrical impulses and biocompatible material habitats. Due to the increasing growth of portable electronics, it is imperative to generate tiny, lightweight power supply appliances with outstanding performance and sustainable energy conversion ability. In order to deal with the energy deficiency of electronic devices, self-powered systems based nanogenerators are committed to capturing ambient energy for electronic device consumption. Nanogenerator assemblies provide a range of benefits, including adjustable shape, flexibility, affordability, and transportability. As such, they represent a novel and intriguing area for biomedical investigation. In living organisms, bioelectrical mechanisms play an integral part in regulating the functions of cells and tissues. An essential component of electroactive assemblies includes self-powered nanogenerators. In conjunction with nanogenerators, biomedicine has contributed to the invention of medical devices based on self-powered system. Currently, one of the most significant energy-based technologies to guarantee the long-term functioning of implanted biomedical devices is the accumulation of biomechanical energy in vivo. This review covers the development of nanogenerators for biomedical applications. Piezoelectric and triboelectric materials, which could foster the evolution of potential applications in the field of bone regeneration and tissue engineering, are the primary focus of this review. These materials are electrically self-sustaining generators that encourage tissue repair involving osteogenic proliferation, differentiation, and microbial sterilization. Eventually, the discussion highlights the potential future scope and challenges related to the nanogenerators.
{"title":"Nanoscale Generators for Tissue Healing: A Perspective.","authors":"Subhasmita Swain, R D K Misra, Tapash R Rautray","doi":"10.2147/IJN.S480938","DOIUrl":"https://doi.org/10.2147/IJN.S480938","url":null,"abstract":"<p><p>Electroactive components can promote tissue healing and control neuronal activity with the support of the tissue environment and offer electrical impulses and biocompatible material habitats. Due to the increasing growth of portable electronics, it is imperative to generate tiny, lightweight power supply appliances with outstanding performance and sustainable energy conversion ability. In order to deal with the energy deficiency of electronic devices, self-powered systems based nanogenerators are committed to capturing ambient energy for electronic device consumption. Nanogenerator assemblies provide a range of benefits, including adjustable shape, flexibility, affordability, and transportability. As such, they represent a novel and intriguing area for biomedical investigation. In living organisms, bioelectrical mechanisms play an integral part in regulating the functions of cells and tissues. An essential component of electroactive assemblies includes self-powered nanogenerators. In conjunction with nanogenerators, biomedicine has contributed to the invention of medical devices based on self-powered system. Currently, one of the most significant energy-based technologies to guarantee the long-term functioning of implanted biomedical devices is the accumulation of biomechanical energy in vivo. This review covers the development of nanogenerators for biomedical applications. Piezoelectric and triboelectric materials, which could foster the evolution of potential applications in the field of bone regeneration and tissue engineering, are the primary focus of this review. These materials are electrically self-sustaining generators that encourage tissue repair involving osteogenic proliferation, differentiation, and microbial sterilization. Eventually, the discussion highlights the potential future scope and challenges related to the nanogenerators.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11859-11882"},"PeriodicalIF":6.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13eCollection Date: 2024-01-01DOI: 10.2147/IJN.S466363
Rao Chen, Liya Ai, Jiying Zhang, Dong Jiang
Introduction: Tendon injuries present a significant challenge for independent repair, and can progress into tendinopathy over time, highlighting the importance of early intervention. Dendritic cell-derived exosomes (DEXs) has been shown to shift the polarization of M1 macrophages, the predominant inflammatory cells in the early stages of tendon injury. This study introduces a therapeutic approach that effectively manages inflammation while promoting regeneration in the treatment of tendinopathy.
Methods: The purification and characterization of DEXs were meticulously conducted. Experiments were carried out using an Achilles tendon rupture mouse model, with weekly DEXs treatment starting on postoperative day (POD) 4. In vitro, the function of DEXs was assessed by coculturing them with tendon stem/progenitor cells (TSPCs) in culture medium containing IL-1β. Tendon healing progress was evaluated using Sirius Red staining, Masson's trichrome staining, biomechanical testing, and immunofluorescence microscopy. The inflammatory microenvironment of injured tendons was evaluated using the Luminex procedure and flow cytometry analysis.
Results: DEXs treatment significantly enhanced tendon cell differentiation, promoted collagen type I synthesis, and inhibited collagen type III synthesis, thereby expediting tendon healing. Furthermore, DEXs treatment improved the inflammatory microenvironment by reducing multiple cytokines (IL-1β, IL-4, IL-6, TNF-α, and IFN-γ) and induced the conversion of M1 macrophages to M2 macrophages by activating the PI3K/AKT pathway.
Conclusion: DEXs demonstrated a potent ability to promote tendon healing while ameliorating the inflammatory microenvironment, suggesting their potential as a therapeutic approach to prevent the development of tendinopathy.
导言:肌腱损伤是独立修复的重大挑战,随着时间的推移会发展成肌腱病,这凸显了早期干预的重要性。树突状细胞衍生的外泌体(DEXs)已被证明能改变M1巨噬细胞的极化,M1巨噬细胞是肌腱损伤早期的主要炎症细胞。本研究介绍了一种在治疗肌腱病时有效控制炎症同时促进再生的治疗方法:方法:对 DEXs 的纯化和表征进行了细致的研究。在体外,通过在含IL-1β的培养基中与肌腱干/祖细胞(TSPCs)共培养来评估DEXs的功能。使用天狼星红染色、马森三色染色、生物力学测试和免疫荧光显微镜评估了肌腱愈合的进展。使用 Luminex 程序和流式细胞术分析评估了受伤肌腱的炎症微环境:结果:DEXs 能明显促进肌腱细胞分化,促进 I 型胶原蛋白合成,抑制 III 型胶原蛋白合成,从而加快肌腱愈合。此外,DEXs 还能通过减少多种细胞因子(IL-1β、IL-4、IL-6、TNF-α 和 IFN-γ)改善炎症微环境,并通过激活 PI3K/AKT 通路诱导 M1 巨噬细胞向 M2 巨噬细胞转化:结论:DEXs具有促进肌腱愈合的强大能力,同时还能改善炎症微环境,因此有望成为预防肌腱病发展的一种治疗方法。
{"title":"Dendritic Cell-Derived Exosomes Promote Tendon Healing and Regulate Macrophage Polarization in Preventing Tendinopathy.","authors":"Rao Chen, Liya Ai, Jiying Zhang, Dong Jiang","doi":"10.2147/IJN.S466363","DOIUrl":"10.2147/IJN.S466363","url":null,"abstract":"<p><strong>Introduction: </strong>Tendon injuries present a significant challenge for independent repair, and can progress into tendinopathy over time, highlighting the importance of early intervention. Dendritic cell-derived exosomes (DEXs) has been shown to shift the polarization of M1 macrophages, the predominant inflammatory cells in the early stages of tendon injury. This study introduces a therapeutic approach that effectively manages inflammation while promoting regeneration in the treatment of tendinopathy.</p><p><strong>Methods: </strong>The purification and characterization of DEXs were meticulously conducted. Experiments were carried out using an Achilles tendon rupture mouse model, with weekly DEXs treatment starting on postoperative day (POD) 4. In vitro, the function of DEXs was assessed by coculturing them with tendon stem/progenitor cells (TSPCs) in culture medium containing IL-1β. Tendon healing progress was evaluated using Sirius Red staining, Masson's trichrome staining, biomechanical testing, and immunofluorescence microscopy. The inflammatory microenvironment of injured tendons was evaluated using the Luminex procedure and flow cytometry analysis.</p><p><strong>Results: </strong>DEXs treatment significantly enhanced tendon cell differentiation, promoted collagen type I synthesis, and inhibited collagen type III synthesis, thereby expediting tendon healing. Furthermore, DEXs treatment improved the inflammatory microenvironment by reducing multiple cytokines (IL-1β, IL-4, IL-6, TNF-α, and IFN-γ) and induced the conversion of M1 macrophages to M2 macrophages by activating the PI3K/AKT pathway.</p><p><strong>Conclusion: </strong>DEXs demonstrated a potent ability to promote tendon healing while ameliorating the inflammatory microenvironment, suggesting their potential as a therapeutic approach to prevent the development of tendinopathy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11701-11718"},"PeriodicalIF":6.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13eCollection Date: 2024-01-01DOI: 10.2147/IJN.S474299
Minna Han, Zhikuan Xia, Yuekun Zou, Ping Hu, Mingwang Zhang, Xin Yang, Ming-Guo Ma, Rongya Yang
Background: Silver nanomaterials have been widely proven to have antifungal effects against Trichosporon asahii. However, the antifungal mechanism of silver nanomaterials with different morphologies still needs to be explored.
Methods: Herein, the antifungal effect of silver nanomaterials against fungus was comparative investigated via silver nanowires and silver nanoparticles with a similar size (30 nm).
Results: The optimal antifungal concentration of silver nanowires is 6.24 μg/mL, meanwhile the antifungal concentration of silver nanoparticles is 100 μg/mL. The silver nanowires are significantly superior to the silver nanoparticles. SEM and TEM results indicated that both silver nanoparticles and silver nanowires showed significant morphological changes in the mycelium of the strain, compared with the control. The lower MFC value of silver nanowires indicates good sterilization effect and suitability for eradication treatment, which is slower than that of silver nanoparticles. Moreover, we also investigated the toxicological effects of silver nanoparticles and silver nanowires.
Conclusion: We comparative studied and transcriptomic analyzed the antifungal mechanism of Ag nanoparticles and nanowires against Trichosporon asahii. The antifungal effects of silver nanowires were better than the silver nanoparticles, especially in the metabolic processes and oxidative phosphorylation. RNA sequencing results indicated that 15 key targets were selected for experimental verification to interpret the potential antifungal mechanism of Ag nanomaterials against fungus. This work proves that silver nanomaterials with different morphologies have potential applications in fungus therapy such as T. asahii.
{"title":"Comparative Study and Transcriptomic Analysis on the Antifungal Mechanism of Ag Nanoparticles and Nanowires Against <i>Trichosporon asahii</i>.","authors":"Minna Han, Zhikuan Xia, Yuekun Zou, Ping Hu, Mingwang Zhang, Xin Yang, Ming-Guo Ma, Rongya Yang","doi":"10.2147/IJN.S474299","DOIUrl":"10.2147/IJN.S474299","url":null,"abstract":"<p><strong>Background: </strong>Silver nanomaterials have been widely proven to have antifungal effects against <i>Trichosporon asahii</i>. However, the antifungal mechanism of silver nanomaterials with different morphologies still needs to be explored.</p><p><strong>Methods: </strong>Herein, the antifungal effect of silver nanomaterials against fungus was comparative investigated via silver nanowires and silver nanoparticles with a similar size (30 nm).</p><p><strong>Results: </strong>The optimal antifungal concentration of silver nanowires is 6.24 μg/mL, meanwhile the antifungal concentration of silver nanoparticles is 100 μg/mL. The silver nanowires are significantly superior to the silver nanoparticles. SEM and TEM results indicated that both silver nanoparticles and silver nanowires showed significant morphological changes in the mycelium of the strain, compared with the control. The lower MFC value of silver nanowires indicates good sterilization effect and suitability for eradication treatment, which is slower than that of silver nanoparticles. Moreover, we also investigated the toxicological effects of silver nanoparticles and silver nanowires.</p><p><strong>Conclusion: </strong>We comparative studied and transcriptomic analyzed the antifungal mechanism of Ag nanoparticles and nanowires against <i>Trichosporon asahii</i>. The antifungal effects of silver nanowires were better than the silver nanoparticles, especially in the metabolic processes and oxidative phosphorylation. RNA sequencing results indicated that 15 key targets were selected for experimental verification to interpret the potential antifungal mechanism of Ag nanomaterials against fungus. This work proves that silver nanomaterials with different morphologies have potential applications in fungus therapy such as <i>T. asahii</i>.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11789-11804"},"PeriodicalIF":6.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13eCollection Date: 2024-01-01DOI: 10.2147/IJN.S484277
Hany S M Ali, Ahmed F Hanafy, Rawan Bafail, Hamad Alrbyawi, Marey Almaghrabi, Yaser M Alahmadi, Samar El Achy
Background: Budesonide (BUD) is a BCS class II medication with poor water solubility and limited oral bioavailability. In this study, innovative solid self-microemulsifying drug delivery systems (BUD-SMEDDS) were developed for effective local management of distal ulcerative colitis (UC).
Methods: Based on solubility and emulsification tests, the components of the self-microemulsifying drug delivery system (SMEDDS) were Capryol™ 90, Tween 80, and Transcutol HP. The impacts of BUD-SMEDDS ingredients (as inputs) on the average globule size (AGS), polydispersity index (PDI), and self-emulsification time (SET) as responses were investigated using the Box-Behnken design methodology. Solid rectal systems were then fabricated using the optimized values of SMEDDS components in Lutrol® bases. The developed systems were evaluated for in vitro characteristics and in vivo efficacy using a rat colitis model.
Results: For all responses, the greatest impact was attributed to the oil content of SMEDDS. An optimized BUD-SMEDDS with AGS of 33 ± 2.9 nm, PDI of 0.29 ± 0.03 and SET of 25 ± 2.5 s) was selected for rectal formulations. The developed formulations demonstrated acceptable physical characteristics and mucoadhesive abilities. Differential scanning calorimetric (DSC) analysis revealed the absence of BUD crystallinity in the SMEDDS formulations. The drug release patterns could be regulated by selecting the grade and composition of the incorporated Lutrols. Clinical and histopathological assessments revealed considerable improvements in animals treated with BUD-SMEDDS formulations.
Conclusion: Overall findings confirmed the superior capability of solid SMEDDS as BUD carriers to manage distal colitis in tested animals.
{"title":"Locally Acting Budesonide-Loaded Solid Self-Microemulsifying Drug Delivery Systems (SMEDDS) for Distal Ulcerative Colitis.","authors":"Hany S M Ali, Ahmed F Hanafy, Rawan Bafail, Hamad Alrbyawi, Marey Almaghrabi, Yaser M Alahmadi, Samar El Achy","doi":"10.2147/IJN.S484277","DOIUrl":"10.2147/IJN.S484277","url":null,"abstract":"<p><strong>Background: </strong>Budesonide (BUD) is a BCS class II medication with poor water solubility and limited oral bioavailability. In this study, innovative solid self-microemulsifying drug delivery systems (BUD-SMEDDS) were developed for effective local management of distal ulcerative colitis (UC).</p><p><strong>Methods: </strong>Based on solubility and emulsification tests, the components of the self-microemulsifying drug delivery system (SMEDDS) were Capryol™ 90, Tween 80, and Transcutol HP. The impacts of BUD-SMEDDS ingredients (as inputs) on the average globule size (AGS), polydispersity index (PDI), and self-emulsification time (SET) as responses were investigated using the Box-Behnken design methodology. Solid rectal systems were then fabricated using the optimized values of SMEDDS components in Lutrol<sup>®</sup> bases. The developed systems were evaluated for in vitro characteristics and in vivo efficacy using a rat colitis model.</p><p><strong>Results: </strong>For all responses, the greatest impact was attributed to the oil content of SMEDDS. An optimized BUD-SMEDDS with AGS of 33 ± 2.9 nm, PDI of 0.29 ± 0.03 and SET of 25 ± 2.5 s) was selected for rectal formulations. The developed formulations demonstrated acceptable physical characteristics and mucoadhesive abilities. Differential scanning calorimetric (DSC) analysis revealed the absence of BUD crystallinity in the SMEDDS formulations. The drug release patterns could be regulated by selecting the grade and composition of the incorporated Lutrols. Clinical and histopathological assessments revealed considerable improvements in animals treated with BUD-SMEDDS formulations.</p><p><strong>Conclusion: </strong>Overall findings confirmed the superior capability of solid SMEDDS as BUD carriers to manage distal colitis in tested animals.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11819-11846"},"PeriodicalIF":6.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13eCollection Date: 2024-01-01DOI: 10.2147/IJN.S484976
Meilin Zhu, Lingzhou Zhao, Xia Lu
Purpose: Gold nanoparticles (Au NPs) are widely used as versatile templates to develop multifunctional nanosystems for disease diagnosis and treatment. Iodine can bind to gold via chemisorption, making this a simple method for labeling Au NPs with radioactive iodine. However, the evaluation of tumor radionuclide therapy is insufficient. In this study, we investigated the feasibility of 131I-adsorbed Au NPs as novel nanoprobes for tumor radionuclide therapy.
Materials and methods: Radiolabeling was performed by mixing Au NPs and 131I, and the radiochemical purity (RCP) and in vitro stability of 131I-adsorbed Au NPs were analyzed under different conditions, including various temperatures, pH values, and 131I concentrations. The tumor accumulation and therapeutic potential of 131I-adsorbed Au NPs were assessed using a subcutaneous tumor model after intratumoral injection.
Results: The data showed that the chemisorption of the Au NPs onto 131I was instant, specific, and quantitative. The 131I-adsorbed Au NPs exhibited high in vitro stability in different media, distinct inhibitory effects on tumor cells in vitro, good retention ability, and therapeutic effects after intratumoral injection into tumor-bearing mice in vivo.
Conclusion: Our work demonstrates that chemisorption of Au NPs and radioiodine has great potential as a strategy for constructing various nanosystems for theranostic applications.
目的:金纳米粒子(Au NPs)被广泛用作多功能模板,用于开发疾病诊断和治疗的多功能纳米系统。碘可以通过化学吸附作用与金结合,这使得用放射性碘标记金纳米粒子成为一种简单的方法。然而,对肿瘤放射性核素治疗的评估还不够充分。在这项研究中,我们探讨了吸附 131I 的 Au NPs 作为新型纳米探针用于肿瘤放射性核素治疗的可行性:将 Au NPs 与 131I 混合进行放射性标记,在不同温度、pH 值和 131I 浓度等条件下分析吸附 131I 的 Au NPs 的放射化学纯度(RCP)和体外稳定性。采用皮下注射肿瘤模型评估了吸附 131I 的 Au NPs 的肿瘤蓄积和治疗潜力:数据显示,金氧化物对 131I 的化学吸附是即时、特异和定量的。吸附了 131I 的 Au NPs 在不同介质中表现出较高的体外稳定性,在体外对肿瘤细胞有明显的抑制作用,具有良好的保留能力,在体内向肿瘤小鼠进行瘤内注射后具有治疗效果:我们的研究表明,金氧化物和放射性碘的化学吸附作为一种构建各种治疗应用纳米系统的策略,具有巨大的潜力。
{"title":"Direct Labeling of Gold Nanoparticles with Iodine-131 for Tumor Radionuclide Therapy.","authors":"Meilin Zhu, Lingzhou Zhao, Xia Lu","doi":"10.2147/IJN.S484976","DOIUrl":"10.2147/IJN.S484976","url":null,"abstract":"<p><strong>Purpose: </strong>Gold nanoparticles (Au NPs) are widely used as versatile templates to develop multifunctional nanosystems for disease diagnosis and treatment. Iodine can bind to gold via chemisorption, making this a simple method for labeling Au NPs with radioactive iodine. However, the evaluation of tumor radionuclide therapy is insufficient. In this study, we investigated the feasibility of <sup>131</sup>I-adsorbed Au NPs as novel nanoprobes for tumor radionuclide therapy.</p><p><strong>Materials and methods: </strong>Radiolabeling was performed by mixing Au NPs and <sup>131</sup>I, and the radiochemical purity (RCP) and in vitro stability of <sup>131</sup>I-adsorbed Au NPs were analyzed under different conditions, including various temperatures, pH values, and <sup>131</sup>I concentrations. The tumor accumulation and therapeutic potential of <sup>131</sup>I-adsorbed Au NPs were assessed using a subcutaneous tumor model after intratumoral injection.</p><p><strong>Results: </strong>The data showed that the chemisorption of the Au NPs onto <sup>131</sup>I was instant, specific, and quantitative. The <sup>131</sup>I-adsorbed Au NPs exhibited high in vitro stability in different media, distinct inhibitory effects on tumor cells in vitro, good retention ability, and therapeutic effects after intratumoral injection into tumor-bearing mice in vivo.</p><p><strong>Conclusion: </strong>Our work demonstrates that chemisorption of Au NPs and radioiodine has great potential as a strategy for constructing various nanosystems for theranostic applications.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11805-11818"},"PeriodicalIF":6.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Erectile dysfunction (ED) frequently arises as a complication of pelvic surgeries, including rectal and prostate surgery, and has no definitive cure. This study explored whether mitochondria-rich microvesicles (MVs) can be used to treat ED stemming from cavernous nerve injury (CNI) and investigated its potential mechanisms.
Methods: We isolated MVs and mitochondria (MT) from PC12. The apoptosis rate, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial derived reactive oxygen species (mtROS), iron content, malondialdehyde (MDA) content and endogenous antioxidant system activity of corpus cavernosum smooth muscle cells (CCSMCs) cultured with MVs and MT were detected in vitro. In vivo, twenty-four male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI group were injected with PBS, MVs and MT respectively. After fourteen days of treatment, the erectile function was measured and penile tissues were collected for histological analysis. Subsequently, inhibition of mitochondria in MV was performed to explore the mechanism of the rescue experiment.
Results: The CCSMCs, PC12-MVs and PC12-MT were successfully isolated and identified. After MVs culture, apoptosis rate, ROS, mtROS, iron content and MDA content of CCSMCs were significantly decreased, while MMP and the activities of endogenous antioxidant system were increased. MVs transplantation can significantly restore erectile function and smooth muscle content in CNIED rats. The rescue experiment suggested that MVs exerted the above therapeutic effect by transferring mitochondria within it.
Conclusion: MVs transplantation significantly improve erectile function in CNI ED rats. MVs may play a role in anti-OS and anti-ferroptosis at the transplant site through efficient transfer of mitochondria, providing a potential treatment vehicle for CNI ED.
目的:勃起功能障碍(ED)是直肠和前列腺等盆腔手术的常见并发症,目前尚无根治方法。本研究探讨了富含线粒体的微囊(MVs)是否可用于治疗海绵体神经损伤(CNI)引起的勃起功能障碍,并研究了其潜在机制:方法:我们从PC12中分离出微囊泡和线粒体(MT)。方法:我们从 PC12 中分离出中胚层细胞和线粒体,并在体外检测了用中胚层细胞和线粒体培养的海绵体平滑肌细胞(CCSMC)的凋亡率、线粒体膜电位(MMP)、活性氧(ROS)、线粒体衍生活性氧(mtROS)、铁含量、丙二醛(MDA)含量和内源性抗氧化系统活性。在体内,将 24 只雄性 Sprague Dawley 大鼠随机分为四组:假手术组和 CNI 组,分别注射 PBS、MVs 和 MT。治疗十四天后,测量阴茎勃起功能并收集阴茎组织进行组织学分析。随后,进行了抑制 MV 中线粒体的实验,以探讨挽救实验的机制:结果:成功分离并鉴定了CCSMCs、PC12-MVs和PC12-MT。MVs培养后,CCSMCs的凋亡率、ROS、mtROS、铁含量和MDA含量明显降低,而MMP和内源性抗氧化系统的活性增加。中浆细胞移植能明显恢复 CNIED 大鼠的勃起功能和平滑肌含量。拯救实验表明,MVs 是通过转移其中的线粒体而发挥上述治疗作用的:结论:线粒体移植能明显改善 CNI ED 大鼠的勃起功能。结论:MVs 移植可明显改善 CNI ED 大鼠的勃起功能,MVs 可通过线粒体的有效转移在移植部位发挥抗 OS 和抗肥大的作用,为 CNI ED 提供了一种潜在的治疗载体。
{"title":"Mitochondria-Rich Microvesicles Alleviate CNI ED by Transferring Mitochondria and Suppressing Local Ferroptosis.","authors":"Zhenkang Liang, Zehong Chen, Chaowei Zhang, Cui Chen, Wende Yang, Yuxuan Zhang, Hongbo Wei","doi":"10.2147/IJN.S488163","DOIUrl":"10.2147/IJN.S488163","url":null,"abstract":"<p><strong>Purpose: </strong>Erectile dysfunction (ED) frequently arises as a complication of pelvic surgeries, including rectal and prostate surgery, and has no definitive cure. This study explored whether mitochondria-rich microvesicles (MVs) can be used to treat ED stemming from cavernous nerve injury (CNI) and investigated its potential mechanisms.</p><p><strong>Methods: </strong>We isolated MVs and mitochondria (MT) from PC12. The apoptosis rate, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial derived reactive oxygen species (mtROS), iron content, malondialdehyde (MDA) content and endogenous antioxidant system activity of corpus cavernosum smooth muscle cells (CCSMCs) cultured with MVs and MT were detected in vitro. In vivo, twenty-four male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI group were injected with PBS, MVs and MT respectively. After fourteen days of treatment, the erectile function was measured and penile tissues were collected for histological analysis. Subsequently, inhibition of mitochondria in MV was performed to explore the mechanism of the rescue experiment.</p><p><strong>Results: </strong>The CCSMCs, PC12-MVs and PC12-MT were successfully isolated and identified. After MVs culture, apoptosis rate, ROS, mtROS, iron content and MDA content of CCSMCs were significantly decreased, while MMP and the activities of endogenous antioxidant system were increased. MVs transplantation can significantly restore erectile function and smooth muscle content in CNIED rats. The rescue experiment suggested that MVs exerted the above therapeutic effect by transferring mitochondria within it.</p><p><strong>Conclusion: </strong>MVs transplantation significantly improve erectile function in CNI ED rats. MVs may play a role in anti-OS and anti-ferroptosis at the transplant site through efficient transfer of mitochondria, providing a potential treatment vehicle for CNI ED.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11745-11765"},"PeriodicalIF":6.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-11eCollection Date: 2024-01-01DOI: 10.2147/IJN.S496028
Yong-Gyu Jeong, Joo-Hwan Park, Dongwoo Khang
The advent of acoustically responsive nanodrugs that are specifically optimized for sonodynamic therapy (SDT) is a novel approach for clinical applications. Examining the therapeutic applications of sono-responsive drug delivery systems, understanding their dynamic response to acoustic stimuli, and their crucial role in enhancing targeted drug delivery are intriguing issues for current cancer treatment. Specifically, the suggested review covers SDT, a modality that enhances the cytotoxic activity of specific compounds (sonosensitizers) using ultrasound (US). Notably, SDT offers significant advantages in cancer treatment by utilizing US energy to precisely target and activate sonosensitizers toward deep-seated malignant sites. The potential mechanisms underlying SDT involve the generation of radicals from sonosensitizers, physical disruption of cell membranes, and enhanced drug transport into cells via US-assisted sonoporation. In particular, SDT is emerging as a promising modality for noninvasive, site-directed elimination of solid tumors. Given the complexity and diversity of tumors, many studies have explored the integration of SDT with other treatments to enhance the overall efficacy. This trend has paved the way for SDT-based multimodal synergistic cancer therapies, including sonophototherapy, sonoimmunotherapy, and sonochemotherapy. Representative studies of these multimodal approaches are comprehensively presented, with a detailed discussion of their underlying mechanisms. Additionally, the application of audible sound waves in biological systems is explored, highlighting their potential to influence cellular processes and enhance therapeutic outcomes. Audible sound waves can modulate enzyme activities and affect cell behavior, providing novel avenues for the use of sound-based techniques in medical applications. This review highlights the current challenges and prospects in the development of SDT-based nanomedicines in this rapidly evolving research field. The anticipated growth of this SDT-based therapeutic approach promises to significantly improve the precision of cancer treatment.
专为声动力疗法(SDT)优化的声响应纳米药物的出现是临床应用的一种新方法。研究声响应给药系统的治疗应用,了解其对声学刺激的动态响应,以及它们在增强靶向给药方面的关键作用,是当前癌症治疗中引人关注的问题。具体而言,建议的综述涉及 SDT,这是一种利用超声波(US)增强特定化合物(声敏化剂)细胞毒性活性的模式。值得注意的是,SDT 在癌症治疗中具有显著优势,它利用 US 能量将声波增敏剂精确瞄准并激活深层恶性部位。SDT 的潜在机制包括声波增敏剂产生自由基、对细胞膜造成物理破坏以及通过 US 辅助的声波修复增强药物在细胞内的传输。特别是,SDT 正在成为一种很有前景的非侵入性、定点消除实体肿瘤的方法。鉴于肿瘤的复杂性和多样性,许多研究都在探索将 SDT 与其他治疗方法相结合,以提高整体疗效。这一趋势为基于 SDT 的多模式协同癌症疗法铺平了道路,包括声光疗法、声免疫疗法和声化学疗法。本文全面介绍了这些多模式疗法的代表性研究,并对其基本机制进行了详细讨论。此外,还探讨了声波在生物系统中的应用,强调了声波影响细胞过程和提高治疗效果的潜力。可听声波可以调节酶的活性并影响细胞的行为,为在医学应用中使用声基技术提供了新的途径。本综述重点介绍了在这一快速发展的研究领域开发基于 SDT 的纳米药物所面临的挑战和前景。这种基于 SDT 的治疗方法的预期发展有望显著提高癌症治疗的精确性。
{"title":"Sonodynamic and Acoustically Responsive Nanodrug Delivery System: Cancer Application.","authors":"Yong-Gyu Jeong, Joo-Hwan Park, Dongwoo Khang","doi":"10.2147/IJN.S496028","DOIUrl":"10.2147/IJN.S496028","url":null,"abstract":"<p><p>The advent of acoustically responsive nanodrugs that are specifically optimized for sonodynamic therapy (SDT) is a novel approach for clinical applications. Examining the therapeutic applications of sono-responsive drug delivery systems, understanding their dynamic response to acoustic stimuli, and their crucial role in enhancing targeted drug delivery are intriguing issues for current cancer treatment. Specifically, the suggested review covers SDT, a modality that enhances the cytotoxic activity of specific compounds (sonosensitizers) using ultrasound (US). Notably, SDT offers significant advantages in cancer treatment by utilizing US energy to precisely target and activate sonosensitizers toward deep-seated malignant sites. The potential mechanisms underlying SDT involve the generation of radicals from sonosensitizers, physical disruption of cell membranes, and enhanced drug transport into cells via US-assisted sonoporation. In particular, SDT is emerging as a promising modality for noninvasive, site-directed elimination of solid tumors. Given the complexity and diversity of tumors, many studies have explored the integration of SDT with other treatments to enhance the overall efficacy. This trend has paved the way for SDT-based multimodal synergistic cancer therapies, including sonophototherapy, sonoimmunotherapy, and sonochemotherapy. Representative studies of these multimodal approaches are comprehensively presented, with a detailed discussion of their underlying mechanisms. Additionally, the application of audible sound waves in biological systems is explored, highlighting their potential to influence cellular processes and enhance therapeutic outcomes. Audible sound waves can modulate enzyme activities and affect cell behavior, providing novel avenues for the use of sound-based techniques in medical applications. This review highlights the current challenges and prospects in the development of SDT-based nanomedicines in this rapidly evolving research field. The anticipated growth of this SDT-based therapeutic approach promises to significantly improve the precision of cancer treatment.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11767-11788"},"PeriodicalIF":6.6,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-11eCollection Date: 2024-01-01DOI: 10.2147/IJN.S485106
Petro Virych, Pavlo Virych, Volodymyr Prokopiuk, Anatolii Onishchenko, Mykola Ischenko, Volodymyr Doroschuk, Valentyna Kurovska, Anton Tkachenko, Nataliya Kutsevol
Introduction: Tumor drug resistance and systemic toxicity are major challenges of modern anticancer therapy. Nanotechnology makes it possible to create new materials with the required properties for anticancer therapy.
Methods: In this research, Dextran-graft-Polyacrylamide/ZnO nanoparticles were used. The study was carried out using prostate (DU-145, LNCaP, PC-3), breast (MDA-MB-231, MCF-7, MCF-7 Dox) cancer cells and non-malignant (MAEC, BALB/3T3 clone A31) cells. Zinc was visualized with fluorescence in vitro and in vivo. ROS and apoptotic markers were identified by cytometry. Zinc accumulation and histopathological changes in the tumor, liver, kidney, and spleen were evaluated in a rat model.
Results: ZnO nanoparticles dissociation and release of Zn2+ into the cytosol occurs in 2-3 hours for cancerous and non-cancerous cells. ROS upregulation was detected in all cells. For non-malignant cells, the difference between the initial ROS level was insignificant. The rate of carbohydrate metabolism in cancer cells was reduced by nanosystems. Zinc level in the tumor was upregulated by 25% and 39% after treatment with nanosystems and doxorubicin combined, respectively. The tumor Walker-256 carcinosarcoma volume was reduced twice following mono-treatment with the nanocomplex and 65-fold lower when the nanocomplex was combined with doxorubicin compared with controls. In the liver, kidney and spleen, the zinc level increased by 10-15% but no significant pathological alterations in the tissues were detected.
Conclusion: D-PAA/ZnO NPs nanosystems were internalized by prostate, breast cancer cells and non-malignant cells via endocytosis after short time, but cytotoxicity against non-cancer cells were significantly lower in vitro and in vivo. D-PAA/ZnO NPs nanocomplex efficiently promoted cell death of tumor cells without showing cytotoxicity against non-malignant cells making it a promising anti-cancer agent.
{"title":"Dextran-Graft-Polyacrylamide/Zinc Oxide Nanoparticles Inhibit of Cancer Cells in vitro and in vivo.","authors":"Petro Virych, Pavlo Virych, Volodymyr Prokopiuk, Anatolii Onishchenko, Mykola Ischenko, Volodymyr Doroschuk, Valentyna Kurovska, Anton Tkachenko, Nataliya Kutsevol","doi":"10.2147/IJN.S485106","DOIUrl":"10.2147/IJN.S485106","url":null,"abstract":"<p><strong>Introduction: </strong>Tumor drug resistance and systemic toxicity are major challenges of modern anticancer therapy. Nanotechnology makes it possible to create new materials with the required properties for anticancer therapy.</p><p><strong>Methods: </strong>In this research, Dextran-graft-Polyacrylamide/ZnO nanoparticles were used. The study was carried out using prostate (DU-145, LNCaP, PC-3), breast (MDA-MB-231, MCF-7, MCF-7 Dox) cancer cells and non-malignant (MAEC, BALB/3T3 clone A31) cells. Zinc was visualized with fluorescence in vitro and in vivo. ROS and apoptotic markers were identified by cytometry. Zinc accumulation and histopathological changes in the tumor, liver, kidney, and spleen were evaluated in a rat model.</p><p><strong>Results: </strong>ZnO nanoparticles dissociation and release of Zn<sup>2+</sup> into the cytosol occurs in 2-3 hours for cancerous and non-cancerous cells. ROS upregulation was detected in all cells. For non-malignant cells, the difference between the initial ROS level was insignificant. The rate of carbohydrate metabolism in cancer cells was reduced by nanosystems. Zinc level in the tumor was upregulated by 25% and 39% after treatment with nanosystems and doxorubicin combined, respectively. The tumor Walker-256 carcinosarcoma volume was reduced twice following mono-treatment with the nanocomplex and 65-fold lower when the nanocomplex was combined with doxorubicin compared with controls. In the liver, kidney and spleen, the zinc level increased by 10-15% but no significant pathological alterations in the tissues were detected.</p><p><strong>Conclusion: </strong>D-PAA/ZnO NPs nanosystems were internalized by prostate, breast cancer cells and non-malignant cells via endocytosis after short time, but cytotoxicity against non-cancer cells were significantly lower in vitro and in vivo. D-PAA/ZnO NPs nanocomplex efficiently promoted cell death of tumor cells without showing cytotoxicity against non-malignant cells making it a promising anti-cancer agent.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11719-11743"},"PeriodicalIF":6.6,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}