Aims: The objective of the present study was to develop and characterize tamoxifen (TAM)-loaded TPGS-PLGA nanoparticles (NPs) for more effective breast cancer treatment than conventional therapy.
Materials and methods: TAM@TPGS-PLGA-NPs were developed using the emulsion-solvent evaporation method. Furthermore, various physicochemical characterizations were performed. In addition, cytotoxicity, in vitro hemocompatibility, histopathological, and imaging studies were conducted to evaluate the safety and efficacy of the formulation.
Results: TAM@TPGS-PLGA-NPs had a particle size of 171.5 ± 7.3 nm, zeta potential of +34.08 ± 3.14 mV, and an entrapment efficiency was found to be 93.64 ± 1.86%, respectively. At an acidic pH of 5.5, TAM@TPGS-PLGA-NPs exhibited higher drug release compared to pH 7.4. In vitro cytotoxicity study revealed that TAM@TPGS-PLGA-NPs were 6.21-fold more cytotoxic than free TAM. The formulation exhibited excellent hemocompatibility and organ safety. In vivo ultrasound/photoacoustic imaging confirmed tumor-selective accumulation and significantly suppressed tumor progression in the DMBA-induced female SD rats breast cancer model.
Discussion: The developed TAM@TPGS-PLGA-NPs demonstrated enhanced drug release in the tumor microenvironment, significantly improved cytotoxicity, and excellent biocompatibility compared to the free drug. These findings indicate their strong potential for tumor-targeted breast cancer therapy with reduced systemic toxicity and enhanced therapeutic efficacy.
{"title":"Tamoxifen-loaded TPGS-PLGA nanoplatform for breast cancer therapy: insights into drug delivery, distribution, treatment efficacy, and ultrasound/photoacoustic imaging.","authors":"Dipali Patil, Vaishali, Nandini Vinodrao Randhave, Aseem Setia, Vikas Kumar, Komal Rani, Nidhi Verma, Nishi Agrawal, Madaswamy S Muthu","doi":"10.1080/17435889.2026.2624743","DOIUrl":"https://doi.org/10.1080/17435889.2026.2624743","url":null,"abstract":"<p><strong>Aims: </strong>The objective of the present study was to develop and characterize tamoxifen (TAM)-loaded TPGS-PLGA nanoparticles (NPs) for more effective breast cancer treatment than conventional therapy.</p><p><strong>Materials and methods: </strong>TAM@TPGS-PLGA-NPs were developed using the emulsion-solvent evaporation method. Furthermore, various physicochemical characterizations were performed. In addition, cytotoxicity, <i>in vitro</i> hemocompatibility, histopathological, and imaging studies were conducted to evaluate the safety and efficacy of the formulation.</p><p><strong>Results: </strong>TAM@TPGS-PLGA-NPs had a particle size of 171.5 ± 7.3 nm, zeta potential of +34.08 ± 3.14 mV, and an entrapment efficiency was found to be 93.64 ± 1.86%, respectively. At an acidic pH of 5.5, TAM@TPGS-PLGA-NPs exhibited higher drug release compared to pH 7.4. <i>In vitro</i> cytotoxicity study revealed that TAM@TPGS-PLGA-NPs were 6.21-fold more cytotoxic than free TAM. The formulation exhibited excellent hemocompatibility and organ safety. <i>In vivo</i> ultrasound/photoacoustic imaging confirmed tumor-selective accumulation and significantly suppressed tumor progression in the DMBA-induced female SD rats breast cancer model.</p><p><strong>Discussion: </strong>The developed TAM@TPGS-PLGA-NPs demonstrated enhanced drug release in the tumor microenvironment, significantly improved cytotoxicity, and excellent biocompatibility compared to the free drug. These findings indicate their strong potential for tumor-targeted breast cancer therapy with reduced systemic toxicity and enhanced therapeutic efficacy.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"1-12"},"PeriodicalIF":3.9,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.1080/17435889.2026.2628309
Hongqin Yu, Shuai Li, Hongtao Niu, Zhao Li, Yusheng Gai, Bei Sun, Lan Zhao
Objective: To develop a novel lipid nanoparticle (Ato@DSPE-PEG-CHP) for targeted delivery to ischemic myocardium to treat myocardial infarction.
Methods: Ato@DSPE-PEG-CHP was prepared using the thin-film dispersion method. Physicochemical properties were characterized by transmission electron microscope (TEM) and dynamic light scattering (DLS). In vitro targeting, uptake, and cytotoxicity were evaluated in OGD/R-treated HL-1 cells using confocal microscopy and CCK8. In vivo, a mouse MI model was established by ligating the left anterior descending coronary artery. The targeted distribution was observed using small animal in vivo imaging. Efficacy was evaluated using TTC, HE, Masson and TUNEL staining. Biosafety was evaluated through hemolysis assays and histopathological analysis.
Results: Ato@DSPE-PEG-CHP with uniform morphology, excellent dispersibility, and high stability were successfully prepared. This material can target myocardial ischemia sites both in vitro and in vivo. Ato@DSPE-PEG-CHP reduced infarct size, cell necrosis, inflammation, fibrosis, and apoptosis; decreased levels of tumor necrosis factor-α, interleukin-6, and malondialdehyde; and increased the enzyme activity of superoxide dismutase. Additionally, it demonstrated good biocompatibility and exhibited no significant toxicity to major organs.
Conclusion: Ato@DSPE-PEG-CHP specifically targeted ischemic myocardium, alleviated damage through its anti-inflammatory and antioxidant effects, and demonstrated superior efficacy and safety, presenting a promising treatment strategy for MI.
{"title":"Precise atorvastatin delivery by cardiac homing peptide functionalized nanoliposomes for myocardial damage repair after myocardial infarction.","authors":"Hongqin Yu, Shuai Li, Hongtao Niu, Zhao Li, Yusheng Gai, Bei Sun, Lan Zhao","doi":"10.1080/17435889.2026.2628309","DOIUrl":"https://doi.org/10.1080/17435889.2026.2628309","url":null,"abstract":"<p><strong>Objective: </strong>To develop a novel lipid nanoparticle (Ato@DSPE-PEG-CHP) for targeted delivery to ischemic myocardium to treat myocardial infarction.</p><p><strong>Methods: </strong>Ato@DSPE-PEG-CHP was prepared using the thin-film dispersion method. Physicochemical properties were characterized by transmission electron microscope (TEM) and dynamic light scattering (DLS). <i>In vitro</i> targeting, uptake, and cytotoxicity were evaluated in OGD/R-treated HL-1 cells using confocal microscopy and CCK8. In vivo, a mouse MI model was established by ligating the left anterior descending coronary artery. The targeted distribution was observed using small animal <i>in vivo</i> imaging. Efficacy was evaluated using TTC, HE, Masson and TUNEL staining. Biosafety was evaluated through hemolysis assays and histopathological analysis.</p><p><strong>Results: </strong>Ato@DSPE-PEG-CHP with uniform morphology, excellent dispersibility, and high stability were successfully prepared. This material can target myocardial ischemia sites both <i>in vitro</i> and <i>in vivo</i>. Ato@DSPE-PEG-CHP reduced infarct size, cell necrosis, inflammation, fibrosis, and apoptosis; decreased levels of tumor necrosis factor-α, interleukin-6, and malondialdehyde; and increased the enzyme activity of superoxide dismutase. Additionally, it demonstrated good biocompatibility and exhibited no significant toxicity to major organs.</p><p><strong>Conclusion: </strong>Ato@DSPE-PEG-CHP specifically targeted ischemic myocardium, alleviated damage through its anti-inflammatory and antioxidant effects, and demonstrated superior efficacy and safety, presenting a promising treatment strategy for MI.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"1-13"},"PeriodicalIF":3.9,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146145059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-04DOI: 10.1080/17435889.2026.2623975
Jiashuo Liu, Luhao Sun, Lei Luo, Yuhang Du, Yang Wang, Kai Feng, Qing Li, Xuetao Xie
Aim: Osteoarthritis (OA) is a prevalent degenerative joint disease characterized primarily by chronic pain. Currently, there are no highly effective treatments for OA pain. This study aimed to assess the efficacy of M2 macrophage-derived small extracellular vesicles (M2-sEVs) in treating OA and alleviating its associated pain, and to investigate their mechanism of action in pain relief.
Methods: M2-sEVs were isolated via ultracentrifugation. A sodium iodoacetate-induced rat OA model was established to assess the effects of M2-sEVs. RNA sequencing was utilized to identify the molecular mechanisms underlying these analgesic effects, with subsequent validation experiments conducted via RT-qPCR, Western blot, and ELISA assays. Human end-stage OA synovial tissues cultured ex vivo were also utilized to confirm clinical relevance.
Results: M2-sEVs administration alleviated pain behaviors and joint pathology in OA rats, suppressing pain-related molecules in synovium and dorsal root ganglia. Mechanistically, M2-sEVs inhibited synovial macrophage-derived nerve growth factor (NGF) by modulating the Notch pathway. Importantly, this therapeutic mechanism was validated in ex vivo cultured human synovial tissues.
Conclusion: M2-sEVs effectively reduce OA-related pain by suppressing macrophage-derived NGF expression via the Notch pathway, highlighting their promising potential as a nanomedicine-based therapeutic strategy for OA pain management.
{"title":"M2-sEVs-based immunotherapy for alleviation of osteoarthritis-related pain by regulating synovial macrophage NGF expression via the NOTCH pathway.","authors":"Jiashuo Liu, Luhao Sun, Lei Luo, Yuhang Du, Yang Wang, Kai Feng, Qing Li, Xuetao Xie","doi":"10.1080/17435889.2026.2623975","DOIUrl":"https://doi.org/10.1080/17435889.2026.2623975","url":null,"abstract":"<p><strong>Aim: </strong>Osteoarthritis (OA) is a prevalent degenerative joint disease characterized primarily by chronic pain. Currently, there are no highly effective treatments for OA pain. This study aimed to assess the efficacy of M2 macrophage-derived small extracellular vesicles (M2-sEVs) in treating OA and alleviating its associated pain, and to investigate their mechanism of action in pain relief.</p><p><strong>Methods: </strong>M2-sEVs were isolated via ultracentrifugation. A sodium iodoacetate-induced rat OA model was established to assess the effects of M2-sEVs. RNA sequencing was utilized to identify the molecular mechanisms underlying these analgesic effects, with subsequent validation experiments conducted via RT-qPCR, Western blot, and ELISA assays. Human end-stage OA synovial tissues cultured ex vivo were also utilized to confirm clinical relevance.</p><p><strong>Results: </strong>M2-sEVs administration alleviated pain behaviors and joint pathology in OA rats, suppressing pain-related molecules in synovium and dorsal root ganglia. Mechanistically, M2-sEVs inhibited synovial macrophage-derived nerve growth factor (NGF) by modulating the Notch pathway. Importantly, this therapeutic mechanism was validated in ex vivo cultured human synovial tissues.</p><p><strong>Conclusion: </strong>M2-sEVs effectively reduce OA-related pain by suppressing macrophage-derived NGF expression via the Notch pathway, highlighting their promising potential as a nanomedicine-based therapeutic strategy for OA pain management.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"1-16"},"PeriodicalIF":3.9,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-03DOI: 10.1080/17435889.2026.2623935
Chloe E Shenouda, Tiana V Sharpe, Jacob W Campbell, Carlie L Charron
In this review, applications of engineered peptide nanomaterials in enhanced cancer imaging are summarized, focusing on the most pertinent of reports. The design principles of said peptide nanostructures are outlined as well as their functionalization for imaging modalities and tumor targeting. The landscape of the field is explored and areas that were deemed underdeveloped are highlighted. Finally, the challenges and limitations that must be overcome to enable the wider clinical adoption of peptide-based nanomaterials in cancer imaging are discussed, and future perspectives are offered.
{"title":"Applications of engineered peptide nanomaterials in enhanced cancer imaging.","authors":"Chloe E Shenouda, Tiana V Sharpe, Jacob W Campbell, Carlie L Charron","doi":"10.1080/17435889.2026.2623935","DOIUrl":"https://doi.org/10.1080/17435889.2026.2623935","url":null,"abstract":"<p><p>In this review, applications of engineered peptide nanomaterials in enhanced cancer imaging are summarized, focusing on the most pertinent of reports. The design principles of said peptide nanostructures are outlined as well as their functionalization for imaging modalities and tumor targeting. The landscape of the field is explored and areas that were deemed underdeveloped are highlighted. Finally, the challenges and limitations that must be overcome to enable the wider clinical adoption of peptide-based nanomaterials in cancer imaging are discussed, and future perspectives are offered.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"1-20"},"PeriodicalIF":3.9,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146108868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-08DOI: 10.1080/17435889.2025.2598329
Donguk Kim, Augustine Duffy, Alex Wee, Hunter Hammond, Anjali Sangappa, Ravi S Kane
Influenza remains a major global health concern, with the ongoing seasonal epidemics causing millions of cases and up to 650,000 deaths worldwide annually. Current influenza vaccines only provide strain-specific and short-lived protection, exposing vulnerability to antigenic drift and reassortments. To overcome these limitations, next-generation vaccine platforms are being developed, with nanoparticle-based approaches showing promise. Displaying hemagglutinin (HA) on multivalent scaffolds enhances B cell receptor engagement, germinal center formation, and affinity maturation, while supporting durable and broadly protective humoral immunity. This review highlights recent published advances found in PubMed, Web of Science, and Google Scholar since 2020 in HA-displaying nanoparticle influenza vaccines, emphasizing strategies to improve immunogenicity, broaden protection across influenza strains and subtypes, and redirect responses toward conserved epitopes of HA.
流感仍然是一个主要的全球健康问题,持续的季节性流行病每年在全世界造成数百万病例和多达65万人死亡。目前的流感疫苗仅提供毒株特异性和短期保护,暴露了抗原漂移和重组的脆弱性。为了克服这些限制,正在开发下一代疫苗平台,基于纳米颗粒的方法显示出希望。在多价支架上显示血凝素(HA)可以增强B细胞受体的结合、生发中心的形成和亲和成熟,同时支持持久和广泛的保护性体液免疫。本综述重点介绍了自2020年以来在PubMed、Web of Science和谷歌Scholar上发现的显示HA的纳米颗粒流感疫苗的最新进展,强调了提高免疫原性、扩大流感毒株和亚型的保护以及将反应转向HA保守表位的策略。
{"title":"Hemagglutinin-displaying influenza nanovaccines: progress and promise.","authors":"Donguk Kim, Augustine Duffy, Alex Wee, Hunter Hammond, Anjali Sangappa, Ravi S Kane","doi":"10.1080/17435889.2025.2598329","DOIUrl":"10.1080/17435889.2025.2598329","url":null,"abstract":"<p><p>Influenza remains a major global health concern, with the ongoing seasonal epidemics causing millions of cases and up to 650,000 deaths worldwide annually. Current influenza vaccines only provide strain-specific and short-lived protection, exposing vulnerability to antigenic drift and reassortments. To overcome these limitations, next-generation vaccine platforms are being developed, with nanoparticle-based approaches showing promise. Displaying hemagglutinin (HA) on multivalent scaffolds enhances B cell receptor engagement, germinal center formation, and affinity maturation, while supporting durable and broadly protective humoral immunity. This review highlights recent published advances found in PubMed, Web of Science, and Google Scholar since 2020 in HA-displaying nanoparticle influenza vaccines, emphasizing strategies to improve immunogenicity, broaden protection across influenza strains and subtypes, and redirect responses toward conserved epitopes of HA.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"387-408"},"PeriodicalIF":3.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145703030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-23DOI: 10.1080/17435889.2025.2596217
Yuanlin Tang, Yunfeng Lin, Mi Zhou
Infectious diseases remain a major threat to global public health, a challenge further exacerbated by the rapid rise of antimicrobial resistance. In this context, tetrahedral framework nucleic acids (tFNA) have recently gained attention as a novel nanomaterial platform with therapeutic potential. Their advantages arise from a dual mechanism. On one hand, tFNA directly contribute to overcoming antimicrobial resistance by facilitating antibiotic penetration, disrupting bacterial membrane integrity, and downregulating resistance-associated genes. On the other hand, they serve as efficient drug delivery vehicles that enhance the stability, bioavailability, and cellular uptake of antimicrobial agents. Beyond these antibacterial effects, tFNA can also modulate host immunity: their intrinsic anti-inflammatory and antioxidant properties help mitigate excessive inflammation and tissue injury, thereby supporting the restoration of immune homeostasis. Although several challenges still hinder their clinical translation, tFNA represent a novel and versatile platform for infectious disease treatment, offering considerable promise for future therapeutic development.
{"title":"Functionalized framework nucleic acids for the treatment of infectious diseases.","authors":"Yuanlin Tang, Yunfeng Lin, Mi Zhou","doi":"10.1080/17435889.2025.2596217","DOIUrl":"10.1080/17435889.2025.2596217","url":null,"abstract":"<p><p>Infectious diseases remain a major threat to global public health, a challenge further exacerbated by the rapid rise of antimicrobial resistance. In this context, tetrahedral framework nucleic acids (tFNA) have recently gained attention as a novel nanomaterial platform with therapeutic potential. Their advantages arise from a dual mechanism. On one hand, tFNA directly contribute to overcoming antimicrobial resistance by facilitating antibiotic penetration, disrupting bacterial membrane integrity, and downregulating resistance-associated genes. On the other hand, they serve as efficient drug delivery vehicles that enhance the stability, bioavailability, and cellular uptake of antimicrobial agents. Beyond these antibacterial effects, tFNA can also modulate host immunity: their intrinsic anti-inflammatory and antioxidant properties help mitigate excessive inflammation and tissue injury, thereby supporting the restoration of immune homeostasis. Although several challenges still hinder their clinical translation, tFNA represent a novel and versatile platform for infectious disease treatment, offering considerable promise for future therapeutic development.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"467-480"},"PeriodicalIF":3.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-05DOI: 10.1080/17435889.2025.2598337
Angelea Maestas-Olguin, Maya M Dawson, Emily Rhoades Clark, Olivia L Lanier
Utilization of endogenous RNA interference (RNAi) mechanisms via delivery of exogeneous small interfering RNA (siRNA) molecules offers a transformative approach to treatment of disease by enabling sequence specific silencing of mutated gene expression. Nanotechnology-based platforms have enabled delivery of siRNA and have already been clinically validated for intravenous (IV) infusion administration (e.g patisiran). Oral administration of siRNA remains an unmet challenge due to formidable biological barriers in the gastrointestinal (GI) tract. Nanotechnology-enabled strategies for oral siRNA delivery have emerged as a powerful solution to overcoming these biological barriers for effective gene silencing. This review provides a comprehensive overview of GI barriers for siRNA delivery as well as highlights recent advances in nanoparticle platforms for oral siRNA delivery. In addition, this review explores translational considerations and highlights the potential of oral siRNA nanomedicines to reduce dependence on invasive parenteral delivery and costly monoclonal antibody therapies. Together, these advances outline a promising path toward clinically viable, patient-friendly siRNA therapeutics delivered orally. Literature for this review was identified through database searches [University of New Mexico University Libraries, Web of Science, Google Scholar, and PubMed databases April 2025-November 2025] as it related to the oral delivery of nanoparticles, siRNA-loaded nanoparticles, gene therapy, and related nanomedicine delivery strategies.
通过外源性小干扰RNA (siRNA)分子的传递,利用内源性RNA干扰(RNAi)机制,通过实现突变基因表达的序列特异性沉默,为疾病治疗提供了一种变革性的方法。基于纳米技术的平台使siRNA的递送成为可能,并且已经被临床验证用于静脉(IV)输注给药(例如帕西兰)。由于胃肠道(GI)中存在强大的生物屏障,siRNA的口服给药仍然是一个未解决的挑战。纳米技术支持的siRNA口服递送策略已经成为克服这些生物障碍实现有效基因沉默的有力解决方案。这篇综述提供了siRNA递送的胃肠道屏障的全面概述,并强调了用于口服siRNA递送的纳米颗粒平台的最新进展。此外,本综述探讨了翻译方面的考虑,并强调了口服siRNA纳米药物减少对侵入性肠外给药和昂贵的单克隆抗体治疗的依赖的潜力。总之,这些进展勾勒出了一条通向临床可行、患者友好的口服siRNA疗法的有希望的道路。本综述的文献是通过数据库检索[新墨西哥大学图书馆,Web of Science,谷歌Scholar和PubMed数据库2025年4月- 2025年11月]确定的,因为它与纳米颗粒口服递送,sirna负载纳米颗粒,基因治疗和相关纳米药物递送策略有关。
{"title":"Emerging nanotechnology-enabled siRNA oral delivery platforms.","authors":"Angelea Maestas-Olguin, Maya M Dawson, Emily Rhoades Clark, Olivia L Lanier","doi":"10.1080/17435889.2025.2598337","DOIUrl":"10.1080/17435889.2025.2598337","url":null,"abstract":"<p><p>Utilization of endogenous RNA interference (RNAi) mechanisms via delivery of exogeneous small interfering RNA (siRNA) molecules offers a transformative approach to treatment of disease by enabling sequence specific silencing of mutated gene expression. Nanotechnology-based platforms have enabled delivery of siRNA and have already been clinically validated for intravenous (IV) infusion administration (e.g patisiran). Oral administration of siRNA remains an unmet challenge due to formidable biological barriers in the gastrointestinal (GI) tract. Nanotechnology-enabled strategies for oral siRNA delivery have emerged as a powerful solution to overcoming these biological barriers for effective gene silencing. This review provides a comprehensive overview of GI barriers for siRNA delivery as well as highlights recent advances in nanoparticle platforms for oral siRNA delivery. In addition, this review explores translational considerations and highlights the potential of oral siRNA nanomedicines to reduce dependence on invasive parenteral delivery and costly monoclonal antibody therapies. Together, these advances outline a promising path toward clinically viable, patient-friendly siRNA therapeutics delivered orally. Literature for this review was identified through database searches [University of New Mexico University Libraries, Web of Science, Google Scholar, and PubMed databases April 2025-November 2025] as it related to the oral delivery of nanoparticles, siRNA-loaded nanoparticles, gene therapy, and related nanomedicine delivery strategies.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"409-427"},"PeriodicalIF":3.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Formononetin (FMN) is an extracted component of traditional Chinese medicine with anticancer effects, but its poor water solubility and low bioavailability have limited further research and application. Therefore, based on FMN that is the natural antitumor agent, we synthesized a formononetin quantum dots (FMNQDs) for colon cancer therapy, which has the advantages of outstanding water solubility, homogeneous particle size (2.03 ± 1.0 nm), exceptional stability and good intracellular fluorescence imaging effect. The results show that FMNQD exhibits good antitumor activity by inducing mitochondrial-mediated apoptosis, characterized by elevated intracellular reactive oxygen species (ROS) levels, decreased mitochondrial membrane potential (MMP), and modulated expression of Bax and Bcl-2. In vivo validation confirmed FMNQD's significant tumor growth inhibition. The tumor inhibition rate in the 8 mg/kg dose group was as high as 60.06 ± 6.22%. Moreover, blood biochemical analysis suggested a favorable safety profile. This study establishes FMNQDs as a potential therapeutic agent for colon cancer, providing preclinical evidence to support further development of formononetin-based nanomedicines.
{"title":"Formononetin-derived quantum dots suppress colon cancer growth by triggering mitochondrial apoptosis.","authors":"Junfeng Zhang, Yuqing Cui, Chenchen Li, Tongjin Yin, Min Xu, Hongliang Bian","doi":"10.1080/17435889.2026.2615097","DOIUrl":"10.1080/17435889.2026.2615097","url":null,"abstract":"<p><p>Formononetin (FMN) is an extracted component of traditional Chinese medicine with anticancer effects, but its poor water solubility and low bioavailability have limited further research and application. Therefore, based on FMN that is the natural antitumor agent, we synthesized a formononetin quantum dots (FMNQDs) for colon cancer therapy, which has the advantages of outstanding water solubility, homogeneous particle size (2.03 ± 1.0 nm), exceptional stability and good intracellular fluorescence imaging effect. The results show that FMNQD exhibits good antitumor activity by inducing mitochondrial-mediated apoptosis, characterized by elevated intracellular reactive oxygen species (ROS) levels, decreased mitochondrial membrane potential (MMP), and modulated expression of Bax and Bcl-2. In <i>vivo</i> validation confirmed FMNQD's significant tumor growth inhibition. The tumor inhibition rate in the 8 mg/kg dose group was as high as 60.06 ± 6.22%. Moreover, blood biochemical analysis suggested a favorable safety profile. This study establishes FMNQDs as a potential therapeutic agent for colon cancer, providing preclinical evidence to support further development of formononetin-based nanomedicines.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"485-497"},"PeriodicalIF":3.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145960802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-11DOI: 10.1080/17435889.2025.2599400
Jing Yang, Qing Ji, Wenrong Zhu, Yiming Geng, Baoding Chen
While remarkable strides have been made in personalized precision oncology, integrating diagnosis and therapy within a unitary theranostic platform remains a pivotal challenge. Sonodynamic therapy (SDT), which leverages ultrasound to activate sonosensitizers for generating tumoricidal reactive oxygen species (ROS), offers distinct advantages including non-invasiveness, spatiotemporal precision, and deep tissue penetration. Its capability to visualize tumors by converting acoustic signals into diagnostic images presents a further unique merit. However, SDT efficacy is constrained by suboptimal sonosensitizer efficiency, the hypoxic tumor microenvironment, and augmented antioxidant defenses. Single-atom nanozymes (SANs) emerge as a transformative strategy to overcome these hurdles. They catalytically decompose endogenous hydrogen peroxide to alleviate hypoxia, deplete glutathione to disarm antioxidant defenses, and harness piezoelectric synergies. The integration of SANs' atomic-level catalytic architecture with sonosensitizers' ultrasonic responsiveness facilitates tumor hypoxia mitigation and enables image-guided precision therapy. This review systematically elucidates the molecular design of SAN-based sonosensitizers, analyzes their catalytic mechanisms for enhancing SDT, and discusses associated challenges and future directions for clinical translation. It aims to lay a theoretical foundation for developing next-generation sonodynamic SANs that are intelligent, safe, and environmentally benign. [PubMed and Web of Science, from inception to June 2025].
虽然在个性化精准肿瘤学方面取得了显著的进步,但在统一的治疗平台内整合诊断和治疗仍然是一个关键的挑战。声动力疗法(SDT)利用超声波激活声敏剂产生杀肿瘤活性氧(ROS),具有非侵入性、时空精确性和深层组织穿透性等明显优势。它通过将声学信号转换成诊断图像来可视化肿瘤的能力显示出另一个独特的优点。然而,SDT的疗效受到次优声敏剂效率、低氧肿瘤微环境和增强抗氧化防御的限制。单原子纳米酶(SANs)的出现是克服这些障碍的一种变革性策略。它们催化分解内源性过氧化氢以缓解缺氧,消耗谷胱甘肽以解除抗氧化防御,并利用压电协同作用。SANs的原子级催化结构与超声敏化剂的超声响应性相结合,有助于缓解肿瘤缺氧,实现图像引导的精确治疗。本文系统地阐述了基于san的声敏剂的分子设计,分析了其增强SDT的催化机制,并讨论了相关的挑战和临床转化的未来方向。其目的是为开发智能、安全、环保的下一代声动力san奠定理论基础。[PubMed和Web of Science,从创立到2025年6月]。
{"title":"Augmenting sonodynamic therapy with single-atom nanoenzyme via tumor microenvironment-mediated reactive oxygen species generation.","authors":"Jing Yang, Qing Ji, Wenrong Zhu, Yiming Geng, Baoding Chen","doi":"10.1080/17435889.2025.2599400","DOIUrl":"10.1080/17435889.2025.2599400","url":null,"abstract":"<p><p>While remarkable strides have been made in personalized precision oncology, integrating diagnosis and therapy within a unitary theranostic platform remains a pivotal challenge. Sonodynamic therapy (SDT), which leverages ultrasound to activate sonosensitizers for generating tumoricidal reactive oxygen species (ROS), offers distinct advantages including non-invasiveness, spatiotemporal precision, and deep tissue penetration. Its capability to visualize tumors by converting acoustic signals into diagnostic images presents a further unique merit. However, SDT efficacy is constrained by suboptimal sonosensitizer efficiency, the hypoxic tumor microenvironment, and augmented antioxidant defenses. Single-atom nanozymes (SANs) emerge as a transformative strategy to overcome these hurdles. They catalytically decompose endogenous hydrogen peroxide to alleviate hypoxia, deplete glutathione to disarm antioxidant defenses, and harness piezoelectric synergies. The integration of SANs' atomic-level catalytic architecture with sonosensitizers' ultrasonic responsiveness facilitates tumor hypoxia mitigation and enables image-guided precision therapy. This review systematically elucidates the molecular design of SAN-based sonosensitizers, analyzes their catalytic mechanisms for enhancing SDT, and discusses associated challenges and future directions for clinical translation. It aims to lay a theoretical foundation for developing next-generation sonodynamic SANs that are intelligent, safe, and environmentally benign. [PubMed and Web of Science, from inception to June 2025].</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"629-642"},"PeriodicalIF":3.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-17DOI: 10.1080/17435889.2025.2602649
Helmut Spielvogel, Rainer Tietze, Stefan Lyer, Christina Janko, Teresa Siegert, Iwona Cicha, Christoph Alexiou
Whenever nanomaterials come into contact with cells and tissues, the risk of material-specific cytotoxic reaction is increased. With the widespread use of nanoparticles in industrial, but also biomedical applications, the increasing exposure to nanomaterials raises safety concerns. In-depth understanding the mechanisms of nanomaterial interactions with cells and of their cytotoxic effects is therefore important both for minimizing the risk of potential adverse effects on human health in case of involuntary exposure and for enhancing cell-killing ability of nanosystems developed as tumoritoxic tools. This Journal Watch article highlights recent reports focusing on mechanisms of cellular interactions and toxicity of nanomaterials.
{"title":"New insights into the mechanisms of cellular interactions and toxicity of nanomaterials.","authors":"Helmut Spielvogel, Rainer Tietze, Stefan Lyer, Christina Janko, Teresa Siegert, Iwona Cicha, Christoph Alexiou","doi":"10.1080/17435889.2025.2602649","DOIUrl":"10.1080/17435889.2025.2602649","url":null,"abstract":"<p><p>Whenever nanomaterials come into contact with cells and tissues, the risk of material-specific cytotoxic reaction is increased. With the widespread use of nanoparticles in industrial, but also biomedical applications, the increasing exposure to nanomaterials raises safety concerns. In-depth understanding the mechanisms of nanomaterial interactions with cells and of their cytotoxic effects is therefore important both for minimizing the risk of potential adverse effects on human health in case of involuntary exposure and for enhancing cell-killing ability of nanosystems developed as tumoritoxic tools. This Journal Watch article highlights recent reports focusing on mechanisms of cellular interactions and toxicity of nanomaterials.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"327-330"},"PeriodicalIF":3.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}