Pub Date : 2024-12-01Epub Date: 2024-01-12DOI: 10.1080/1061186X.2023.2295220
Danni Zhu, Yao Li, Jinlong Zhang, Yi Chen, Xiaohong Song, Wei Chen, Shipo Wu, Lihua Hou
Aims: Nerve growth factor is a well characterised neurotrophic factor that play a critical role in the survival, growth and differentiation of neurons both in central and peripheral nervous system. However, it is difficult for the conventional exogenous nerve growth factor administration delivery to the central nervous system due to the biological barrier in human bodies.Results: We validated a series of cell penetrating peptides and found that L-PenetraMax significantly enhanced the efficiency of recombinant human nerve growth factor entry into the rat retina. In the optic nerve crush mice model, eye drop administration of recombinant human nerve growth factor alone promoted retinal ganglion cell survival and axon regeneration at high dose, while the combination of recombinant human nerve growth factor with L-PenetraMax significantly enhanced the neuroprotective efficacy at lower dose, thus potentially enhancing the availability of recombinant human nerve growth factor eye drops in patients with optic neuropathy.Conclusions: This study provides the evidence that the noncovalent coadministration of recombinant human nerve growth factor with L-PenetraMax could be a potent strategy for the non-invasive and sustained ocular delivery of therapeutic proteins for improving the optic nerve injury.
{"title":"Enhanced neuroprotective activity of ophthalmic delivered nerve growth factor conjugated with cell penetrating peptide against optic nerve injury.","authors":"Danni Zhu, Yao Li, Jinlong Zhang, Yi Chen, Xiaohong Song, Wei Chen, Shipo Wu, Lihua Hou","doi":"10.1080/1061186X.2023.2295220","DOIUrl":"10.1080/1061186X.2023.2295220","url":null,"abstract":"<p><p><b>Aims:</b> Nerve growth factor is a well characterised neurotrophic factor that play a critical role in the survival, growth and differentiation of neurons both in central and peripheral nervous system. However, it is difficult for the conventional exogenous nerve growth factor administration delivery to the central nervous system due to the biological barrier in human bodies.<b>Results:</b> We validated a series of cell penetrating peptides and found that L-PenetraMax significantly enhanced the efficiency of recombinant human nerve growth factor entry into the rat retina. In the optic nerve crush mice model, eye drop administration of recombinant human nerve growth factor alone promoted retinal ganglion cell survival and axon regeneration at high dose, while the combination of recombinant human nerve growth factor with L-PenetraMax significantly enhanced the neuroprotective efficacy at lower dose, thus potentially enhancing the availability of recombinant human nerve growth factor eye drops in patients with optic neuropathy.<b>Conclusions:</b> This study provides the evidence that the noncovalent coadministration of recombinant human nerve growth factor with L-PenetraMax could be a potent strategy for the non-invasive and sustained ocular delivery of therapeutic proteins for improving the optic nerve injury.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138804190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1080/1061186X.2024.2373304
Carolini Mendes, Rubya Pereira Zaccaron, Laura de Roch Casagrande, Ligia Milanez Venturini, Camila da Costa, Igor Ramos Lima, Tiago Bender Wermuth, Sabrina Arcaro, Paulo Emilio Feuser, Paulo Cesar Lock Silvira
Cost-effective strategies for the treatment of chronic wounds must be developed. The green synthesis of gold nanoparticles (GNPs) it is possible to guarantee a lower toxicity in biological tissues and greater safety of applicability, in addition to adding the effects of nanoparticles (NPs) to those of extracts. The objective of this study was to evaluate the effects of treatment with biosynthesized GNPs in a chronic wound model. Wistar rats were distributed into 7 groups: Acute Wound (AW); Chronic wound (CW); CW + GNPs-Açaí; CW + GNPs-DB; CW + AV-GNPs; CW + SafGel®; CW + 660 nm laser. The chronic injury model was induced with topically applied Resiquimod for 6 days. Treatments were then initated on the fourteenth day after the last application of Resiquimod and carried out daily for ten days. The proposed therapies with GNPs were able to significantly reduce the inflammatory score and increase the rate of wound contraction. In histology, there was a reduction in the inflammatory infiltrate and increased gene expression of fibronectin and type III collagen, mainly in the CW + AV-GNPs group. The therapies were able to reduce pro-inflammatory cytokines, increase anti-inflammatory cytokines, and reduce oxidative stress. The results demonstrated that the effects of GNPs appear to complement those of the extracts, thereby enhancing the tissue repair process.
{"title":"Green synthesis of gold nanoparticles in an animal model of chronic wound induced with Resiquimod.","authors":"Carolini Mendes, Rubya Pereira Zaccaron, Laura de Roch Casagrande, Ligia Milanez Venturini, Camila da Costa, Igor Ramos Lima, Tiago Bender Wermuth, Sabrina Arcaro, Paulo Emilio Feuser, Paulo Cesar Lock Silvira","doi":"10.1080/1061186X.2024.2373304","DOIUrl":"https://doi.org/10.1080/1061186X.2024.2373304","url":null,"abstract":"<p><p>Cost-effective strategies for the treatment of chronic wounds must be developed. The green synthesis of gold nanoparticles (GNPs) it is possible to guarantee a lower toxicity in biological tissues and greater safety of applicability, in addition to adding the effects of nanoparticles (NPs) to those of extracts. The objective of this study was to evaluate the effects of treatment with biosynthesized GNPs in a chronic wound model. Wistar rats were distributed into 7 groups: Acute Wound (AW); Chronic wound (CW); CW + GNPs-Açaí; CW + GNPs-DB; CW + AV-GNPs; CW + SafGel®; CW + 660 nm laser. The chronic injury model was induced with topically applied Resiquimod for 6 days. Treatments were then initated on the fourteenth day after the last application of Resiquimod and carried out daily for ten days. The proposed therapies with GNPs were able to significantly reduce the inflammatory score and increase the rate of wound contraction. In histology, there was a reduction in the inflammatory infiltrate and increased gene expression of fibronectin and type III collagen, mainly in the CW + AV-GNPs group. The therapies were able to reduce pro-inflammatory cytokines, increase anti-inflammatory cytokines, and reduce oxidative stress. The results demonstrated that the effects of GNPs appear to complement those of the extracts, thereby enhancing the tissue repair process.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1080/1061186X.2024.2374034
Hayrettin Tonbul, Adem Şahin, Süleyman Can Öztürk, Gözde Ultav, Ece Tavukçuoğlu, Sedenay Akbaş, Yeşim Aktaş, Güneş Esendağlı, Yılmaz Çapan
Overexpression of permeability-glycoprotein (P-gp) transporter leads to multidrug resistance (MDR) through cellular exclusion of chemotherapeutics. Co-administration of P-gp inhibitors and chemotherapeutics is a promising approach for improving the efficacy of therapy. Nevertheless, problems in pharmacokinetics, toxicity and solubility limit the application of P-gp inhibitors. Herein, we developed a novel all-in-one hybrid nanoparticle system to overcome MDR in doxorubicin (DOX)-resistant breast cancer. First, folic acid-modified DOX-loaded mesoporous silica nanoparticles (MSNs) were prepared and then loaded into PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles along with a P-gp inhibitor, elacridar. This hybrid nanoparticle system had high drug loading capacity, enabled both passive and active targeting of tumour tissues, and exhibited sequential and pH-triggered release of drugs. In vitro and in vivo studies in DOX-resistant breast cancer demonstrated the ability of the hybrid nanoparticles to reverse P-gp-mediated drug resistance. The nanoparticles were efficiently taken up by the breast cancer cells and delivered elacridar, in vitro. Biodistribution studies demonstrated substantial accumulation of the folate receptor-targeted PLGA/MSN hybrid nanoparticles in tumour-bearing mice. Moreover, deceleration of the tumour growth was remarkable in the animals administered with the DOX and elacridar co-loaded hybrid nanoparticles when compared to those treated with the marketed liposomal DOX (Caelyx®) or its combination with elacridar.
{"title":"An all-in-one nanoparticle for overcoming drug resistance: doxorubicin and elacridar co-loaded folate receptor targeted PLGA/MSN hybrid nanoparticles.","authors":"Hayrettin Tonbul, Adem Şahin, Süleyman Can Öztürk, Gözde Ultav, Ece Tavukçuoğlu, Sedenay Akbaş, Yeşim Aktaş, Güneş Esendağlı, Yılmaz Çapan","doi":"10.1080/1061186X.2024.2374034","DOIUrl":"10.1080/1061186X.2024.2374034","url":null,"abstract":"<p><p>Overexpression of permeability-glycoprotein (P-gp) transporter leads to multidrug resistance (MDR) through cellular exclusion of chemotherapeutics. Co-administration of P-gp inhibitors and chemotherapeutics is a promising approach for improving the efficacy of therapy. Nevertheless, problems in pharmacokinetics, toxicity and solubility limit the application of P-gp inhibitors. Herein, we developed a novel all-in-one hybrid nanoparticle system to overcome MDR in doxorubicin (DOX)-resistant breast cancer. First, folic acid-modified DOX-loaded mesoporous silica nanoparticles (MSNs) were prepared and then loaded into PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles along with a P-gp inhibitor, elacridar. This hybrid nanoparticle system had high drug loading capacity, enabled both passive and active targeting of tumour tissues, and exhibited sequential and pH-triggered release of drugs. <i>In vitro</i> and <i>in vivo</i> studies in DOX-resistant breast cancer demonstrated the ability of the hybrid nanoparticles to reverse P-gp-mediated drug resistance. The nanoparticles were efficiently taken up by the breast cancer cells and delivered elacridar, <i>in vitro</i>. Biodistribution studies demonstrated substantial accumulation of the folate receptor-targeted PLGA/MSN hybrid nanoparticles in tumour-bearing mice. Moreover, deceleration of the tumour growth was remarkable in the animals administered with the DOX and elacridar co-loaded hybrid nanoparticles when compared to those treated with the marketed liposomal DOX (Caelyx<sup>®</sup>) or its combination with elacridar.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The discovery of novel targeted agents for non-small cell lung cancer (NSCLC) remains an important research landscape due to the limited efficacy, side effects and drug resistance of current treatment options. Among many repurposed drugs, disulfiram (DSF) has shown the potential to target tumors. However, its unpleasant neurotoxicity greatly limits its use. A DSF derivative, S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine (DS-NAC), was synthesized against NSCLC. The therapeutic effects, mechanism, and toxicities of DS-NAC were evaluated in A549 and H460 cells and the mouse model of in-situ lung cancer. The in-vitro results exhibited that DS-NAC had potent anti-proliferation, apoptotic, anti-metastasis, and epithelial-mesenchymal transition (EMT) inhibition effects. In the orthotopic lung cancer mouse model, therapeutic effects of DS-NAC were better than that of DSF and were similar to docetaxel (DTX). Also, results from western blot and immunohistochemistry showed that DS-NAC in combination with copper exerted the therapeutic effects via regulating NF-κB signaling pathway and ROS-related proteins such as HIF-1α, Nrf2, and PKC-δ rather than regulating ROS level directly. Moreover, the safety evaluation study showed that DS-NAC had low hematologic and hepatic toxicities in comparision with DTX as well as low neurological toxicity compared with DSF. DS-NAC could be a promising anti-lung cancer agent with a favorable safety profile.
{"title":"S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine for the Treatment of Non-Small Cell Lung Cancer through Regulating NF-κB Signaling Pathway without Neurotoxicity.","authors":"Huaiyou Lv, Huatian Yang, Yifei Duan, Chongzheng Yan, Genju Li, Guozhi Zhao, Fengqin Sun, Yafei Feng, Yuhan Li, Yaqing Fu, Yizhe Li, Zhongxi Zhao, Xiumei Jia","doi":"10.1080/1061186X.2024.2374037","DOIUrl":"https://doi.org/10.1080/1061186X.2024.2374037","url":null,"abstract":"<p><p>The discovery of novel targeted agents for non-small cell lung cancer (NSCLC) remains an important research landscape due to the limited efficacy, side effects and drug resistance of current treatment options. Among many repurposed drugs, disulfiram (DSF) has shown the potential to target tumors. However, its unpleasant neurotoxicity greatly limits its use. A DSF derivative, S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine (DS-NAC), was synthesized against NSCLC. The therapeutic effects, mechanism, and toxicities of DS-NAC were evaluated in A549 and H460 cells and the mouse model of <i>in-situ</i> lung cancer. The <i>in-vitro</i> results exhibited that DS-NAC had potent anti-proliferation, apoptotic, anti-metastasis, and epithelial-mesenchymal transition (EMT) inhibition effects. In the orthotopic lung cancer mouse model, therapeutic effects of DS-NAC were better than that of DSF and were similar to docetaxel (DTX). Also, results from western blot and immunohistochemistry showed that DS-NAC in combination with copper exerted the therapeutic effects via regulating NF-κB signaling pathway and ROS-related proteins such as HIF-1α, Nrf2, and PKC-δ rather than regulating ROS level directly. Moreover, the safety evaluation study showed that DS-NAC had low hematologic and hepatic toxicities in comparision with DTX as well as low neurological toxicity compared with DSF. DS-NAC could be a promising anti-lung cancer agent with a favorable safety profile.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1080/1061186X.2024.2372316
Wendi Yan, Yang Zhang, Yuxiang Dai, Junbo Ge
Pan-vascular diseases, based on systems biology theory, explore the commonalities and individualities of important target organs such as cardiovascular, cerebrovascular and peripheral blood vessels, starting from the systemic and holistic aspects of vascular diseases. The purpose is to understand the interrelationships and results between them, achieve vascular health or sub-health, and comprehensively improve the physical and mental health of the entire population. Post-translational modification (PTM) is an important part of epigenetics, including phosphorylation, acetylation, ubiquitination, methylation, etc., playing a crucial role in the pan-vascular system. Crotonylation is a novel type of PTM that has made significant progress in the research of pan-vascular related diseases in recent years. Based on the review of previous studies, this article summarises the various regulatory factors of crotonylation, physiological functions and the mechanisms of histone and non-histone crotonylation in regulating pan-vascular related diseases to explore the possibility of precise regulation of crotonylation sites as potential targets for disease treatment and the value of clinical translation.
{"title":"Application of crotonylation modification in pan-vascular diseases.","authors":"Wendi Yan, Yang Zhang, Yuxiang Dai, Junbo Ge","doi":"10.1080/1061186X.2024.2372316","DOIUrl":"10.1080/1061186X.2024.2372316","url":null,"abstract":"<p><p>Pan-vascular diseases, based on systems biology theory, explore the commonalities and individualities of important target organs such as cardiovascular, cerebrovascular and peripheral blood vessels, starting from the systemic and holistic aspects of vascular diseases. The purpose is to understand the interrelationships and results between them, achieve vascular health or sub-health, and comprehensively improve the physical and mental health of the entire population. Post-translational modification (PTM) is an important part of epigenetics, including phosphorylation, acetylation, ubiquitination, methylation, etc., playing a crucial role in the pan-vascular system. Crotonylation is a novel type of PTM that has made significant progress in the research of pan-vascular related diseases in recent years. Based on the review of previous studies, this article summarises the various regulatory factors of crotonylation, physiological functions and the mechanisms of histone and non-histone crotonylation in regulating pan-vascular related diseases to explore the possibility of precise regulation of crotonylation sites as potential targets for disease treatment and the value of clinical translation.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-03DOI: 10.1080/1061186X.2024.2369876
Shuyi Zhang, Guangyao Li, Kewen Qian, Yitan Zou, Xinya Zheng, Hongru Ai, Fangxing Lin, Changhai Lei, Shi Hu
Exosome therapy has garnered significant attention due to its natural delivery capabilities, low toxicity, high biocompatibility, and potential for personalised treatment through engineering modifications. Recent studies have highlighted the ability of tumour cell-derived exosomes (TDEs) to interact with immune cells or modify the immune microenvironment to suppress host immune responses, as well as their unique homing ability to parental cells. The core question of this study is whether this immunomodulatory property of TDEs can be utilised for the immunotherapy of inflammatory diseases. In our experiments, we prepared exosomes derived from murine colon cancer cells CT26 (CT26 exo) using ultracentrifugation, characterised them, and conducted proteomic analysis. The therapeutic potential of CT26 exo was evaluated in our dextran sulphate sodium salt (DSS)-induced inflammatory bowel disease (IBD) mouse model. Compared to the control and 293 T exo treatment groups, mice treated with CT26 exo showed a reduction in the disease activity index (DAI) and colon shortening rate, with no noticeable weight loss. Haematoxylin and eosin (H&E) staining of colon paraffin sections revealed reduced inflammatory infiltration and increased epithelial goblet cells in the colons of CT26 exo-treated group. Furthermore, we conducted preliminary mechanistic explorations by examining the phenotyping and function of CD4+ T cells and dendritic cells (DCs) in the colonic lamina propria of mice. The results indicated that the ameliorative effect of CT26 exosomes might be due to their inhibition of pro-inflammatory cytokine secretion by colonic DCs and selective suppression of Th17 cell differentiation in the colon. Additionally, CT26 exo exhibited good biosafety. Our findings propose a novel exosome-based therapeutic approach for IBD and suggest the potential application of TDEs in the treatment of inflammatory diseases.
{"title":"Exosomes derived from cancer cells relieve inflammatory bowel disease in mice.","authors":"Shuyi Zhang, Guangyao Li, Kewen Qian, Yitan Zou, Xinya Zheng, Hongru Ai, Fangxing Lin, Changhai Lei, Shi Hu","doi":"10.1080/1061186X.2024.2369876","DOIUrl":"https://doi.org/10.1080/1061186X.2024.2369876","url":null,"abstract":"<p><p>Exosome therapy has garnered significant attention due to its natural delivery capabilities, low toxicity, high biocompatibility, and potential for personalised treatment through engineering modifications. Recent studies have highlighted the ability of tumour cell-derived exosomes (TDEs) to interact with immune cells or modify the immune microenvironment to suppress host immune responses, as well as their unique homing ability to parental cells. The core question of this study is whether this immunomodulatory property of TDEs can be utilised for the immunotherapy of inflammatory diseases. In our experiments, we prepared exosomes derived from murine colon cancer cells CT26 (CT26 exo) using ultracentrifugation, characterised them, and conducted proteomic analysis. The therapeutic potential of CT26 exo was evaluated in our dextran sulphate sodium salt (DSS)-induced inflammatory bowel disease (IBD) mouse model. Compared to the control and 293 T exo treatment groups, mice treated with CT26 exo showed a reduction in the disease activity index (DAI) and colon shortening rate, with no noticeable weight loss. Haematoxylin and eosin (H&E) staining of colon paraffin sections revealed reduced inflammatory infiltration and increased epithelial goblet cells in the colons of CT26 exo-treated group. Furthermore, we conducted preliminary mechanistic explorations by examining the phenotyping and function of CD4<sup>+</sup> T cells and dendritic cells (DCs) in the colonic lamina propria of mice. The results indicated that the ameliorative effect of CT26 exosomes might be due to their inhibition of pro-inflammatory cytokine secretion by colonic DCs and selective suppression of Th17 cell differentiation in the colon. Additionally, CT26 exo exhibited good biosafety. Our findings propose a novel exosome-based therapeutic approach for IBD and suggest the potential application of TDEs in the treatment of inflammatory diseases.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-03DOI: 10.1080/1061186X.2024.2373306
Debarpan Chatterjee, Srijan Bhattacharya, Leena Kumari, Aparna Datta
Glioblastoma, a formidable brain cancer, has remained a therapeutic challenge due to its aggressive nature and resistance to conventional treatments. Recent data indicate that aptamers, short synthetic DNA or RNA molecules can be used in anti-cancer therapy due to their better tumour penetration, specific binding affinity, longer retention in tumour sites and their ability to cross the blood-brain barrier. With the ability to modify these oligonucleotides through the selection process, and using rational design to modify them, post-SELEX aptamers offer several advantages in glioblastoma treatment, including precise targeting of cancer cells while sparing healthy tissue. This review discusses the pivotal role of aptamers in glioblastoma therapy and diagnosis, emphasising their potential to enhance treatment efficacy and also highlights recent advancements in aptamer-based therapies which can transform the landscape of glioblastoma treatment, offering renewed hope to patients and clinicians alike.
胶质母细胞瘤是一种可怕的脑癌,由于其侵袭性和对传统疗法的抗药性,一直是治疗上的难题。最新数据表明,aptamers(短合成 DNA 或 RNA 分子)具有更好的肿瘤穿透性、特异性结合亲和力、在肿瘤部位保留时间更长以及穿越血脑屏障的能力,因此可用于抗癌治疗。由于可以通过选择过程对这些寡核苷酸进行修饰,并利用合理的设计对其进行修饰,后SELEX适配体在胶质母细胞瘤治疗中具有多种优势,包括精确靶向癌细胞,同时不损伤健康组织。这篇综述讨论了适配体在胶质母细胞瘤治疗和诊断中的关键作用,强调了它们在提高疗效方面的潜力,还重点介绍了基于适配体的疗法的最新进展,这些疗法可以改变胶质母细胞瘤治疗的格局,为患者和临床医生带来新的希望。
{"title":"Aptamers: ushering in new hopes in targeted glioblastoma therapy.","authors":"Debarpan Chatterjee, Srijan Bhattacharya, Leena Kumari, Aparna Datta","doi":"10.1080/1061186X.2024.2373306","DOIUrl":"10.1080/1061186X.2024.2373306","url":null,"abstract":"<p><p>Glioblastoma, a formidable brain cancer, has remained a therapeutic challenge due to its aggressive nature and resistance to conventional treatments. Recent data indicate that aptamers, short synthetic DNA or RNA molecules can be used in anti-cancer therapy due to their better tumour penetration, specific binding affinity, longer retention in tumour sites and their ability to cross the blood-brain barrier. With the ability to modify these oligonucleotides through the selection process, and using rational design to modify them, post-SELEX aptamers offer several advantages in glioblastoma treatment, including precise targeting of cancer cells while sparing healthy tissue. This review discusses the pivotal role of aptamers in glioblastoma therapy and diagnosis, emphasising their potential to enhance treatment efficacy and also highlights recent advancements in aptamer-based therapies which can transform the landscape of glioblastoma treatment, offering renewed hope to patients and clinicians alike.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1080/1061186X.2024.2367563
Clelia Di Salvo, Vanessa D'Antongiovanni, Laura Benvenuti, Matteo Fornai, Giulia Valdiserra, Gianfranco Natale, Larisa Ryskalin, Elena Lucarini, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Rocchina Colucci, György Haskó, Carolina Pellegrini, Luca Antonioli
Nowadays, the pharmacological management of visceral hypersensitivity associated with colitis is ineffective. In this context, targeting purinergic P2X4 receptor (P2X4R), which can modulate visceral pain transmission, could represent a promising therapeutic strategy. Herein, we tested the pain-relieving effect of two novel and selective P2X4R antagonists (NC-2600 and NP-1815-PX) in a murine model of DNBS-induced colitis and investigated the mechanisms underlying their effect. Tested drugs and dexamethasone (DEX) were administered orally, two days after colitis induction. Treatment with tested drugs and DEX improved tissue inflammatory parameters (body weight, spleen weight, macroscopic damage, TNF and IL-1β levels) in DNBS-rats. In addition, NC-2600 and NP-1815-PX attenuated visceral pain better than DEX and prevented the reduction of occludin expression. In in vitro studies, treatment of CaCo2 cells with supernatant from THP-1 cells, previously treated with LPS plus ATP, reduced the expression of tight junctions protein. By contrast, CaCo2 cells treated with supernatant from THP-1 cells, previously incubated with tested drugs, counteracted the reduction of tight junctions due to the inhibition of P2X4R/NLRP3/IL-1β axis. In conclusion, these results suggest that the direct and selective inhibition of P2X4R represents a viable approach for the management of visceral pain associated with colitis via NLRP3/IL-1β axis inhibition.
{"title":"The pharmacological blockade of P2X4 receptor as a viable approach to manage visceral pain in a rat model of colitis.","authors":"Clelia Di Salvo, Vanessa D'Antongiovanni, Laura Benvenuti, Matteo Fornai, Giulia Valdiserra, Gianfranco Natale, Larisa Ryskalin, Elena Lucarini, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Rocchina Colucci, György Haskó, Carolina Pellegrini, Luca Antonioli","doi":"10.1080/1061186X.2024.2367563","DOIUrl":"10.1080/1061186X.2024.2367563","url":null,"abstract":"<p><p>Nowadays, the pharmacological management of visceral hypersensitivity associated with colitis is ineffective. In this context, targeting purinergic P2X4 receptor (P2X4R), which can modulate visceral pain transmission, could represent a promising therapeutic strategy. Herein, we tested the pain-relieving effect of two novel and selective P2X4R antagonists (NC-2600 and NP-1815-PX) in a murine model of DNBS-induced colitis and investigated the mechanisms underlying their effect. Tested drugs and dexamethasone (DEX) were administered orally, two days after colitis induction. Treatment with tested drugs and DEX improved tissue inflammatory parameters (body weight, spleen weight, macroscopic damage, TNF and IL-1β levels) in DNBS-rats. In addition, NC-2600 and NP-1815-PX attenuated visceral pain better than DEX and prevented the reduction of occludin expression. In <i>in vitro</i> studies, treatment of CaCo2 cells with supernatant from THP-1 cells, previously treated with LPS plus ATP, reduced the expression of tight junctions protein. By contrast, CaCo2 cells treated with supernatant from THP-1 cells, previously incubated with tested drugs, counteracted the reduction of tight junctions due to the inhibition of P2X4R/NLRP3/IL-1β axis. In conclusion, these results suggest that the direct and selective inhibition of P2X4R represents a viable approach for the management of visceral pain associated with colitis <i>via</i> NLRP3/IL-1β axis inhibition.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-05-30DOI: 10.1080/1061186X.2024.2352757
Chenglong Li, Yan Li, Qing Zeng, Yang Zhou, Huaiyu Su, Yangyun Han, Chen Li
Rheumatoid arthritis (RA) is a chronic autoimmune inflammation. Excessive proliferation and inadequate apoptosis of synovial macrophages are the crucial events of RA. Therefore, delivering therapeutic molecules to synovial macrophages specifically to tackle apoptotic insufficiency probably can be an efficient way to reduce joint inflammation and bone erosion. Based on the characteristics of dextran sulphate (DS) specifically binding scavenger receptor A (SR-A) on macrophage and celastrol (CLT) inducing apoptosis, we designed synovial macrophage-targeted nano-emulsions encapsulated with CLT (SR-CLTNEs) and explored their anti-RA effect. After intravenous injection, fluorescence-labelled SR-CLTNEs successfully targeted inflammatory joints and synovial macrophages in a mouse model of RA, with the macrophage targeting efficiency of SR-CLTNEs, CLTNEs and free DID was 20.53%, 13.93% and 9.8%, respectively. In vivo and in vitro studies showed that SR-CLTNEs effectively promoted the apoptosis of macrophages, reshaped the balance between apoptosis and proliferation, and ultimately treated RA in a high efficiency and low toxicity manner. Overall, our work demonstrates the efficacy of using SR-CLTNEs as a novel nanotherapeutic approach for RA therapy and the great translational potential of SR-CLTNEs.
{"title":"Celastrol nano-emulsions selectively regulate apoptosis of synovial macrophage for alleviating rheumatoid arthritis.","authors":"Chenglong Li, Yan Li, Qing Zeng, Yang Zhou, Huaiyu Su, Yangyun Han, Chen Li","doi":"10.1080/1061186X.2024.2352757","DOIUrl":"10.1080/1061186X.2024.2352757","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune inflammation. Excessive proliferation and inadequate apoptosis of synovial macrophages are the crucial events of RA. Therefore, delivering therapeutic molecules to synovial macrophages specifically to tackle apoptotic insufficiency probably can be an efficient way to reduce joint inflammation and bone erosion. Based on the characteristics of dextran sulphate (DS) specifically binding scavenger receptor A (SR-A) on macrophage and celastrol (CLT) inducing apoptosis, we designed synovial macrophage-targeted nano-emulsions encapsulated with CLT (SR-CLTNEs) and explored their anti-RA effect. After intravenous injection, fluorescence-labelled SR-CLTNEs successfully targeted inflammatory joints and synovial macrophages in a mouse model of RA, with the macrophage targeting efficiency of SR-CLTNEs, CLTNEs and free DID was 20.53%, 13.93% and 9.8%, respectively. <i>In vivo</i> and <i>in vitro</i> studies showed that SR-CLTNEs effectively promoted the apoptosis of macrophages, reshaped the balance between apoptosis and proliferation, and ultimately treated RA in a high efficiency and low toxicity manner. Overall, our work demonstrates the efficacy of using SR-CLTNEs as a novel nanotherapeutic approach for RA therapy and the great translational potential of SR-CLTNEs.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recent advances in the field of drug delivery have opened new avenues for the development of novel nanodrug delivery systems (NDDS) in cancer therapy. Self-assembled nanoparticles (SANPs) based on tumour microenvironment have great advantages in improving antitumor effect, and pH-responsive SANPs prepared by the combination of pH-responsive nanomaterials and self-assembly technology can effectively improve the efficacy and reduce the systemic toxicity of antitumor drugs. In this review, we describe the characteristics of self-assembly and its driving force, the mechanism of pH-responsive NDDS, and the nanomaterials for pH-responsive SANPs type. A series of pH-responsive SANPs for tumour-targeted drug delivery are discussed, with an emphasis on the relation between structural features and theranostic performance.
{"title":"pH-responsive self-assembled nanoparticles for tumor-targeted drug delivery.","authors":"Henglai Sun, Xinyu Li, Qian Liu, Huagang Sheng, Liqiao Zhu","doi":"10.1080/1061186X.2024.2349124","DOIUrl":"10.1080/1061186X.2024.2349124","url":null,"abstract":"<p><p>Recent advances in the field of drug delivery have opened new avenues for the development of novel nanodrug delivery systems (NDDS) in cancer therapy. Self-assembled nanoparticles (SANPs) based on tumour microenvironment have great advantages in improving antitumor effect, and pH-responsive SANPs prepared by the combination of pH-responsive nanomaterials and self-assembly technology can effectively improve the efficacy and reduce the systemic toxicity of antitumor drugs. In this review, we describe the characteristics of self-assembly and its driving force, the mechanism of pH-responsive NDDS, and the nanomaterials for pH-responsive SANPs type. A series of pH-responsive SANPs for tumour-targeted drug delivery are discussed, with an emphasis on the relation between structural features and theranostic performance.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}