Pub Date : 2025-08-01Epub Date: 2025-04-22DOI: 10.1016/j.ajps.2025.101058
Zichao Yang , Jianwei Xu , Xixiang Yang , Jianjun Chen
Immunotherapy has transformed cancer treatment, marked by the approval of numerous antibody-based drugs. However, the limitations of antibodies in pharmacokinetics including long half-lives, limited oral bioavailability and immunogenicity, have prompted the pursuit of small molecule-based immunotherapy. Traditional drug discovery strategies, which focus on blocking protein activity through inhibitors, face persistent hurdles, such as reliance on accessible binding pockets, poor selectivity, and the emergence of drug resistance. Targeted protein degradation (TPD) technologies have emerged as powerful tools to address these limitations, offering significant therapeutic advantages over conventional inhibition strategies, particularly for historically ''undruggable'' targets. In recent years, small molecule-based protein degraders have rapidly advanced in cancer immunotherapy. In this review, we highlight recent progress in TPD-driven small-molecule drug discovery and summarize the application of these technologies in cancer immunotherapy, including degraders targeting PD-1/PD-L1, chemokine receptors, IDO1, AhR, and others.
{"title":"Targeted protein degradation with small molecules for cancer immunotherapy","authors":"Zichao Yang , Jianwei Xu , Xixiang Yang , Jianjun Chen","doi":"10.1016/j.ajps.2025.101058","DOIUrl":"10.1016/j.ajps.2025.101058","url":null,"abstract":"<div><div>Immunotherapy has transformed cancer treatment, marked by the approval of numerous antibody-based drugs. However, the limitations of antibodies in pharmacokinetics including long half-lives, limited oral bioavailability and immunogenicity, have prompted the pursuit of small molecule-based immunotherapy. Traditional drug discovery strategies, which focus on blocking protein activity through inhibitors, face persistent hurdles, such as reliance on accessible binding pockets, poor selectivity, and the emergence of drug resistance. Targeted protein degradation (TPD) technologies have emerged as powerful tools to address these limitations, offering significant therapeutic advantages over conventional inhibition strategies, particularly for historically ''undruggable'' targets. In recent years, small molecule-based protein degraders have rapidly advanced in cancer immunotherapy. In this review, we highlight recent progress in TPD-driven small-molecule drug discovery and summarize the application of these technologies in cancer immunotherapy, including degraders targeting PD-1/PD-L1, chemokine receptors, IDO1, AhR, and others.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101058"},"PeriodicalIF":11.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-05-24DOI: 10.1016/j.ajps.2025.101069
Zejun Xu , Jiaying Chi , Fei Qin , Dongyan Liu , Yecai Lai , Yingxia Bao , Ruizhi Guo , Yiqiu liao , Zhoufan Xie , Jieqiong Jiang , Juyan Liu , Jianfeng Cai , Chao Lu , Jiansong Wang , Chuanbin Wu
Nanoparticles-incorporated hydrogel microneedles (NPs-HMN) have attracted significant attention due to their exceptional biomedical applications. The arrayed needle tips of NPs-HMN effectively penetrate the skin or tissue, enabling minimally invasive and painless delivery of therapeutic molecules into the tissue microenvironment. This approach has shown significant improvements in bioavailability and patient compliance. Moreover, the functionalized hydrogel materials of NPs-HMN exhibit a three-dimensional network structure resembling the extracellular matrix, along with controllable drug release, exceptional swelling ability, hydrophilicity, and biocompatibility. These characteristics broaden the potential applications of HMN in therapeutic and biosensing contexts. In addition, the incorporation of nanoparticles (NPs) has been shown to improve the solubility of hydrophobic drugs, enhance mechanical properties, enable intelligent drug release, and facilitate precise targeting of HMN. The versatility and diversity of treatment options afforded by NPs-HMN contribute to significant advancements in animal models and clinical settings, as well as offer valuable insights for biomaterial development. This review provides a comprehensive examination of the fabrication strategies of NPs-HMN and their recent advancements in biomedical applications. We also analyze the mechanisms, advantages, challenges, and future prospects of this system in enhancing drug delivery efficiency to provide theoretical references for further breakthroughs in novel delivery platforms.
{"title":"Nanoparticles-incorporated hydrogel microneedle for biomedical applications: Fabrication strategies, emerging trends and future prospects","authors":"Zejun Xu , Jiaying Chi , Fei Qin , Dongyan Liu , Yecai Lai , Yingxia Bao , Ruizhi Guo , Yiqiu liao , Zhoufan Xie , Jieqiong Jiang , Juyan Liu , Jianfeng Cai , Chao Lu , Jiansong Wang , Chuanbin Wu","doi":"10.1016/j.ajps.2025.101069","DOIUrl":"10.1016/j.ajps.2025.101069","url":null,"abstract":"<div><div>Nanoparticles-incorporated hydrogel microneedles (NPs-HMN) have attracted significant attention due to their exceptional biomedical applications. The arrayed needle tips of NPs-HMN effectively penetrate the skin or tissue, enabling minimally invasive and painless delivery of therapeutic molecules into the tissue microenvironment. This approach has shown significant improvements in bioavailability and patient compliance. Moreover, the functionalized hydrogel materials of NPs-HMN exhibit a three-dimensional network structure resembling the extracellular matrix, along with controllable drug release, exceptional swelling ability, hydrophilicity, and biocompatibility. These characteristics broaden the potential applications of HMN in therapeutic and biosensing contexts. In addition, the incorporation of nanoparticles (NPs) has been shown to improve the solubility of hydrophobic drugs, enhance mechanical properties, enable intelligent drug release, and facilitate precise targeting of HMN. The versatility and diversity of treatment options afforded by NPs-HMN contribute to significant advancements in animal models and clinical settings, as well as offer valuable insights for biomaterial development. This review provides a comprehensive examination of the fabrication strategies of NPs-HMN and their recent advancements in biomedical applications. We also analyze the mechanisms, advantages, challenges, and future prospects of this system in enhancing drug delivery efficiency to provide theoretical references for further breakthroughs in novel delivery platforms.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101069"},"PeriodicalIF":11.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-03-30DOI: 10.1016/j.ajps.2025.101053
Liting Cheng , Zhongyi Ma , Xinlin Yang , Xue Wang , Yuqiong Wang , Xinlong Liu , Zhongjie Tang , Dingxi Jang , Guojian Liao , Tongbao Liu , Shuang Wu , Chong Li
Cryptococcosis, a serious systemic fungal infection caused by Cryptococcus neoformans (C. neoformans) and its variants, poses a significant clinical challenge due to its poor prognosis and severe health implications. The treatment of cryptococcal infections is complicated by several unique factors, stemming from both the pathogenic characteristics of the fungi and the biological barriers they exploit. These include the fungi's protective capsule, their ability to reside within host macrophages—thereby evading pharmacological intervention—and their involvement in multi-organ infections such as the lung and brain, in particular their strategic positioning within the brain, protected by the blood-brain barrier (BBB). To overcome these obstacles, precise active targeting emerges as a pivotal strategy. Identifying common targets is imperative to enhance therapeutic efficacy while ensuring the druggability of delivery systems. However, research on the methodology for selecting such shared targets remains sparse. In our investigation, we have pioneered the use of secreted proteins as shared target to trace the pathogens and their infection pathways. We identified the mannoprotein Cig1, prominently expressed on the surfaces of infected macrophages, lungs, and brains, as a viable shared target. On this basis, we utilized Hemin, a ligand for Cig1, to design liposomes (Hemin Lip) tailored for addressing complex fungal infections. By leveraging the interaction with the secreted protein Cig1, Hemin Lip specifically identifies and binds to organs and macrophages harboring cryptococcal infections, thereby facilitating targeted and efficacious clearance of both intracellular and extracellular fungus. Moreover, we have extended this targeting mechanism to other nanomedicinal platforms, including albumin nanoparticles. This study proposes an innovative drug delivery model that targets extracellular secretory proteins within the infection microenvironment, offering a streamlined formulation with the potential for effective therapy against complex infections.
{"title":"All-stage targeted therapy for invasive cryptococcosis through interaction between the secretory protein Cig1 and hemin","authors":"Liting Cheng , Zhongyi Ma , Xinlin Yang , Xue Wang , Yuqiong Wang , Xinlong Liu , Zhongjie Tang , Dingxi Jang , Guojian Liao , Tongbao Liu , Shuang Wu , Chong Li","doi":"10.1016/j.ajps.2025.101053","DOIUrl":"10.1016/j.ajps.2025.101053","url":null,"abstract":"<div><div>Cryptococcosis, a serious systemic fungal infection caused by <em>Cryptococcus neoformans</em> (<em>C. neoformans</em>) and its variants, poses a significant clinical challenge due to its poor prognosis and severe health implications. The treatment of cryptococcal infections is complicated by several unique factors, stemming from both the pathogenic characteristics of the fungi and the biological barriers they exploit. These include the fungi's protective capsule, their ability to reside within host macrophages—thereby evading pharmacological intervention—and their involvement in multi-organ infections such as the lung and brain, in particular their strategic positioning within the brain, protected by the blood-brain barrier (BBB). To overcome these obstacles, precise active targeting emerges as a pivotal strategy. Identifying common targets is imperative to enhance therapeutic efficacy while ensuring the druggability of delivery systems. However, research on the methodology for selecting such shared targets remains sparse. In our investigation, we have pioneered the use of secreted proteins as shared target to trace the pathogens and their infection pathways. We identified the mannoprotein Cig1, prominently expressed on the surfaces of infected macrophages, lungs, and brains, as a viable shared target. On this basis, we utilized Hemin, a ligand for Cig1, to design liposomes (Hemin Lip) tailored for addressing complex fungal infections. By leveraging the interaction with the secreted protein Cig1, Hemin Lip specifically identifies and binds to organs and macrophages harboring cryptococcal infections, thereby facilitating targeted and efficacious clearance of both intracellular and extracellular fungus. Moreover, we have extended this targeting mechanism to other nanomedicinal platforms, including albumin nanoparticles. This study proposes an innovative drug delivery model that targets extracellular secretory proteins within the infection microenvironment, offering a streamlined formulation with the potential for effective therapy against complex infections.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101053"},"PeriodicalIF":11.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-04-22DOI: 10.1016/j.ajps.2025.101061
Hee Won Park , Dae Hyun Lee , Sungjun Kim , Hyeri Park , Ashok Kumar Jangid , Chae Eun Lee , Jaewon Park , Gyu Tae Park , Ha Yeon Park , HyunJin Kim , Jae Ho Kim , Gi Jin Kim , Kyobum Kim
The global mortality rate due to liver diseases, particularly liver fibrosis, is increasing. Among various treatment methods, stem cell therapy using placenta-derived mesenchymal stem cells (PDMSCs) offers distinct benefits, including ease of isolation and superior proliferative potential. To enhance the therapeutic efficacy of PDMSCs, the WKYMVm peptide was selected for cell engineering. Immobilization of WKYMVm on PDMSC membranes facilitates effective peptide binding to the formyl peptide receptor 2 on adjacent PDMSCs and hepatocytes, thereby enhancing cell activation and achieving more efficient peptide utilization compared to bolus peptide treatment. Increased cell activation enhances the secretion of paracrine factors including growth factors and cytokines, which in turn improves liver function and vascular repair in both in vitro and in vivo models. This approach not only enhances the angiogenic and therapeutic capacities of stem cells, but also enables efficient peptide utilization, minimizing potential side effects and costs associated with high peptide dosages. Overall, our study demonstrates significant promise of stem cell therapy for treating liver fibrosis. Thus, stem cell therapy offers considerable prospects for clinical applications.
{"title":"Amphiphilic lipid-peptide engineered placenta-derived mesenchymal stem cells for liver fibrosis treatment","authors":"Hee Won Park , Dae Hyun Lee , Sungjun Kim , Hyeri Park , Ashok Kumar Jangid , Chae Eun Lee , Jaewon Park , Gyu Tae Park , Ha Yeon Park , HyunJin Kim , Jae Ho Kim , Gi Jin Kim , Kyobum Kim","doi":"10.1016/j.ajps.2025.101061","DOIUrl":"10.1016/j.ajps.2025.101061","url":null,"abstract":"<div><div>The global mortality rate due to liver diseases, particularly liver fibrosis, is increasing. Among various treatment methods, stem cell therapy using placenta-derived mesenchymal stem cells (PDMSCs) offers distinct benefits, including ease of isolation and superior proliferative potential. To enhance the therapeutic efficacy of PDMSCs, the WKYMVm peptide was selected for cell engineering. Immobilization of WKYMVm on PDMSC membranes facilitates effective peptide binding to the formyl peptide receptor 2 on adjacent PDMSCs and hepatocytes, thereby enhancing cell activation and achieving more efficient peptide utilization compared to bolus peptide treatment. Increased cell activation enhances the secretion of paracrine factors including growth factors and cytokines, which in turn improves liver function and vascular repair in both <em>in vitro</em> and <em>in vivo</em> models. This approach not only enhances the angiogenic and therapeutic capacities of stem cells, but also enables efficient peptide utilization, minimizing potential side effects and costs associated with high peptide dosages. Overall, our study demonstrates significant promise of stem cell therapy for treating liver fibrosis. Thus, stem cell therapy offers considerable prospects for clinical applications.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101061"},"PeriodicalIF":10.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-02-12DOI: 10.1016/j.ajps.2025.101035
Huijuan Zhang , Zijun Qi , Chaoqun Wang , Yingmei Tian , Lin Hou
To develop an efficient thrombolytic therapy approach that addresses the limitations of current fibrinolytic drugs, such as short half-life, weak thrombus specificity and poor penetration ability, we constructed a NIR-triggered detachable nanoplatform (PA/UK@IcpLipo) using thin-film hydration method. It was designed to integrate attack and defense mechanisms for thrombolytic therapy. This platform can actively identify thrombi by binding to GPIIb-IIIa receptors overexpressed on activated platelets. Upon NIR laser activation and interaction with thrombin in the thrombotic microenvironment, the thermosensitive liposomes rupture, releasing the PA/UK core for deep penetration into the thrombus. Our results showed that the PA/UK@IcpLipo nanoplatform efficiently promoted rapid thrombolysis under the action of UK (attack), followed by PA exerting an antiplatelet aggregation effect (defense). This dual-action approach significantly improved vascular reperfusion rates. The NIR-triggered detachable nanoplatform offered a promising solution for enhanced thrombolysis efficiency and reduced bleeding risk, addressing critical limitations of current fibrinolytic therapies.
{"title":"Dual-responsive and NIR-triggered detachable nanoplatform for integrated thrombolytic and antiplatelet therapy","authors":"Huijuan Zhang , Zijun Qi , Chaoqun Wang , Yingmei Tian , Lin Hou","doi":"10.1016/j.ajps.2025.101035","DOIUrl":"10.1016/j.ajps.2025.101035","url":null,"abstract":"<div><div>To develop an efficient thrombolytic therapy approach that addresses the limitations of current fibrinolytic drugs, such as short half-life, weak thrombus specificity and poor penetration ability, we constructed a NIR-triggered detachable nanoplatform (PA/UK@IcpLipo) using thin-film hydration method. It was designed to integrate attack and defense mechanisms for thrombolytic therapy. This platform can actively identify thrombi by binding to GPIIb-IIIa receptors overexpressed on activated platelets. Upon NIR laser activation and interaction with thrombin in the thrombotic microenvironment, the thermosensitive liposomes rupture, releasing the PA/UK core for deep penetration into the thrombus. Our results showed that the PA/UK@IcpLipo nanoplatform efficiently promoted rapid thrombolysis under the action of UK (attack), followed by PA exerting an antiplatelet aggregation effect (defense). This dual-action approach significantly improved vascular reperfusion rates. The NIR-triggered detachable nanoplatform offered a promising solution for enhanced thrombolysis efficiency and reduced bleeding risk, addressing critical limitations of current fibrinolytic therapies.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101035"},"PeriodicalIF":11.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-05-27DOI: 10.1016/j.ajps.2025.101070
Ruijie Qian , Yawen Guo , Xuemei Gao , Jianzhuang Ren , Dawei Jiang , Rui An , Ruihua Wang , Xuhua Duan , Xinwei Han
Cerenkov radiation (CR) can serve as a source of internal light to overcome the limited tissue penetration of external light in conventional photodynamic therapy (PDT). However, insufficient luminescence intensity hinders the clinical application of CR-PDT. Here, we developed a glutathione-responsive biomimetic nanoplatform by fusing cancer cell membranes and liposomes loaded with photosensitizer hematoporphyrin monomethyl ether (HMME) and a radiation energy amplifier Eu3+, named HMME-Eu@LEV. Colloidal Eu3+ converts γ-radiation and CR from radioisotopes into fluorescence to enhance anti-tumor effects. Sequential administration ensures co-localization of HMME-Eu@LEV and radiopharmaceutical 18F-fluorodeoxyglucose (FDG) at the tumor site, triggering enhanced CR-PDT and immunogenic cell death. Our observations indicated that luminescence resonance energy transfer between Eu3+ and HMME was efficient, and Cerenkov luminescence from Eu@LEV+FDG was approximately 5.6-fold higher in intensity than that from FDG alone. As a result, abundant ROS were generated, and macrophages in the tumor microenvironment were polarized from M2 to M1. In addition, the immunosuppressive tumor microenvironment could be reversed by promoting the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes. The activated immune system effectively inhibited the growth of primary tumors and spread of distant metastases. Our work demonstrates the feasibility of CR-PDT without an external light source and the critical role of nanomaterials in personalized medicine.
{"title":"Enhanced Cerenkov radiation induced photodynamic therapy based on GSH-responsive biomimetic nanoplatform to trigger immunogenic cell death for tumor immunotherapy","authors":"Ruijie Qian , Yawen Guo , Xuemei Gao , Jianzhuang Ren , Dawei Jiang , Rui An , Ruihua Wang , Xuhua Duan , Xinwei Han","doi":"10.1016/j.ajps.2025.101070","DOIUrl":"10.1016/j.ajps.2025.101070","url":null,"abstract":"<div><div>Cerenkov radiation (CR) can serve as a source of internal light to overcome the limited tissue penetration of external light in conventional photodynamic therapy (PDT). However, insufficient luminescence intensity hinders the clinical application of CR-PDT. Here, we developed a glutathione-responsive biomimetic nanoplatform by fusing cancer cell membranes and liposomes loaded with photosensitizer hematoporphyrin monomethyl ether (HMME) and a radiation energy amplifier Eu<sup>3+</sup>, named HMME-Eu@LEV. Colloidal Eu<sup>3+</sup> converts γ-radiation and CR from radioisotopes into fluorescence to enhance anti-tumor effects. Sequential administration ensures co-localization of HMME-Eu@LEV and radiopharmaceutical <sup>18</sup>F-fluorodeoxyglucose (FDG) at the tumor site, triggering enhanced CR-PDT and immunogenic cell death. Our observations indicated that luminescence resonance energy transfer between Eu<sup>3+</sup> and HMME was efficient, and Cerenkov luminescence from Eu@LEV+FDG was approximately 5.6-fold higher in intensity than that from FDG alone. As a result, abundant ROS were generated, and macrophages in the tumor microenvironment were polarized from M2 to M1. In addition, the immunosuppressive tumor microenvironment could be reversed by promoting the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes. The activated immune system effectively inhibited the growth of primary tumors and spread of distant metastases. Our work demonstrates the feasibility of CR-PDT without an external light source and the critical role of nanomaterials in personalized medicine.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101070"},"PeriodicalIF":10.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-01-31DOI: 10.1016/j.ajps.2025.101023
Zhiyuan Tang , Yuening Sun , Quanhua Yi , Qian Ding , Yang Ding , Jianfei Huang
The effective intracellular accumulation of doxorubicin (DOX) is crucial for improving antitumor efficacy, which is severely impeded by limited drug penetration, uncontrollable drug release, and drug resistance. In this study, a thermal-deformative polymer embedding ultrasmall ceria (CeO2) was rationally designed for deep tumor drug shuttling and hypoxia reversal to improve chemotherapy. Structurally, the CeO2 nanozyme was covalently grafted with a polymer of p(NIPAM-co-AM) that could sharply shrink for DOX loading, which was consolidated with polydopamine (PDA) film encapsulation. Thereafter, a tumor penetration guide of apolipoprotein A-I (apoA-I) conjugated iRGD peptide (apoA-I-iRGD) was further decorated onto the PDA shell via Michael addition for preparing CeO2P/DOX@iAPDA. With the aid of apoA-I-iRGD, CeO2P/DOX@iAPDA penetrated both the tumor spheroids (∼78 µm) and the tumors of the mouse model deeply. After internalization by tumor cells and triggering by low pH in lysosomes, rapid DOX release was achieved by peeling off the PDA shell and thermosensitive deformation of p(NIPAM-co-AM). CeO2P/DOX@iAPDA provided 66.4 % tumor suppression in 4T1-derived tumor spheroids and 63.2 % in 4T1-tumor-bearing mice, respectively. Preliminary mechanistic research involving western blotting and immunohistochemistry revealed that CeO2P/DOX@iAPDA reversed resistance through the through HIF-1α-P-gp/lipid axis. Collectively, this study intelligently integrated CeO2 nanozymes, temperature-sensitive polymers, and imitated biochemical modifications to improve chemotherapy for breast cancer.
{"title":"CeO2 nanozyme-embedded thermal-deformative polymer for site-specific chemotherapy via HIF-1α-P-gp/lipolysis axis reversal","authors":"Zhiyuan Tang , Yuening Sun , Quanhua Yi , Qian Ding , Yang Ding , Jianfei Huang","doi":"10.1016/j.ajps.2025.101023","DOIUrl":"10.1016/j.ajps.2025.101023","url":null,"abstract":"<div><div>The effective intracellular accumulation of doxorubicin (DOX) is crucial for improving antitumor efficacy, which is severely impeded by limited drug penetration, uncontrollable drug release, and drug resistance. In this study, a thermal-deformative polymer embedding ultrasmall ceria (CeO<sub>2</sub>) was rationally designed for deep tumor drug shuttling and hypoxia reversal to improve chemotherapy. Structurally, the CeO<sub>2</sub> nanozyme was covalently grafted with a polymer of p(NIPAM-co-AM) that could sharply shrink for DOX loading, which was consolidated with polydopamine (PDA) film encapsulation. Thereafter, a tumor penetration guide of apolipoprotein A-I (apoA-I) conjugated iRGD peptide (apoA-I-iRGD) was further decorated onto the PDA shell via Michael addition for preparing CeO<sub>2</sub>P/DOX@iAPDA. With the aid of apoA-I-iRGD, CeO<sub>2</sub>P/DOX@iAPDA penetrated both the tumor spheroids (∼78 µm) and the tumors of the mouse model deeply. After internalization by tumor cells and triggering by low pH in lysosomes, rapid DOX release was achieved by peeling off the PDA shell and thermosensitive deformation of p(NIPAM-co-AM). CeO<sub>2</sub>P/DOX@iAPDA provided 66.4 % tumor suppression in 4T1-derived tumor spheroids and 63.2 % in 4T1-tumor-bearing mice, respectively. Preliminary mechanistic research involving western blotting and immunohistochemistry revealed that CeO<sub>2</sub>P/DOX@iAPDA reversed resistance through the through HIF-1α-P-gp/lipid axis. Collectively, this study intelligently integrated CeO<sub>2</sub> nanozymes, temperature-sensitive polymers, and imitated biochemical modifications to improve chemotherapy for breast cancer.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 3","pages":"Article 101023"},"PeriodicalIF":10.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-03-14DOI: 10.1016/j.ajps.2025.101043
Jun Quan Ng , Nabil Ajwad Abu Yazid , Shing Cheng Tan , Mastura Monif , Tin Wui Wong , Si-Yuen Lee
Current treatments for glioblastoma face challenges such as the blood-brain barrier and lack of targeted therapy, compounded by the aggressive nature, high invasiveness, and heterogeneity of the disease. Exosomes, a subtype of extracellular vesicles are emerging as promising nanocarrier drug delivery systems to address these limitations. Exosomes released by all cell types can be easily obtained and modified as delivery vehicles or therapeutic agents. A systematic review was conducted to evaluate various methods for exosome isolation, characterization, engineering or modification, drug loading and delivery efficiency, including exosome biodistribution and treatment efficacy. A search of four databases for in vitro and in vivo studies (2000–,2023) identified 6165 records, of which 23 articles were found eligible and included for analyses. Most studies applied ultracentrifugation (UC) for exosomes isolation. Cancer cell lines being the most frequently used source of exosomes, followed by stem cells. The incubation approach was predominantly utilized to modify exosomes for drug loading. In vivo analysis showed that exosome biodistribution was primarily concentrated in the brain region, peaking in the first 6 h and remained moderately high. Compared to native exosomes and untreated control groups, utilizing modified native exosomes (cargo loaded) for treating glioblastoma disease models led to more pronounced suppression of tumor growth and proliferation, enhanced stimulation of immune response and apoptosis, effective restoration of drug chemosensitivity, increased anti-tumor effect and prolonged survival rates. Modified exosomes whether through incubation, sonication, transfection, freeze-thawing or their combination, improve targeted delivery and therapeutic efficacy against glioblastoma.
{"title":"Extracellular vesicles as delivery vehicles and therapeutic agents for glioblastoma treatment: A systematic review of in vitro and in vivo preclinical studies","authors":"Jun Quan Ng , Nabil Ajwad Abu Yazid , Shing Cheng Tan , Mastura Monif , Tin Wui Wong , Si-Yuen Lee","doi":"10.1016/j.ajps.2025.101043","DOIUrl":"10.1016/j.ajps.2025.101043","url":null,"abstract":"<div><div>Current treatments for glioblastoma face challenges such as the blood-brain barrier and lack of targeted therapy, compounded by the aggressive nature, high invasiveness, and heterogeneity of the disease. Exosomes, a subtype of extracellular vesicles are emerging as promising nanocarrier drug delivery systems to address these limitations. Exosomes released by all cell types can be easily obtained and modified as delivery vehicles or therapeutic agents. A systematic review was conducted to evaluate various methods for exosome isolation, characterization, engineering or modification, drug loading and delivery efficiency, including exosome biodistribution and treatment efficacy. A search of four databases for <em>in vitro</em> and <em>in vivo</em> studies (2000–,2023) identified 6165 records, of which 23 articles were found eligible and included for analyses. Most studies applied ultracentrifugation (UC) for exosomes isolation. Cancer cell lines being the most frequently used source of exosomes, followed by stem cells. The incubation approach was predominantly utilized to modify exosomes for drug loading. In vivo analysis showed that exosome biodistribution was primarily concentrated in the brain region, peaking in the first 6 h and remained moderately high. Compared to native exosomes and untreated control groups, utilizing modified native exosomes (cargo loaded) for treating glioblastoma disease models led to more pronounced suppression of tumor growth and proliferation, enhanced stimulation of immune response and apoptosis, effective restoration of drug chemosensitivity, increased anti-tumor effect and prolonged survival rates. Modified exosomes whether through incubation, sonication, transfection, freeze-thawing or their combination, improve targeted delivery and therapeutic efficacy against glioblastoma.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 3","pages":"Article 101043"},"PeriodicalIF":10.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mimicking the hierarchical structure of the skin is one of the most important strategies in skin tissue engineering. Monolayer wound dressings are usually not able to provide several functions at the same time and cannot meet all clinical needs. In order to maximize therapeutic efficiency, herein, we fabricated a Tri-layer wound dressing, where the middle layer was fabricated via 3D-printing and composed of alginate, tragacanth and zinc oxide nanoparticles (ZnO NPs). Both upper and bottom layers were constructed using electrospinning technique; the upper layer was made of hydrophobic polycaprolactone to mimic epidermis, while the bottom layer consisted of Soluplus® and insulin-like growth factor-1 (IGF-1) to promote cell behavior. Swelling, water vapor permeability and tensile properties of the dressings were evaluated and the Tri-layer dressing exhibited impressive antibacterial activity and cell stimulation following by the release of ZnO NPs and IGF-1. Additionally, the Tri-layer dressing led to faster healing of full-thickness wound in rat model compared to monolayer and Bilayer dressings. Overall, the evidence confirmed that the Tri-layer wound dressing is extremely effective for full-thickness wound healing.
{"title":"Multifunctional tri-layer wound dressing containing ZNO nanoparticles and IGF-1 as an efficient biomaterial for healing of full thickness skin injuries","authors":"Azin Abedi Koupai , Jaleh Varshosaz , Mohamadreza Tavakoli , Marjan Mirhaj , Saeideh Salehi , Faramarz Dobakhti","doi":"10.1016/j.ajps.2025.101039","DOIUrl":"10.1016/j.ajps.2025.101039","url":null,"abstract":"<div><div>Mimicking the hierarchical structure of the skin is one of the most important strategies in skin tissue engineering. Monolayer wound dressings are usually not able to provide several functions at the same time and cannot meet all clinical needs. In order to maximize therapeutic efficiency, herein, we fabricated a Tri-layer wound dressing, where the middle layer was fabricated via 3D-printing and composed of alginate, tragacanth and zinc oxide nanoparticles (ZnO NPs). Both upper and bottom layers were constructed using electrospinning technique; the upper layer was made of hydrophobic polycaprolactone to mimic epidermis, while the bottom layer consisted of Soluplus® and insulin-like growth factor-1 (IGF-1) to promote cell behavior. Swelling, water vapor permeability and tensile properties of the dressings were evaluated and the Tri-layer dressing exhibited impressive antibacterial activity and cell stimulation following by the release of ZnO NPs and IGF-1. Additionally, the Tri-layer dressing led to faster healing of full-thickness wound in rat model compared to monolayer and Bilayer dressings. Overall, the evidence confirmed that the Tri-layer wound dressing is extremely effective for full-thickness wound healing.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 3","pages":"Article 101039"},"PeriodicalIF":10.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144072737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Microneedle-mediated drug delivery systems (MDDS) have experienced robust growth in recent years, with designers leveraging their creativity to apply these systems for direct drug delivery to the skin, mucous membranes, blood vessel walls and even internal organs. In order to achieve precise drug delivery, various delicately conceived drug release modes based on MDDS have been developed. Herein, to elucidate the design concepts of numerous reported MDDS, we have categorized them into two levels (Level-Ⅰ MDDS and Level-Ⅱ MDDS) depending on whether nanoscale and microscale carriers are integrated within the microneedles. In this work, the design strategies of MDDS, as well as the current status of their applications in targeted and intelligent drug delivery were reviewed, while their prospects and challenges for future industrialization and clinical applications were also discussed.
{"title":"Progressive microneedles for targeting and intelligent drug delivery","authors":"Jiaqi Li, Qing Xia, Shuwen Ma, Zhi Wang, Teng Guo, Nianping Feng, Yongtai Zhang","doi":"10.1016/j.ajps.2025.101051","DOIUrl":"10.1016/j.ajps.2025.101051","url":null,"abstract":"<div><div>Microneedle-mediated drug delivery systems (MDDS) have experienced robust growth in recent years, with designers leveraging their creativity to apply these systems for direct drug delivery to the skin, mucous membranes, blood vessel walls and even internal organs. In order to achieve precise drug delivery, various delicately conceived drug release modes based on MDDS have been developed. Herein, to elucidate the design concepts of numerous reported MDDS, we have categorized them into two levels (Level-Ⅰ MDDS and Level-Ⅱ MDDS) depending on whether nanoscale and microscale carriers are integrated within the microneedles. In this work, the design strategies of MDDS, as well as the current status of their applications in targeted and intelligent drug delivery were reviewed, while their prospects and challenges for future industrialization and clinical applications were also discussed.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 3","pages":"Article 101051"},"PeriodicalIF":10.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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