Pub Date : 2025-02-01DOI: 10.1016/j.ajps.2024.100990
Mengying Cheng , Tianxiang Yue , Hong Wang , Lai Jiang , Qiaoling Huang , Fanzhu Li
Atherosclerosis (AS) is a progressive inflammatory disease, and thrombosis most likely leads to cardiovascular morbidity and mortality globally. Thrombolytic drugs alone cannot completely prevent thrombotic events, and treatments targeting thrombosis also need to regulate the inflammatory process. Based on the dynamic pathological development of AS, biomimetic thrombus-targeted nanoparticles HMTL@PM were prepared. Hirudin and lumbrukinase, effective substances of traditional Chinese medicine, were self-assembled under the action of tannic acid and Mn2+. HMTL@PM dissociated in the weakly acidic microenvironment of atherosclerosis and exhibited excellent therapeutic effects, including alleviating inflammation, dissolving thrombus, anticoagulation, and promoting cholesterol efflux. HMTL@PM effectively regulated the progression of AS and provided a new perspective for the development of drug delivery systems for AS therapy, which holds important research significance for reducing the mortality of cardiovascular and cerebrovascular diseases.
{"title":"Biomimetic nanoparticles co-deliver hirudin and lumbrukinase to ameliorate thrombus and inflammation for atherosclerosis therapy","authors":"Mengying Cheng , Tianxiang Yue , Hong Wang , Lai Jiang , Qiaoling Huang , Fanzhu Li","doi":"10.1016/j.ajps.2024.100990","DOIUrl":"10.1016/j.ajps.2024.100990","url":null,"abstract":"<div><div>Atherosclerosis (AS) is a progressive inflammatory disease, and thrombosis most likely leads to cardiovascular morbidity and mortality globally. Thrombolytic drugs alone cannot completely prevent thrombotic events, and treatments targeting thrombosis also need to regulate the inflammatory process. Based on the dynamic pathological development of AS, biomimetic thrombus-targeted nanoparticles HMTL@PM were prepared. Hirudin and lumbrukinase, effective substances of traditional Chinese medicine, were self-assembled under the action of tannic acid and Mn<sup>2+</sup>. HMTL@PM dissociated in the weakly acidic microenvironment of atherosclerosis and exhibited excellent therapeutic effects, including alleviating inflammation, dissolving thrombus, anticoagulation, and promoting cholesterol efflux. HMTL@PM effectively regulated the progression of AS and provided a new perspective for the development of drug delivery systems for AS therapy, which holds important research significance for reducing the mortality of cardiovascular and cerebrovascular diseases.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 100990"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143102276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ajps.2024.100993
Fugen Wu , Xingsi An , Shize Li , Chenyu Qiu , Yixuan Zhu , Zhanzheng Ye , Shengnan Song , Yunzhi Wang , Dingchao Shen , Xinyu Di , Yinsha Yao , Wanling Zhu , Xinyu Jiang , Xianbao Shi , Ruijie Chen , Longfa Kou
Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death (ICD), making it a promising strategy for clinical application. Alantolactone (A) was found to augment the anticancer efficacy of paclitaxel (P) at a molar ratio of 1:0.5 (P:A) through induction of more potent ICD via modulation of STAT3 signaling pathways. Nano drug delivery systems can synergistically combine natural drugs with conventional chemotherapeutic agents, thereby enhancing multi-drug chemoimmunotherapy. To improve tumor targeting ability and bioavailability of hydrophobic drugs, an amphiphilic prodrug conjugate (HA-PTX) was chemically modified with paclitaxel (PTX) and hyaluronic acid (HA) as a backbone. Based on this concept, CD44-targeted nanodrugs (A@HAP NPs) were developed for co-delivery of A and P in colorectal cancer treatment, aiming to achieve synergistic toxicity-based chemo-immunotherapy. The uniform size and high drug loading capacity of A@HAP NPs facilitated their accumulation within tumors through enhanced permeability and retention effect as well as HA-mediated targeting, providing a solid foundation for subsequent synergistic therapy and immunoregulation. In vitro and in vivo studies demonstrated that A@HAP NPs exhibited potent cytotoxicity against tumor cells while also remodeling the immune-suppressive tumor microenvironment by promoting antigen presentation and inducing dendritic cell maturation, thus offering a novel approach for colorectal cancer chemoimmunotherapy.
{"title":"Enhancing chemoimmunotherapy for colorectal cancer with paclitaxel and alantolactone via CD44-Targeted nanoparticles: A STAT3 signaling pathway modulation approach","authors":"Fugen Wu , Xingsi An , Shize Li , Chenyu Qiu , Yixuan Zhu , Zhanzheng Ye , Shengnan Song , Yunzhi Wang , Dingchao Shen , Xinyu Di , Yinsha Yao , Wanling Zhu , Xinyu Jiang , Xianbao Shi , Ruijie Chen , Longfa Kou","doi":"10.1016/j.ajps.2024.100993","DOIUrl":"10.1016/j.ajps.2024.100993","url":null,"abstract":"<div><div>Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death (ICD), making it a promising strategy for clinical application. Alantolactone (A) was found to augment the anticancer efficacy of paclitaxel (P) at a molar ratio of 1:0.5 (P:A) through induction of more potent ICD via modulation of STAT3 signaling pathways. Nano drug delivery systems can synergistically combine natural drugs with conventional chemotherapeutic agents, thereby enhancing multi-drug chemoimmunotherapy. To improve tumor targeting ability and bioavailability of hydrophobic drugs, an amphiphilic prodrug conjugate (HA-PTX) was chemically modified with paclitaxel (PTX) and hyaluronic acid (HA) as a backbone. Based on this concept, CD44-targeted nanodrugs (A@HAP NPs) were developed for co-delivery of A and P in colorectal cancer treatment, aiming to achieve synergistic toxicity-based chemo-immunotherapy. The uniform size and high drug loading capacity of A@HAP NPs facilitated their accumulation within tumors through enhanced permeability and retention effect as well as HA-mediated targeting, providing a solid foundation for subsequent synergistic therapy and immunoregulation. <em>In vitro</em> and <em>in vivo</em> studies demonstrated that A@HAP NPs exhibited potent cytotoxicity against tumor cells while also remodeling the immune-suppressive tumor microenvironment by promoting antigen presentation and inducing dendritic cell maturation, thus offering a novel approach for colorectal cancer chemoimmunotherapy.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 100993"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143102275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arthritis is an inflammatory joint disorder that progressively impairs function and diminishes quality of life. Conventional therapies often prove ineffective, as oral administration lacks specificity, resulting in off-target side effects like hepatotoxicity and GIT-related issues. Intravenous administration causes systemic side effects. The characteristic joint-localized symptoms such as pain, stiffness, and inflammation make the localized drug delivery suitable for managing arthritis. Topical/transdermal/intra-articular routes have become viable options for drug delivery in treating arthritis. However, challenges with those localized drug delivery routes include skin barrier and cartilage impermeability. Additionally, conventional intra-articular drug delivery also leads to rapid clearance of drugs from the synovial joint tissue. To circumvent these limitations, researchers have developed nanocarriers that enhance drug permeability through skin and cartilage, influencing localized action. Gel-based nanoengineered therapy employs a gel matrix to incorporate the drug-encapsulated nanocarriers. This approach combines the benefits of gels and nanocarriers to enhance therapeutic effects and improve patient compliance. This review emphasizes deep insights into drug delivery using diverse gel-based novel nanocarriers, exploring their various applications embedded in hyaluronic acid (biopolymer)–based gels, carbopol-based gels, and others. Furthermore, this review discusses the influence of nanocarrier pharmacokinetics on the localization and therapeutic manipulation of macrophages mediated by nanocarriers. The ELVIS (extravasation through leaky vasculature and inflammatory cell-mediated sequestration) effect associated with arthritis is advantageous in drug delivery. Simply put, the ELVIS effect refers to the extravasation of nanocarriers through leaky vasculatures, which finally results in the accumulation of nanocarriers in the joint cavity.
{"title":"Deep-insights: Nanoengineered gel-based localized drug delivery for arthritis management","authors":"Anitha Sriram , Harshada Ithape , Pankaj Kumar Singh","doi":"10.1016/j.ajps.2024.101012","DOIUrl":"10.1016/j.ajps.2024.101012","url":null,"abstract":"<div><div>Arthritis is an inflammatory joint disorder that progressively impairs function and diminishes quality of life. Conventional therapies often prove ineffective, as oral administration lacks specificity, resulting in off-target side effects like hepatotoxicity and GIT-related issues. Intravenous administration causes systemic side effects. The characteristic joint-localized symptoms such as pain, stiffness, and inflammation make the localized drug delivery suitable for managing arthritis. Topical/transdermal/intra-articular routes have become viable options for drug delivery in treating arthritis. However, challenges with those localized drug delivery routes include skin barrier and cartilage impermeability. Additionally, conventional intra-articular drug delivery also leads to rapid clearance of drugs from the synovial joint tissue. To circumvent these limitations, researchers have developed nanocarriers that enhance drug permeability through skin and cartilage, influencing localized action. Gel-based nanoengineered therapy employs a gel matrix to incorporate the drug-encapsulated nanocarriers. This approach combines the benefits of gels and nanocarriers to enhance therapeutic effects and improve patient compliance. This review emphasizes deep insights into drug delivery using diverse gel-based novel nanocarriers, exploring their various applications embedded in hyaluronic acid (biopolymer)–based gels, carbopol-based gels, and others. Furthermore, this review discusses the influence of nanocarrier pharmacokinetics on the localization and therapeutic manipulation of macrophages mediated by nanocarriers. The ELVIS (extravasation through leaky vasculature and inflammatory cell-mediated sequestration) effect associated with arthritis is advantageous in drug delivery. Simply put, the ELVIS effect refers to the extravasation of nanocarriers through leaky vasculatures, which finally results in the accumulation of nanocarriers in the joint cavity.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 101012"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143336437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the current transformative era of biomedicine, hydrogels have established their presence in biomaterials due to their superior biocompatibility, tuneability and resemblance with native tissue. However, hydrogels typically exhibit poor conductivity due to their hydrophilic polymer structure. Electrical conductivity provides an important enhancement to the properties of hydrogel-based systems in various biomedical applications such as drug delivery and tissue engineering. Consequently, researchers are developing combinatorial strategies to develop electrically responsive “SMART” systems to improve the therapeutic efficacy of biomolecules. Electrically conductive hydrogels have been explored for various drug delivery applications, enabling higher loading of therapeutic cargo with on-demand delivery. This review emphasizes the properties, mechanisms, fabrication techniques and recent advancements of electrically responsive “SMART” systems aiding on-site drug delivery applications. Additionally, it covers prospects for the successful translation of these systems into clinical research.
{"title":"Electrically conductive “SMART” hydrogels for on-demand drug delivery","authors":"Soumajyoti Ghosh , Nikhil Kumar , Santanu Chattopadhyay","doi":"10.1016/j.ajps.2024.101007","DOIUrl":"10.1016/j.ajps.2024.101007","url":null,"abstract":"<div><div>In the current transformative era of biomedicine, hydrogels have established their presence in biomaterials due to their superior biocompatibility, tuneability and resemblance with native tissue. However, hydrogels typically exhibit poor conductivity due to their hydrophilic polymer structure. Electrical conductivity provides an important enhancement to the properties of hydrogel-based systems in various biomedical applications such as drug delivery and tissue engineering. Consequently, researchers are developing combinatorial strategies to develop electrically responsive “SMART” systems to improve the therapeutic efficacy of biomolecules. Electrically conductive hydrogels have been explored for various drug delivery applications, enabling higher loading of therapeutic cargo with on-demand delivery. This review emphasizes the properties, mechanisms, fabrication techniques and recent advancements of electrically responsive “SMART” systems aiding on-site drug delivery applications. Additionally, it covers prospects for the successful translation of these systems into clinical research.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 1","pages":"Article 101007"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143102268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub 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":"2025-01-31","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}
Temozolomide (TMZ) is considered as a standard-of-care DNA alkylating agent for treating glioblastoma multiforme. Despite being a highly potent molecule, TMZ poses several limitations, including short half-life, rapid metabolism, low brain bioavailability and dose-dependent toxicities. Attempts have been made to improve the delivery of TMZ that mainly exhibited nominal therapeutic outcomes. In the current study, we have conjugated TMZ to mPEG-b-P(CB-{g-COOH}) copolymer to obtain mPEG-b-P(CB-{g-COOH; g-TMZn}) that demonstrated improvement in stability and efficacy. Further, a hybrid TMZ nanoconjugate formulation was developed using mPEG-b-P(CB-{g-COOH; g-TMZ40}) and mPEG-polylactic acid (mPEG-PLA) showed an average size of 105.7 nm with narrow PDI of <0.2 and TMZ loading of 21.6 %. Stability was assessed under physiological conditions wherein TMZ was found to be stable with a half-life of ∼194 h compared to 1.8 h for free TMZ. The Hybrid TMZ nanoconjugates showed improved intracellular uptake and reduced IC50 values in C6 and U87MG glioma cells. Furthermore, they exhibited better in vivo therapeutic outcome, i.e., reduced brain weight, hemispherical width ratio and improved survival rate in C6-cell induced orthotropic glioma model in Sprague Dawley rats compared to the free TMZ-treated and positive control animals. Histopathological evaluation also revealed reduced cell infiltration in the lungs and reduced toxicity in major organs. Overall, the hybrid nanoconjugates of TMZ significantly improved its stability and efficacy in the GBM model, thereby opening newer avenues for treatment.
{"title":"Enhancing temozolomide in vivo stability and efficacy through hybrid nanoconjugate approach for improved glioblastoma multiforme treatment","authors":"Prabhjeet Singh , Deepak Kumar Sahel , Reena Jatyan , Kiran Bajaj , Anupama Mittal , Deepak Chitkara","doi":"10.1016/j.ajps.2025.101022","DOIUrl":"10.1016/j.ajps.2025.101022","url":null,"abstract":"<div><div>Temozolomide (TMZ) is considered as a standard-of-care DNA alkylating agent for treating glioblastoma multiforme. Despite being a highly potent molecule, TMZ poses several limitations, including short half-life, rapid metabolism, low brain bioavailability and dose-dependent toxicities. Attempts have been made to improve the delivery of TMZ that mainly exhibited nominal therapeutic outcomes. In the current study, we have conjugated TMZ to mPEG-b-P(CB-{g-COOH}) copolymer to obtain mPEG-b-P(CB-{g-COOH; g-TMZ<sub>n</sub>}) that demonstrated improvement in stability and efficacy. Further, a hybrid TMZ nanoconjugate formulation was developed using mPEG-b-P(CB-{g-COOH; g-TMZ<sub>40</sub>}) and mPEG-polylactic acid (mPEG-PLA) showed an average size of 105.7 nm with narrow PDI of <0.2 and TMZ loading of 21.6 %. Stability was assessed under physiological conditions wherein TMZ was found to be stable with a half-life of ∼194 h compared to 1.8 h for free TMZ. The Hybrid TMZ nanoconjugates showed improved intracellular uptake and reduced IC<sub>50</sub> values in C6 and U87MG glioma cells. Furthermore, they exhibited better <em>in vivo</em> therapeutic outcome, <em>i.e.</em>, reduced brain weight, hemispherical width ratio and improved survival rate in C6-cell induced orthotropic glioma model in <em>Sprague Dawley</em> rats compared to the free TMZ-treated and positive control animals. Histopathological evaluation also revealed reduced cell infiltration in the lungs and reduced toxicity in major organs. Overall, the hybrid nanoconjugates of TMZ significantly improved its stability and efficacy in the GBM model, thereby opening newer avenues for treatment.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 3","pages":"Article 101022"},"PeriodicalIF":10.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083915","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 : 2025-01-17DOI: 10.1016/j.ajps.2025.101021
Puja Sandhbor , Geofrey John , Sakshi Bhat , Jayant S. Goda
Although with aggressive standards of care like surgical resection, chemotherapy, and radiation, high-grade gliomas (HGGs) and brain metastases (BM) treatment has remained challenging for more than two decades. However, technological advances in this field and immunotherapeutic strategies have revolutionized the treatment of HGGs and BM. Immunotherapies like immune checkpoint inhibitors, CAR-T targeting, oncolytic virus-based therapy, bispecific antibody treatment, and vaccination approaches, etc., are emerging as promising avenues offering new hope in refining patient's survival benefits. However, selective trafficking across the blood-brain barrier (BBB), immunosuppressive tumor microenvironment (TME), metabolic alteration, and tumor heterogeneity limit the therapeutic efficacy of immunotherapy for HGGs and BM. Furthermore, to address this concern, the NanoBioTechnology-based bioinspired delivery system has been gaining tremendous attention in recent years. With technological advances such as Trojan horse targeting and infusing/camouflaging nanoparticles surface with biological molecules/cells like immunocytes, erythrocytes, platelets, glioma cell lysate and/or integrating these strategies to get hybrid membrane for homotypic recognition. These biomimetic nanotherapy offers advantages over conventional nanoparticles, focusing on greater target specificity, increased circulation stability, higher active loading capacity, BBB permeability (inherent inflammatory chemotaxis of neutrophils), decreased immunogenicity, efficient metabolism-based combinatorial effects, and prevention of tumor recurrence by induction of immunological memory, etc. provide new age of improved immunotherapies outcomes against HGGs and BM. In this review, we emphasize on neuro-immunotherapy and the versatility of these biomimetic nano-delivery strategies for precise targeting of hard-to-treat and most lethal HGGs and BM. Moreover, the challenges impeding the clinical translatability of these approaches were addressed to unmet medical needs of brain cancers.
{"title":"Immune response recalibration using immune therapy and biomimetic nano-therapy against high-grade gliomas and brain metastases","authors":"Puja Sandhbor , Geofrey John , Sakshi Bhat , Jayant S. Goda","doi":"10.1016/j.ajps.2025.101021","DOIUrl":"10.1016/j.ajps.2025.101021","url":null,"abstract":"<div><div>Although with aggressive standards of care like surgical resection, chemotherapy, and radiation, high-grade gliomas (HGGs) and brain metastases (BM) treatment has remained challenging for more than two decades. However, technological advances in this field and immunotherapeutic strategies have revolutionized the treatment of HGGs and BM. Immunotherapies like immune checkpoint inhibitors, CAR-T targeting, oncolytic virus-based therapy, bispecific antibody treatment, and vaccination approaches, etc., are emerging as promising avenues offering new hope in refining patient's survival benefits. However, selective trafficking across the blood-brain barrier (BBB)<em>,</em> immunosuppressive tumor microenvironment (TME), metabolic alteration, and tumor heterogeneity limit the therapeutic efficacy of immunotherapy for HGGs and BM. Furthermore, to address this concern, the NanoBioTechnology-based bioinspired delivery system has been gaining tremendous attention in recent years. With technological advances such as Trojan horse targeting and infusing/camouflaging nanoparticles surface with biological molecules/cells like immunocytes, erythrocytes, platelets, glioma cell lysate and/or integrating these strategies to get hybrid membrane for homotypic recognition. These biomimetic nanotherapy offers advantages over conventional nanoparticles, focusing on greater target specificity, increased circulation stability, higher active loading capacity, BBB permeability (inherent inflammatory chemotaxis of neutrophils), decreased immunogenicity, efficient metabolism-based combinatorial effects, and prevention of tumor recurrence by induction of immunological memory, etc. provide new age of improved immunotherapies outcomes against HGGs and BM. In this review, we emphasize on neuro-immunotherapy and the versatility of these biomimetic nano-delivery strategies for precise targeting of hard-to-treat and most lethal HGGs and BM. Moreover, the challenges impeding the clinical translatability of these approaches were addressed to unmet medical needs of brain cancers.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 2","pages":"Article 101021"},"PeriodicalIF":10.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10DOI: 10.1016/j.ajps.2025.101020
Xuan Huang , Kudelaidi Kuerban , Jajun Fan , Danjie Pan , Huaning Chen , Jiayang Liu , Songna Wang , Dianwen Ju , Yi Zhun Zhu , Jiyong Liu , Li Ye
Immunotherapy with interleukin-2 (IL-2) in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise. To address these challenges, IL-2-So-Lipo, a novel liposomal formulation combining IL-2 with sorafenib derivative, was developed as an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles in tumor growth. Sorafenib derivatives could target at melanoma-specific receptors, further enhancing liposomal specificity at the tumor site. Our results demonstrated that the prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared to IL-2 or sorafenib monotherapies, as well as their combination. In a B16F10 melanoma model, IL-2-So-Lipo was found to significantly inhibit tumor progression (tumor volume of 108.01 ± 62.99 mm3) compared to the control group (tumor volume of 1,397.13 ± 75.55 mm3), improving the therapeutic efficacy. This enhanced efficacy is attributed to the targeted delivery of IL-2 which promoted the infiltration and activation of cytotoxic T lymphocytes. Additionally, liposomal encapsulation of sorafenib derivatives enhanced its delivery efficiency, promoting tumor cell apoptosis and suppressing angiogenesis. Mechanistically, IL-2-So-Lipo could kill tumors by inducing a shift towards an anti-tumor immune response via facilitating the polarization of macrophages towards the M1 phenotype. Furthermore, IL-2-So-Lipo downregulated several key proteins in the MAPK signaling pathway, exerting a significant role in mediating tumor resistance to sorafenib. These findings underscore the potential of IL-2-So-Lipo as a promising strategy to improve the therapeutic efficacy of immunotherapy and targeted therapy in cancers. Moreover, the combination of IL-2 and sorafenib in a liposomal delivery system overcame the limitations of conventional IL-2 therapy, offering a synergistic approach to improve therapeutic outcomes for solid tumors.
白细胞介素-2 （IL-2）在治疗癌症中的免疫疗法受到一些限制，如全身副作用和对低免疫细胞浸润的肿瘤的疗效降低，尽管它很有希望。为了解决这些挑战，IL-2- so - lipo是一种新型的脂质体制剂，将IL-2与索拉非尼衍生物结合，作为一种抗血管生成药物，抑制新血管的生长，而新血管在肿瘤生长中起着至关重要的作用。索拉非尼衍生物可以靶向黑色素瘤特异性受体，进一步增强肿瘤部位脂质体的特异性。我们的研究结果表明，与IL-2或索拉非尼单药及其联合治疗相比，制备的IL-2- so - lipo的抗肿瘤活性显著增强。在B16F10黑色素瘤模型中，IL-2-So-Lipo明显抑制肿瘤进展（肿瘤体积为108.01±62.99 mm3），而对照组（肿瘤体积为1379.13±75.55 mm3），提高了治疗效果。这种增强的功效归因于靶向递送IL-2，促进细胞毒性T淋巴细胞的浸润和活化。此外，索拉非尼衍生物脂质体包封可提高其递送效率，促进肿瘤细胞凋亡，抑制血管生成。在机制上，IL-2-So-Lipo可以通过促进巨噬细胞向M1表型极化，诱导向抗肿瘤免疫反应的转变来杀死肿瘤。此外，IL-2-So-Lipo下调MAPK信号通路中的几个关键蛋白，在介导肿瘤对索拉非尼的耐药中发挥重要作用。这些发现强调了IL-2-So-Lipo作为提高癌症免疫治疗和靶向治疗疗效的有希望的策略的潜力。此外，IL-2和索拉非尼在脂质体递送系统中的联合使用克服了传统IL-2治疗的局限性，为改善实体瘤的治疗结果提供了一种协同方法。
{"title":"IL-2-loaded liposomes modified with sorafenib derivative exert a synergistic anti-melanoma effect via improving tumor immune microenvironment and enhancing antiangiogenic activity","authors":"Xuan Huang , Kudelaidi Kuerban , Jajun Fan , Danjie Pan , Huaning Chen , Jiayang Liu , Songna Wang , Dianwen Ju , Yi Zhun Zhu , Jiyong Liu , Li Ye","doi":"10.1016/j.ajps.2025.101020","DOIUrl":"10.1016/j.ajps.2025.101020","url":null,"abstract":"<div><div>Immunotherapy with interleukin-2 (IL-2) in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise. To address these challenges, IL-2-So-Lipo, a novel liposomal formulation combining IL-2 with sorafenib derivative, was developed as an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles in tumor growth. Sorafenib derivatives could target at melanoma-specific receptors, further enhancing liposomal specificity at the tumor site. Our results demonstrated that the prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared to IL-2 or sorafenib monotherapies, as well as their combination. In a B16F10 melanoma model, IL-2-So-Lipo was found to significantly inhibit tumor progression (tumor volume of 108.01 ± 62.99 mm<sup>3</sup>) compared to the control group (tumor volume of 1,397.13 ± 75.55 mm<sup>3</sup>), improving the therapeutic efficacy. This enhanced efficacy is attributed to the targeted delivery of IL-2 which promoted the infiltration and activation of cytotoxic T lymphocytes. Additionally, liposomal encapsulation of sorafenib derivatives enhanced its delivery efficiency, promoting tumor cell apoptosis and suppressing angiogenesis. Mechanistically, IL-2-So-Lipo could kill tumors by inducing a shift towards an anti-tumor immune response via facilitating the polarization of macrophages towards the M1 phenotype. Furthermore, IL-2-So-Lipo downregulated several key proteins in the MAPK signaling pathway, exerting a significant role in mediating tumor resistance to sorafenib. These findings underscore the potential of IL-2-So-Lipo as a promising strategy to improve the therapeutic efficacy of immunotherapy and targeted therapy in cancers. Moreover, the combination of IL-2 and sorafenib in a liposomal delivery system overcame the limitations of conventional IL-2 therapy, offering a synergistic approach to improve therapeutic outcomes for solid tumors.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 2","pages":"Article 101020"},"PeriodicalIF":10.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10DOI: 10.1016/j.ajps.2025.101019
Fuya Jia , Xiaoxing Fan , Licheng Wu , Yating Wang , Jisen Zhang , Zhou Zhou , Lian Li , Jingyuan Wen , Yuan Huang
Solid lipid nanoparticles (SLN) could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport. Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment. They are mainly transported by oligopeptide transporter-1 (PepT-1) which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption. Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway. This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation. Herein, two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1 (GLP-1) analogue exenatide as model drugs. These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6 mice and type II diabetic KKAy mice. Compared with un-modified SLN, dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake. Interestingly, after internalization, more SLN could access the systemic circulation via lymphatic transport pathway, highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.
{"title":"Enhanced lymphatic transportation of SLN by mimicking oligopeptide transportation route","authors":"Fuya Jia , Xiaoxing Fan , Licheng Wu , Yating Wang , Jisen Zhang , Zhou Zhou , Lian Li , Jingyuan Wen , Yuan Huang","doi":"10.1016/j.ajps.2025.101019","DOIUrl":"10.1016/j.ajps.2025.101019","url":null,"abstract":"<div><div>Solid lipid nanoparticles (SLN) could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport. Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment. They are mainly transported by oligopeptide transporter-1 (PepT-1) which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption. Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway. This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation. Herein, two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1 (GLP-1) analogue exenatide as model drugs. These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6 mice and type II diabetic KKAy mice. Compared with un-modified SLN, dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake. Interestingly, after internalization, more SLN could access the systemic circulation via lymphatic transport pathway, highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 3","pages":"Article 101019"},"PeriodicalIF":10.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106382","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 : 2025-01-10DOI: 10.1016/j.ajps.2025.101018
Chen Su , Jianhan Lin , Cong Li , Xinyu Wang , Donghui Pan , Lizhen Wang , Yuping Xu , Chongyang Chen , Kangfan Ji , Jinqiang Wang , Daozhen Chen , Min Yang , Zhen Gu , Junjie Yan
Nitric oxide (NO) modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies. Although a nanoengineering strategy has been proposed to overcome deficiencies of NO gas or small NO donor molecules, such as short half-life, lipophilicity, non-selectivity, and poor stability, it remains challenging to prepare NO nanomedicines with simple composition, multiple functions and enhanced therapeutic efficacy. Herein, we build a liquid metal nanodroplet (LMND)-based NO nanogenerator (LMND@HSG) that is stabilized by a bioreducible guanylated hyperbranched poly(amido amine) (HSG) ligand. Mechanically, the tumor microenvironment specifically triggers a cascade process of glutathione elimination, reactive oxygen species (ROS) generation, and NO release. According to actual demand, the ROS and NO concentrations could be readily controlled by tuning the LMND and HSG feed amounts. Along with the intrinsic anticancer property of LMND (ROS-mediated apoptosis and anti-angiogenesis), LMND@HSG administration could further enhance tumor growth suppression compared with LMND and HSG alone. From this study, leveraging LMND for NO gas therapy provides more possibilities for the prospect of LMND-based anticancer nanomedicines.
{"title":"Tumor-specific liquid metal nitric oxide nanogenerator for enhanced breast cancer therapy","authors":"Chen Su , Jianhan Lin , Cong Li , Xinyu Wang , Donghui Pan , Lizhen Wang , Yuping Xu , Chongyang Chen , Kangfan Ji , Jinqiang Wang , Daozhen Chen , Min Yang , Zhen Gu , Junjie Yan","doi":"10.1016/j.ajps.2025.101018","DOIUrl":"10.1016/j.ajps.2025.101018","url":null,"abstract":"<div><div>Nitric oxide (NO) modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies. Although a nanoengineering strategy has been proposed to overcome deficiencies of NO gas or small NO donor molecules, such as short half-life, lipophilicity, non-selectivity, and poor stability, it remains challenging to prepare NO nanomedicines with simple composition, multiple functions and enhanced therapeutic efficacy. Herein, we build a liquid metal nanodroplet (LMND)-based NO nanogenerator (LMND@HSG) that is stabilized by a bioreducible guanylated hyperbranched poly(amido amine) (HSG) ligand. Mechanically, the tumor microenvironment specifically triggers a cascade process of glutathione elimination, reactive oxygen species (ROS) generation, and NO release. According to actual demand, the ROS and NO concentrations could be readily controlled by tuning the LMND and HSG feed amounts. Along with the intrinsic anticancer property of LMND (ROS-mediated apoptosis and anti-angiogenesis), LMND@HSG administration could further enhance tumor growth suppression compared with LMND and HSG alone. From this study, leveraging LMND for NO gas therapy provides more possibilities for the prospect of LMND-based anticancer nanomedicines.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 2","pages":"Article 101018"},"PeriodicalIF":10.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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