Asian Journal of Pharmaceutical Sciences最新文献

{"title":"In situ injectable hydrogel encapsulating Mn/NO-based immune nano-activator for prevention of postoperative tumor recurrence","authors":"Shengnan Huang ,&nbsp;Chenyang Zhou ,&nbsp;Chengzhi Song ,&nbsp;Xiali Zhu ,&nbsp;Mingsan Miao ,&nbsp;Chunming Li ,&nbsp;Shaofeng Duan ,&nbsp;Yurong Hu","doi":"10.1016/j.ajps.2024.100901","DOIUrl":"10.1016/j.ajps.2024.100901","url":null,"abstract":"<div><p>Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an <em>in situ</em> injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO₂ shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn²⁺ and produce O₂, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn²⁺ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of <em>in situ</em> injectable hydrogels in preventing postoperative tumor recurrence.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 2","pages":"Article 100901"},"PeriodicalIF":10.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000187/pdfft?md5=b3681e2629d372d806369b0a30484239&pid=1-s2.0-S1818087624000187-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140053695","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}

{"title":"Fine-tuning the activation behaviors of ternary modular cabazitaxel prodrugs for efficient and on-target oral anti-cancer therapy","authors":"Mingyang Zhang ,&nbsp;Yifan Miao ,&nbsp;Can Zhao ,&nbsp;Tong Liu ,&nbsp;Xiyan Wang ,&nbsp;Zixuan Wang ,&nbsp;Wenxin Zhong ,&nbsp;Zhonggui He ,&nbsp;Chutong Tian ,&nbsp;Jin Sun","doi":"10.1016/j.ajps.2024.100908","DOIUrl":"10.1016/j.ajps.2024.100908","url":null,"abstract":"<div><p>The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (<em>e.g.</em>, ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 2","pages":"Article 100908"},"PeriodicalIF":10.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000254/pdfft?md5=7707ff414e46d464a681359d4b689802&pid=1-s2.0-S1818087624000254-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140402283","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}

{"title":"Ionic liquids as the effective technology for enhancing transdermal drug delivery: Design principles, roles, mechanisms, and future challenges","authors":"Xuejun Chen ,&nbsp;Ziqing Li ,&nbsp;Chunrong Yang ,&nbsp;Degong Yang","doi":"10.1016/j.ajps.2024.100900","DOIUrl":"10.1016/j.ajps.2024.100900","url":null,"abstract":"<div><p>Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of action mechanisms remain to be explored. In this review, basic design principles of ideal ILs for transdermal drug delivery system (TDDS) are discussed considering melting point, skin permeability, and toxicity, which depend on the molar ratios, types, functional groups of ions and inter-ionic interactions. Secondly, the contributions of ILs to the development of TDDS through different roles are described: as novel skin penetration enhancers for enhancing transdermal absorption of drugs; as novel solvents for improving the solubility of drugs in carriers; as novel active pharmaceutical ingredients (API-ILs) for regulating skin permeability, solubility, release, and pharmacokinetic behaviors of drugs; and as novel polymers for the development of smart medical materials. Moreover, diverse action mechanisms, mainly including the interactions among ILs, drugs, polymers, and skin components, are summarized. Finally, future challenges related to ILs are discussed, including underlying quantitative structure-activity relationships, complex interaction forces between anions, drugs, polymers and skin microenvironment, long-term stability, and <em>in vivo</em> safety issues. In summary, this article will promote the development of TDDS based on ILs.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 2","pages":"Article 100900"},"PeriodicalIF":10.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000175/pdfft?md5=68103cdbbcaa8d7bdbf76d01159caa5e&pid=1-s2.0-S1818087624000175-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140053771","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}

{"title":"Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy","authors":"Bao Li ,&nbsp;Haoran Niu ,&nbsp;Xiaoyun Zhao ,&nbsp;Xiaoyu Huang ,&nbsp;Yu Ding ,&nbsp;Ke Dang ,&nbsp;Tianzhi Yang ,&nbsp;Yongfeng Chen ,&nbsp;Jizhuang Ma ,&nbsp;Xiaohong Liu ,&nbsp;Keda Zhang ,&nbsp;Huichao Xie ,&nbsp;Pingtian Ding","doi":"10.1016/j.ajps.2024.100891","DOIUrl":"10.1016/j.ajps.2024.100891","url":null,"abstract":"<div><p>Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&amp;L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin α_vβ₃ overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 2","pages":"Article 100891"},"PeriodicalIF":10.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000084/pdfft?md5=2c347081a8dbfd835d0a999ae0e2260b&pid=1-s2.0-S1818087624000084-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139951662","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}

{"title":"Functionalized lipid nanoparticles modulate the blood-brain barrier and eliminate α-synuclein to repair dopamine neurons","authors":"Xiaomei Wu ,&nbsp;Renxiang Yuan ,&nbsp;Yichong Xu ,&nbsp;Kai Wang ,&nbsp;Hong Yuan ,&nbsp;Tingting Meng ,&nbsp;Fuqiang Hu","doi":"10.1016/j.ajps.2024.100904","DOIUrl":"10.1016/j.ajps.2024.100904","url":null,"abstract":"<div><p>The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential disease-modifying efficacy, have difficulty in crossing the blood-brain barrier (BBB) due to their large molecular weight. Herein, we fabricate multi-functionalized lipid nanoparticles (LNP) Lpc-BoSA/CSO with BBB targeting, permeability-increasing and responsive release functions. Borneol is chemically bonded with stearic acid and, as one of the components of Lpc-BoSA/CSO, is used to increase BBB permeability. Immunofluorescence results of brain tissue of 15-month-old C57BL/6 mice show that Lpc-BoSA/CSO disperses across the BBB into brain parenchyma, and the amount is 4.21 times greater than that of conventional LNP. Motor symptoms of mice in Lpc-BoSA/CSO-Exe group are significantly improved, and the content of dopamine is 1.85 times (substantia nigra compacta) and 1.49 times (striatum) that of PD mice. α-Synuclein expression and Lewy bodies deposition are reduced to 51.85% and 44.72% of PD mice, respectively. Immunohistochemical mechanism studies show AKT expression in Lpc-BoSA/CSO-Exe is 4.23 times that of PD mice and GSK-3β expression is reduced to 18.41%. Lpc-BoSA/CSO-Exe could reduce the production of α-synuclein and Lewy bodies through AKT/GSK-3β pathway, and effectively prevent the progressive deterioration of Parkinson's disease. In summary, Lpc-BoSA/CSO-Exe increases the entry of exenatide into brain and promotes its clinical application for Parkinson's disease therapy.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 2","pages":"Article 100904"},"PeriodicalIF":10.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000217/pdfft?md5=56dd1adb8e0df656c66b5e9ef3df6cef&pid=1-s2.0-S1818087624000217-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140150703","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}

{"title":"Targeting the organelle for radiosensitization in cancer radiotherapy","authors":"Xiaoyan Sun ,&nbsp;Linjie Wu ,&nbsp;Lina Du ,&nbsp;Wenhong Xu ,&nbsp;Min Han","doi":"10.1016/j.ajps.2024.100903","DOIUrl":"10.1016/j.ajps.2024.100903","url":null,"abstract":"<div><p>Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 2","pages":"Article 100903"},"PeriodicalIF":10.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000205/pdfft?md5=e0d13b60644e6971beba3e27b50ee960&pid=1-s2.0-S1818087624000205-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140150700","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}

{"title":"Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy","authors":"Xiaoju Guo ,&nbsp;Xiaoxiao Chen ,&nbsp;Jiayi Ding ,&nbsp;Feng Zhang ,&nbsp;Shunyang Chen ,&nbsp;Xin Hu ,&nbsp;Shiji Fang ,&nbsp;Lin Shen ,&nbsp;Chenying Lu ,&nbsp;Zhongwei Zhao ,&nbsp;Jianfei Tu ,&nbsp;Gaofeng Shu ,&nbsp;Minjiang Chen ,&nbsp;Jiansong Ji","doi":"10.1016/j.ajps.2024.100905","DOIUrl":"10.1016/j.ajps.2024.100905","url":null,"abstract":"<div><p>Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO₃ by a CaCO₃-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 2","pages":"Article 100905"},"PeriodicalIF":10.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000229/pdfft?md5=389fce3d0bd5602d04c3f1574d45f07d&pid=1-s2.0-S1818087624000229-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140204319","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}

{"title":"Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers","authors":"Xumei Ouyang ,&nbsp;Yu Liu ,&nbsp;Ke Zheng ,&nbsp;Zhiqing Pang ,&nbsp;Shaojun Peng","doi":"10.1016/j.ajps.2023.100883","DOIUrl":"10.1016/j.ajps.2023.100883","url":null,"abstract":"<div><p>Nanoscale drug delivery systems (nDDS) have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects. Although several nDDS have been successfully approved for clinical use up to now, biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment. Polyethylene glycol (PEG)-modification (or PEGylation) has been regarded as the gold standard for stabilising nDDS in complex biological environment. However, the accelerated blood clearance (ABC) of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications. Zwitterionic polymer, a novel family of anti-fouling materials, have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility. Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues. More impressively, zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution, pressure gradients, impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications. The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS, which could facilitate their better clinical translation. Herein, we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlying mechanisms. Finally, prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 1","pages":"Article 100883"},"PeriodicalIF":10.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087623001095/pdfft?md5=3e124350df384877710f4bb05396a70e&pid=1-s2.0-S1818087623001095-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139064458","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}

{"title":"Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices","authors":"Noehyun Myung,&nbsp;Hyun-Wook Kang","doi":"10.1016/j.ajps.2024.100884","DOIUrl":"10.1016/j.ajps.2024.100884","url":null,"abstract":"<div><p>Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer (TNBC), a highly aggressive disease with a poor prognosis. This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals, allowing for promising clinical outcomes with intensive treatment. However, the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance, limiting therapeutic efficacy and clinical benefit. Here, we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with time-programmed pulsatile release profiles. The implantable device can control the time between drug releases based on its internal microstructure design, which can be used to control dose density. The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar. Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects <em>in vitro</em> and <em>in vivo</em>. Under the same dose density conditions, device-based chemotherapy shows a higher anti-cancer effect and less toxic response than intratumoral injection. We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose, number of releases, and treatment duration of the dose-dense AC (doxorubicin and cyclophosphamide) regimen preferred for TNBC treatment. Dose density modulation inhibits tumor growth, metastasis, and the expression of drug resistance-related proteins, including p-glycoprotein and breast cancer resistance protein. To the best of our knowledge, local dose-dense chemotherapy has not been reported, and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 1","pages":"Article 100884"},"PeriodicalIF":10.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000011/pdfft?md5=7bbad6db8cc2163ee872827bb537c50b&pid=1-s2.0-S1818087624000011-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139465273","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}

{"title":"Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy","authors":"Chenglin Liang,&nbsp;Ge Zhang,&nbsp;Linlin Guo,&nbsp;Xinyi Ding,&nbsp;Heng Yang,&nbsp;Hongling Zhang,&nbsp;Zhenzhong Zhang,&nbsp;Lin Hou","doi":"10.1016/j.ajps.2024.100888","DOIUrl":"10.1016/j.ajps.2024.100888","url":null,"abstract":"<div><p>Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy, but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration. Herein, we designed a cancer-associated fibroblasts (CAFs) triggered structure-transformable nano-assembly (HSD-P@V), which can directionally deliver valsartan (Val, CAFs regulator) and doxorubicin (DOX, senescence inducer) to the specific targets. In detail, DOX is conjugated with hyaluronic acid (HA) via diselenide bonds (Se-Se) to form HSD micelles, while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer, which is coated on Val nanocrystals (VNs) surface for improving the stability and achieving responsive release. Once arriving at tumor microenvironment and touching CAFs, HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment. VNs can degrade the extracellular matrix, leading to the enhanced penetration of HSD. HSD targets tumor cells, releases DOX to induce senescence, and recruits effector immune cells. Furthermore, senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy. <em>In vitro</em> and <em>in vivo</em> results show that the nano-assembly remarkably inhibits tumor growth as well as lung metastasis, and extends tumor-bearing mice survival. This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 1","pages":"Article 100888"},"PeriodicalIF":10.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000059/pdfft?md5=4dadab8a85a615415f3f04021f25a240&pid=1-s2.0-S1818087624000059-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139816793","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}