Asian Journal of Pharmaceutical Sciences最新文献

{"title":"Inhalable stem cell-derived artificial nanovesicles for targeted siRNA delivery to effectively alleviate asthma symptoms","authors":"Shihan Chen ,&nbsp;Ruyi Lin ,&nbsp;Yuhuan Kong ,&nbsp;Hao Sun ,&nbsp;Jiawen Wang ,&nbsp;Jinsong Zhang ,&nbsp;Yanshuang Huang ,&nbsp;Honghui Wu ,&nbsp;Donghang Xu ,&nbsp;Jianqing Gao ,&nbsp;Tianyuan Zhang","doi":"10.1016/j.ajps.2026.101122","DOIUrl":"10.1016/j.ajps.2026.101122","url":null,"abstract":"<div><div>Asthma, one of the most prevalent chronic inflammatory diseases, remains challenging to manage effectively. Current therapies commonly alleviate symptoms through broad immunosuppression and bronchodilation but fail to target disease-specific molecular pathways. Genetic intervention using small interfering RNA (siRNA) has emerged as a promising strategy for asthma therapy. However, its success is largely hindered by the lack of an efficient delivery approach targeting airway epithelial cells (AECs). Here, we developed a novel inhalable siRNA delivery system based on artificially prepared nanovesicles through designed extrusion processes of mesenchymal stem cells. To enable an effective inhalation delivery of siRNA <em>via</em> nanovesicles, various parameters, including extrusion cycles, membrane pore sizes, and centrifugal forces were examined through orthogonal testing. Results revealed that the artificially prepared nanovesicles demonstrated remarkable capability to deliver thymic stromal lymphopoietin-targeted siRNA into AECs and substantially suppressed the inflammatory pathways and goblet cell hyperplasia, and eventually achieved a significant inhibition of asthma symptoms in ovalbumin-induced asthma models. Thus, the present study provides a novel nebulized nanovesicle-based carrier for effective delivery of siRNA through local inhalation, offering a promising therapeutic delivery platform for asthma and potentially other respiratory diseases.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"21 1","pages":"Article 101122"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147385427","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}

{"title":"High-dose treatment of cathepsin B-activatable doxorubicin prodrug nanoparticles that induce tumor-specific immunogenic cell death for immunotherapy of melanoma with minimal systemic toxicity","authors":"Yoojeong Oh ,&nbsp;Jinseong Kim ,&nbsp;Nayeon Shim ,&nbsp;Hyeonji Yoo ,&nbsp;Hoyeon Lee ,&nbsp;Yumin Jeong ,&nbsp;Jagyeong Goo ,&nbsp;Jeongyeon Lee ,&nbsp;Mihee Jo ,&nbsp;Hanhee Cho ,&nbsp;Kwangmeyung Kim","doi":"10.1016/j.ajps.2026.101123","DOIUrl":"10.1016/j.ajps.2026.101123","url":null,"abstract":"<div><div>Highly potent chemotherapy provides rapid therapeutic efficacy in melanoma, but is often limited by drug resistance, off-target toxicity, and systemic toxicity. Combination therapy with chemotherapy and immunotherapy has attracted much attention but still faces challenges such as inconsistent immune responses and systemic toxicity. To address these limitations, we developed cathepsin B-activatable doxorubicin (DOX) prodrug nanoparticles (CatB-NPs) for inducing tumor-specific immunogenic cell death (ICD), while minimizing off-target toxicity in normal tissues with low cathepsin B expression. The cathepsin B-activatable DOX prodrug was synthesized by conjugating the cathepsin B-cleavable peptide (FRRL) to DOX, yielding FRRL-DOX. The amphiphilic FRRL-DOX formed stable nanoparticles (163.6 ± 13.5 nm) through intermolecular hydrophobic interaction and π<em>-</em>π stacking. In melanoma cells overexpressing cathepsin B, CatB-NPs effectively induced cancer cell-specific ICD, while sparing normal cells and immune cells. When CatB-NPs-treated B16F10 cells were co-cultured with immune cells, CatB-NPs enhanced the phagocytic activity of macrophages and induced the maturation of dendritic cells (DCs). In melanoma models, CatB-NPs passively accumulated at tumor tissues through the enhanced permeability and retention effect and were selectively activated by intratumoral cathepsin B, enabling high-dose treatment that induced robust ICD. Importantly, combination therapy with CatB-NPs and anti-PD-L1 antibody enhanced ICD, DC maturation and T-cell activation, resulting in complete tumor regression in 50% of treated mice by converting the immunosuppressive tumor environment into an immune-responsive state. In a lung metastasis model, high-dose CatB-NPs with anti-PD-L1 also suppressed metastatic burden without systemic toxicity, supporting their potential as a safe and effective chemo-immunotherapy for melanoma.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"21 1","pages":"Article 101123"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098714","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}

{"title":"A novel mRNA nanovaccine with dual immunoregulation ameliorates rheumatoid arthritis and associated pneumonia","authors":"Jingjing Su ,&nbsp;Wenguang Huang ,&nbsp;Wenying Zhang ,&nbsp;Ziyi Wang ,&nbsp;Hongzhou Gu ,&nbsp;Pengchao Sun ,&nbsp;Yongxing Zhao","doi":"10.1016/j.ajps.2026.101120","DOIUrl":"10.1016/j.ajps.2026.101120","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) as a systemic autoimmune disease, frequently triggers various extra-articular symptoms, particularly the RA-associated pneumonia. Unfortunately, the RA-associated pneumonia has garnered insufficient attention, and conventional RA therapies may exacerbate pneumonia-related complications, thereby complicating the treatment process. Herein, a novel dual immunoregulatory mRNA nanovaccine (MPDA@RC@HM) is designed for the efficient treatment of RA and RA-associated pneumonia simultaneously. This innovative mRNA nanovaccine represents a highly organized nanostructure that integrates the rapamycin-loaded mesoporous polydopamine (MPDA) with mRNA encoding the epitope of type Ⅱ collagen, and the surface is modified with hyaluronic acid and dendritic cell membrane. After intravenous injection into collagen-induced arthritis mice, the mRNA nanovaccine exhibits effective distribution and transfection within the spleen and lung, subsequently exerting potent immunoregulation in both organs, thereby yielding a dual therapeutic effect. This study presents a versatile mRNA nanovaccine platform for the treatment of autoimmune diseases and provides an innovative approach for addressing RA and RA-associated pneumonia.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"21 1","pages":"Article 101120"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098727","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}

{"title":"From bench to bedside: Unveiling the background and benefits of nanovaccines tested in clinics","authors":"Vera S. Egorova ,&nbsp;Ekaterina P. Kolesova ,&nbsp;Maya V. Voronina ,&nbsp;Evgenya R. Denisova ,&nbsp;Anastasiia O. Syrocheva ,&nbsp;Tatiana Pallaeva ,&nbsp;Mazdak G. Hakemi ,&nbsp;Andrey A. Zamyatnin ,&nbsp;Konstantin I. Ivanov ,&nbsp;Dmitry Kostyushev ,&nbsp;Sergey Brezgin ,&nbsp;Anastasiia Kostyusheva ,&nbsp;Alessandro Parodi","doi":"10.1016/j.ajps.2026.101116","DOIUrl":"10.1016/j.ajps.2026.101116","url":null,"abstract":"<div><div>Despite the growing body of literature on nanovaccines, focused analyses of platforms tested in and undergoing clinical investigation remain limited. This review addresses this gap by critically examining recent advancements and highlighting nanovaccine technologies that have undergone human clinical trials. Using an extensive search on <span><span>clinicaltrials.org</span><svg><path></path></svg></span>, we explored the diverse applications of nanovaccines, including leading SARS-CoV-2 candidates and platforms targeting other infectious diseases and cancers. We also highlighted foundational research that has enabled clinical investigation of nanovaccines over the past decade, highlighting their potential to address a range of medical conditions. While many technologies have been developed to combat SARS-CoV-2, several key innovations targeted a broader spectrum of diseases. This review details these technologies, focusing on their materials and mechanisms of action in inducing immune protection, while also exploring how nanomedicine facilitates nanovaccine development and introduces novel adjuvant concepts. Finally, we provided a retrospective analysis of the development journey of these platforms, offering insights into the intellectual and technological efforts behind their clinical translation. By bridging the gap between research and application, this review aims to give readers a comprehensive understanding of how nanovaccines progress from the laboratory to clinical practice.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"21 1","pages":"Article 101116"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147385413","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}

{"title":"The evolution of lipid nanoparticles: Paving the way for next-generation nucleic acid medicines","authors":"Xuan Lin ,&nbsp;Hongguang Xiang ,&nbsp;Jiong Wu ,&nbsp;Ruixi Liao ,&nbsp;Yuhao Li ,&nbsp;Bohui Xu ,&nbsp;Ying Xu ,&nbsp;Yan Shen ,&nbsp;Qian Li ,&nbsp;Yu Tian","doi":"10.1016/j.ajps.2026.101121","DOIUrl":"10.1016/j.ajps.2026.101121","url":null,"abstract":"<div><div>Nucleic acid-based therapies have emerged as promising strategies for the regulation of gene expression and the production of therapeutic antigens or proteins for a series of diseases, including cancers, rare diseases, and infectious diseases. However, their clinical application faces challenges. These include high molecular weight, limited cellular uptake, and susceptibility to enzymatic degradation by nucleases <em>in vivo</em>. Both viral and non-viral delivery vectors have been developed as a means of addressing these limitations, including lipid nanoparticles (LNPs), exosomes, polymers, and inorganic nanoparticles. Among these, LNPs have garnered significant attention due to their superior biocompatibility, high delivery efficiency and customizable design potential, as demonstrated by the clinical success of the FDA-approved siRNA drug Onpattro®. The critical role of nucleic acid drug carriers is discussed in this review. It also outlines the major types of carriers under development and examines the advancements and applications in LNP-based systems for nucleic acid delivery. By conducting a review of recent advancements in LNP design, delivery mechanisms, and clinical applications, this article aims to clarify the ways in which LNPs overcome delivery barriers, compare LNPs with other carriers, and identify key trends that can inform the development of next-generation LNP platforms for nucleic acid therapeutics.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"21 1","pages":"Article 101121"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147385428","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}

{"title":"Exploring the frontier of oral nanomedicine in colorectal cancer therapy: Folate-targeted 5FU-Nisin-Selenium conjugates and probiotic-rich diets as a novel approach","authors":"Mozhgan Derakhshan-sefidi ,&nbsp;Bita Bakhshi ,&nbsp;Aliakbar Rasekhi ,&nbsp;Roya Saeidnejad","doi":"10.1016/j.ajps.2025.101106","DOIUrl":"10.1016/j.ajps.2025.101106","url":null,"abstract":"<div><div>This study aimed to assess the therapeutic potential of nisin, 5-fluorouracil (5FU) and selenium encapsulated in folate-conjugated thiolated chitosan nanoparticles (N/5FU/Se@FTCsNPs), combined with a probiotic cocktail of <em>Lactobacillus acidophilus</em> and <em>Bifidobacterium bifidum</em>, against colorectal cancer (CRC). The nanoparticles (277 nm, +9.2 mV) exhibited high drug loading efficiencies (5FU: 89.11 %, nisin: 70.68 %) and pH-responsive release, with minimal drug release under gastric conditions and ∼60.7 % release at colonic pH, facilitating targeted delivery. The formulation remained stable for over 40 d at −20 °C and 4 °C, demonstrating excellent biocompatibility (&lt;2 % hemolysis) and exhibiting strong mucoadhesive and mucus-penetrating abilities. <em>In vitro</em>, N/5FU/Se@FTCsNPs selectively targeted CT26 colon cancer cells (IC₅₀: 1.57 µg/ml) with minimal effects on healthy cells, enhanced cellular uptake, and induced ROS-mediated apoptosis. <em>In vivo</em>, oral administration—especially with probiotics—significantly reduced tumor volume, improved survival rates and alleviated chemotherapy-related side effects such as diarrhea and weight loss. Biodistribution studies confirmed increased tumor targeting and decreased off-target exposure. Mechanistically, the treatment downregulated oncogenes and inflammatory markers (2- to 12.5-fold), including <em>β-catenin, mTOR, COX-2</em> and <em>VEGF-α</em>, while upregulating tumor suppressors and protective genes (4 to 14.8 fold), such as <em>PTEN, CASP9</em> and <em>Mucin 2</em> (<em>P</em> &lt; 0.0001). This indicates inhibition of proliferation, metastasis, inflammation, and angiogenesis, along with improved gut barrier function. Cytokine profiling and histological analysis further confirmed reduced systemic inflammation and maintained hematological safety. These findings highlight N/5FU/Se@FTCsNPs combined with probiotics as a promising, safe and effective oral therapy for CRC, leveraging microbiota modulation and targeted delivery.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 6","pages":"Article 101106"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691629","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}

{"title":"Integrating CRISPR/Cas technology with clinical trials: Principles, progress and challenges","authors":"Piao Yang ,&nbsp;Mohadeseh Khoshandam ,&nbsp;Iman Bhia ,&nbsp;Sevil Raji ,&nbsp;Hossein Soltaninejad ,&nbsp;Saman Hosseinkhani ,&nbsp;Mehdi Sani ,&nbsp;Amir Ali Hamidieh ,&nbsp;Mohsen Sheykhhasan","doi":"10.1016/j.ajps.2025.101068","DOIUrl":"10.1016/j.ajps.2025.101068","url":null,"abstract":"<div><div>CRISPR represent a groundbreaking genome-editing technology that has revolutionized genetic modification. This innovative tool offers an unparalleled revolution in the future treatment of genetic disorders, neurological diseases, infectious diseases and cancer. Despite the rapid expansion of CRISPR applications, its clinical use in humans is still relatively limited, with only 69 active clinical trials and 6 completed studies reported so far. This review examined current clinical trials and their processes in addressing various diseases via the CRISPR/Cas system. While earlier literatures have focused mainly on delivery methods and materials for CRISPR/Cas9, our review emphasized innovative targeting conditions and approaches for novel and functional therapeutic designs. In addition, we reviewed recent research to increase the efficiency of CRISPR editing in the management of genetic disorders and cancer, while exploring their future challenges and potential. This review provided a unique perspective on the advancement of CRISPR technology. By addressing these aspects, we aim to contribute to ongoing efforts to improve CRISPR-based therapies and expand their clinical applications, ultimately striving to transform the future of medical treatment.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 6","pages":"Article 101068"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622883","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}

{"title":"Biomaterials-mediated sequential drug delivery: Emerging trends for wound healing","authors":"Yuchuan Shi ,&nbsp;Shuaichen Guo ,&nbsp;Jiayi Tian ,&nbsp;Xi Xie ,&nbsp;Jie Shi ,&nbsp;Xing Zhang ,&nbsp;Chenchao Wang","doi":"10.1016/j.ajps.2025.101088","DOIUrl":"10.1016/j.ajps.2025.101088","url":null,"abstract":"<div><div>Wound healing is a series of complex biological events that are tightly coordinated by the body. However, this physiological process is compromised in a pathological setting and underlie conditions including diabetic complications, infectious diseases and chronic inflammatory conditions. Clinically, this translates to multiple pathological features collectively exhibited (microbial colonization, chronic inflammation and impaired regenerative processes). Due to these pathological features, modern wound care approaches have changed from simple passive coverage products to advanced dressing systems which incorporate multifunctional therapies. To comprehensively elucidate recent advancements in advanced wound dressings for drug delivery applications, this review systematically examines material-driven drug release strategies through multiple analytical dimensions. The discussion encompasses structurally engineered controlled-release systems featuring bilayer architectures, layer-by-layer assembly techniques and porous matrix designs, as well as intelligent stimulus-responsive mechanisms based on physicochemical properties, including physical condition modulation, swelling/degradation behavior control, dynamic chemical bond engineering and crosslinking network optimization. Through critical analysis of these cutting-edge technologies, this article provides insightful perspectives on their clinical translation potential and future trajectories.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 6","pages":"Article 101088"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691627","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}

{"title":"The strategies and advances of mRNA translation booster","authors":"Yingying Shi ,&nbsp;Kedong Sun ,&nbsp;Yilong Hu ,&nbsp;Zeliang Lou ,&nbsp;Yi Wang ,&nbsp;Jian You","doi":"10.1016/j.ajps.2025.101090","DOIUrl":"10.1016/j.ajps.2025.101090","url":null,"abstract":"<div><div>The therapeutic efficacy and safety of mRNA-based drugs in immunological and nonimmunological applications are critically dependent on the translated protein yield, which requires precise modulation of mRNA expression kinetics. Among the factors influencing mRNA translation, immunogenicity and stability are pivotal in determining the longevity of protein production. Current optimization strategies have integrated (1) molecular engineering (<em>e.g.</em>, modified nucleotides), (2) advanced delivery systems (<em>e.g.</em>, lipid nanoparticles), and (3) adjuvant drug synergy. This review focuses on co-delivered adjuvant drugs and introduces the concept of \"mRNA translation boosters\" for the first time. mRNA translation boosters are classified as small-molecule compounds and macromolecular agents that improve translational fidelity through mechanisms including blockade of pattern recognition receptors, modulation of inflammatory cascades, facilitation of endosomal escape, and protection against enzymatic degradation. As clinically validated with COVID-19 mRNA vaccines, these boosters have now demonstrated expanded utility in gene editing therapies and protein replacement applications. This review addresses the immunological challenges encountered during mRNA transfection and translation while summarizing existing mRNA translation boosters that optimize protein expression kinetics. By establishing a mechanistic framework for booster selection and employment, this work provides translational guidance for advancing nucleic acid therapeutics towards their maximum clinical potential.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 6","pages":"Article 101090"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691628","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}

{"title":"A ROS/photo dual-responsive prodrug unimolecular micelle for boosted cancer immunotherapy","authors":"Zeqian Huang ,&nbsp;Congjun Xu ,&nbsp;Yaqing Ding ,&nbsp;Zishan Zeng ,&nbsp;Huanxin Lin ,&nbsp;Yong Luo ,&nbsp;Xiaoyu Xu ,&nbsp;Yanjuan Huang ,&nbsp;Chunshun Zhao","doi":"10.1016/j.ajps.2025.101104","DOIUrl":"10.1016/j.ajps.2025.101104","url":null,"abstract":"<div><div>Integrating photodynamic therapy (PDT) with immunosuppression reversal represents a promising synergistic approach to boost cancer immunotherapy. However, the complicated components and cumbersome preparation procedures of the currently developed nano drug delivery systems heavily hinder their further clinical translation. Herein, a reactive oxygen species (ROS)/photo dual-responsive amphipathic prodrug (denoted as PPTN) was designed and synthesized by linking NLG919, an indoleamine-2,3-dioxygenase (IDO) inhibitor, with the photosensitizer protoporphyrin IX (PpIX) by a thioketal moiety, and further modifying with mPEG_2k. PPTN could self-assemble into nanoscale unimolecular micelles in aqueous solution without additional excipients, increasing tumor accumulation while effectively addressing the pronounced hydrophobicity challenge of PpIX. Upon light exposure, PPTN generated ROS, not only directly damaging cancer cells, but also trigger the breakage of thioketal bond to accelerate simultaneous release of NLG919. Therefore, PPTN potentially act as a promising ROS/photo dual-responsive carrier-free prodrug delivery system for controllable drug release and specific tumor therapy. Moreover, PPTN induced simultaneous PDT-triggered immunogenic cell death (ICD) effect and specific IDO blockade to boost immune response, exhibiting potent suppression efficacy against primary and distant tumors. Overall, with the superiorities of easily controllable preparation procedures, synchronous drug delivery and ROS/photo dual-responsiveness, such a prodrug unimolecular micelle may represent a promising nanoplatform for photoactivated-immunotherapy.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 6","pages":"Article 101104"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691624","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}