Asian Journal of Pharmaceutical Sciences最新文献

{"title":"Targeted protein degradation with small molecules for cancer immunotherapy","authors":"Zichao Yang ,&nbsp;Jianwei Xu ,&nbsp;Xixiang Yang ,&nbsp;Jianjun Chen","doi":"10.1016/j.ajps.2025.101058","DOIUrl":"10.1016/j.ajps.2025.101058","url":null,"abstract":"<div><div>Immunotherapy has transformed cancer treatment, marked by the approval of numerous antibody-based drugs. However, the limitations of antibodies in pharmacokinetics including long half-lives, limited oral bioavailability and immunogenicity, have prompted the pursuit of small molecule-based immunotherapy. Traditional drug discovery strategies, which focus on blocking protein activity through inhibitors, face persistent hurdles, such as reliance on accessible binding pockets, poor selectivity, and the emergence of drug resistance. Targeted protein degradation (TPD) technologies have emerged as powerful tools to address these limitations, offering significant therapeutic advantages over conventional inhibition strategies, particularly for historically ''undruggable'' targets. In recent years, small molecule-based protein degraders have rapidly advanced in cancer immunotherapy. In this review, we highlight recent progress in TPD-driven small-molecule drug discovery and summarize the application of these technologies in cancer immunotherapy, including degraders targeting PD-1/PD-L1, chemokine receptors, IDO1, AhR, and others.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101058"},"PeriodicalIF":11.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Cerenkov radiation induced photodynamic therapy based on GSH-responsive biomimetic nanoplatform to trigger immunogenic cell death for tumor immunotherapy","authors":"Ruijie Qian ,&nbsp;Yawen Guo ,&nbsp;Xuemei Gao ,&nbsp;Jianzhuang Ren ,&nbsp;Dawei Jiang ,&nbsp;Rui An ,&nbsp;Ruihua Wang ,&nbsp;Xuhua Duan ,&nbsp;Xinwei Han","doi":"10.1016/j.ajps.2025.101070","DOIUrl":"10.1016/j.ajps.2025.101070","url":null,"abstract":"<div><div>Cerenkov radiation (CR) can serve as a source of internal light to overcome the limited tissue penetration of external light in conventional photodynamic therapy (PDT). However, insufficient luminescence intensity hinders the clinical application of CR-PDT. Here, we developed a glutathione-responsive biomimetic nanoplatform by fusing cancer cell membranes and liposomes loaded with photosensitizer hematoporphyrin monomethyl ether (HMME) and a radiation energy amplifier Eu³⁺, named HMME-Eu@LEV. Colloidal Eu³⁺ converts γ-radiation and CR from radioisotopes into fluorescence to enhance anti-tumor effects. Sequential administration ensures co-localization of HMME-Eu@LEV and radiopharmaceutical ¹⁸F-fluorodeoxyglucose (FDG) at the tumor site, triggering enhanced CR-PDT and immunogenic cell death. Our observations indicated that luminescence resonance energy transfer between Eu³⁺ and HMME was efficient, and Cerenkov luminescence from Eu@LEV+FDG was approximately 5.6-fold higher in intensity than that from FDG alone. As a result, abundant ROS were generated, and macrophages in the tumor microenvironment were polarized from M2 to M1. In addition, the immunosuppressive tumor microenvironment could be reversed by promoting the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes. The activated immune system effectively inhibited the growth of primary tumors and spread of distant metastases. Our work demonstrates the feasibility of CR-PDT without an external light source and the critical role of nanomaterials in personalized medicine.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101070"},"PeriodicalIF":10.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticles-incorporated hydrogel microneedle for biomedical applications: Fabrication strategies, emerging trends and future prospects","authors":"Zejun Xu ,&nbsp;Jiaying Chi ,&nbsp;Fei Qin ,&nbsp;Dongyan Liu ,&nbsp;Yecai Lai ,&nbsp;Yingxia Bao ,&nbsp;Ruizhi Guo ,&nbsp;Yiqiu liao ,&nbsp;Zhoufan Xie ,&nbsp;Jieqiong Jiang ,&nbsp;Juyan Liu ,&nbsp;Jianfeng Cai ,&nbsp;Chao Lu ,&nbsp;Jiansong Wang ,&nbsp;Chuanbin Wu","doi":"10.1016/j.ajps.2025.101069","DOIUrl":"10.1016/j.ajps.2025.101069","url":null,"abstract":"<div><div>Nanoparticles-incorporated hydrogel microneedles (NPs-HMN) have attracted significant attention due to their exceptional biomedical applications. The arrayed needle tips of NPs-HMN effectively penetrate the skin or tissue, enabling minimally invasive and painless delivery of therapeutic molecules into the tissue microenvironment. This approach has shown significant improvements in bioavailability and patient compliance. Moreover, the functionalized hydrogel materials of NPs-HMN exhibit a three-dimensional network structure resembling the extracellular matrix, along with controllable drug release, exceptional swelling ability, hydrophilicity, and biocompatibility. These characteristics broaden the potential applications of HMN in therapeutic and biosensing contexts. In addition, the incorporation of nanoparticles (NPs) has been shown to improve the solubility of hydrophobic drugs, enhance mechanical properties, enable intelligent drug release, and facilitate precise targeting of HMN. The versatility and diversity of treatment options afforded by NPs-HMN contribute to significant advancements in animal models and clinical settings, as well as offer valuable insights for biomaterial development. This review provides a comprehensive examination of the fabrication strategies of NPs-HMN and their recent advancements in biomedical applications. We also analyze the mechanisms, advantages, challenges, and future prospects of this system in enhancing drug delivery efficiency to provide theoretical references for further breakthroughs in novel delivery platforms.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101069"},"PeriodicalIF":11.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small molecular chelator for comprehensive regulation of tumor lactate levels in synergy with photodynamic therapy for cancer treatment","authors":"Haiqing Zhong ,&nbsp;Xufang Ying ,&nbsp;Xiaoyan Bao ,&nbsp;Linjie Wu ,&nbsp;Yiying Lu ,&nbsp;Qi Dai ,&nbsp;Qiyao Yang ,&nbsp;Xin Tan ,&nbsp;Donghang Xu ,&nbsp;Jianqing Gao ,&nbsp;Min Han","doi":"10.1016/j.ajps.2025.101059","DOIUrl":"10.1016/j.ajps.2025.101059","url":null,"abstract":"<div><div>An increasing number of studies have focused on depleting lactate and modulating the tumor's lactic microenvironment to interfere with tumor progression, particularly in breast cancer. Lactate accumulation in tumors contributes to a highly acidic microenvironment that promotes cancer cell survival and resistance to therapies. However, existing lactate depletion agents, primarily enzymes and macromolecules, fall short of clinical applications due to poor stability and their ability to only perform solitary lactate depletion without interfering with the transport process. Consequently, the development of stable molecules that deplete lactate and interfere with lactate transport is critically needed. Therefore, in this study, chlorin e6 (Ce6)-gadolinium chloride (GdCl₃)-flavin adenine dinucleotide (FAD)/tamoxifen (TAM) molecular chelates were prepared. The chelates fully interfered with lactate transport, depleted lactate in the tumor microenvironment, mitigated photodynamic therapy resistance, and realized synergistic photodynamic-hormonal therapy. FAD has promising capabilities in regulating lactate levels and mitigating acidic microenvironments. However, a strategy for depleting lactate by chelating the coenzyme FAD to form nanoparticles has not yet been reported. Tamoxifen disrupts tumor development and interferes with lactate transport by binding to estrogen receptor and inhibiting the expression of monocarboxylate transporter. In addition, coupling with Gd³⁺ increased the solubility of Ce6, thereby improving the photodynamic therapy effectiveness. This innovative strategy improves therapeutic efficacy and offers a promising approach for breast cancer treatment.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101059"},"PeriodicalIF":11.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721770","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":"Amphiphilic lipid-peptide engineered placenta-derived mesenchymal stem cells for liver fibrosis treatment","authors":"Hee Won Park ,&nbsp;Dae Hyun Lee ,&nbsp;Sungjun Kim ,&nbsp;Hyeri Park ,&nbsp;Ashok Kumar Jangid ,&nbsp;Chae Eun Lee ,&nbsp;Jaewon Park ,&nbsp;Gyu Tae Park ,&nbsp;Ha Yeon Park ,&nbsp;HyunJin Kim ,&nbsp;Jae Ho Kim ,&nbsp;Gi Jin Kim ,&nbsp;Kyobum Kim","doi":"10.1016/j.ajps.2025.101061","DOIUrl":"10.1016/j.ajps.2025.101061","url":null,"abstract":"<div><div>The global mortality rate due to liver diseases, particularly liver fibrosis, is increasing. Among various treatment methods, stem cell therapy using placenta-derived mesenchymal stem cells (PDMSCs) offers distinct benefits, including ease of isolation and superior proliferative potential. To enhance the therapeutic efficacy of PDMSCs, the WKYMVm peptide was selected for cell engineering. Immobilization of WKYMVm on PDMSC membranes facilitates effective peptide binding to the formyl peptide receptor 2 on adjacent PDMSCs and hepatocytes, thereby enhancing cell activation and achieving more efficient peptide utilization compared to bolus peptide treatment. Increased cell activation enhances the secretion of paracrine factors including growth factors and cytokines, which in turn improves liver function and vascular repair in both <em>in vitro</em> and <em>in vivo</em> models. This approach not only enhances the angiogenic and therapeutic capacities of stem cells, but also enables efficient peptide utilization, minimizing potential side effects and costs associated with high peptide dosages. Overall, our study demonstrates significant promise of stem cell therapy for treating liver fibrosis. Thus, stem cell therapy offers considerable prospects for clinical applications.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101061"},"PeriodicalIF":10.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in cell membrane-based biomimetic delivery systems for Parkinson’s disease: Perspectives and challenges","authors":"Jasleen Kaur ,&nbsp;Abhishek Thakran ,&nbsp;Saba Naqvi","doi":"10.1016/j.ajps.2025.101060","DOIUrl":"10.1016/j.ajps.2025.101060","url":null,"abstract":"<div><div>Neuroinflammation, α-synuclein pathology and dopaminergic cell loss are the hallmarks of Parkinson’s disease (PD), an incurable movement disorder. The presence of the blood-brain barrier (BBB) impedes the delivery of therapeutics and makes the design of drug-targeting delivery vehicles challenging. Nanomedicine is designed and has significantly impacted the scientific community. Over the last few decades, to address the shortcomings of synthetic nanoparticles, a new approach has emerged that mimic the physiological environment. Cell membrane-coated nanoparticles have been developed to interact with the physiological environment, enhance central nervous system drug delivery and mask toxic effects. Cell membranes are multifunctional, biocompatible platforms with the potential for surface modification and targeted delivery design. A synchronous design of cell membrane and nanoparticles is required for the cell membrane-based biomimetics, which can improve the BBB recognition and transport. This review summarizes the challenges in drug delivery and how cell membrane-coated nanoparticles can overcome them. Moreover, major cell membranes used in biomedical applications are discussed with a focus on PD.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101060"},"PeriodicalIF":11.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724244","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":"All-in-one peptide with sequential pH gradient sensing capabilities for the targeted delivery and deep penetration of nanomicelles against breast cancer","authors":"Qinying Chen ,&nbsp;Xinao Liu ,&nbsp;Zijin Tan ,&nbsp;Zhihao Liu ,&nbsp;Zijie Qiu ,&nbsp;Yerong Xiong ,&nbsp;Jiasheng Tu ,&nbsp;Yanping Wu ,&nbsp;Chunmeng Sun","doi":"10.1016/j.ajps.2025.101056","DOIUrl":"10.1016/j.ajps.2025.101056","url":null,"abstract":"<div><div>Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions, such as targeting delivery, tissue penetration and enhanced cellular uptake. However, a single ligand with multiple functions is generally preferred for use in practice. Herein, a versatile peptide, (HE)₁₀G₅R₆GDK (HE-RK), was engineered by integrating several motifs into a single sequence, including a masking segment (HE), a flexible linker (G₅), and a tumor-penetrating head (RK) which comprised a cell-penetrating peptide (R₆) and a C-end Rule peptide (RGDK). The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells. Moreover, in our study, polymer micelles conjugated with the HE-RK peptide (PM-HE-RK) showed superior cellular internalization at pH 6.5 compared to pH 7.4 <em>in vitro</em>, as well as extended blood circulation time and improved tumor targeting and penetration <em>in vivo</em>. Furthermore, the paclitaxel-loaded micelles (PTX/PM-HE-RK) demonstrated considerable antitumor efficacy, with an 81.48% tumor inhibition rate in the 4T1 mouse model. Overall, the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101056"},"PeriodicalIF":11.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721767","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":"Light-stimulated smart thermo-responsive constructs for enhanced wound healing: A streamlined command approach","authors":"Bingcheng Yi ,&nbsp;Lei Yu ,&nbsp;Yating Yang ,&nbsp;Carlos F. Guimarães ,&nbsp;Ruijie Xu ,&nbsp;Thavasyappan Thambi ,&nbsp;Boya Zhou ,&nbsp;Qihui Zhou ,&nbsp;Rui L. Reis","doi":"10.1016/j.ajps.2025.101057","DOIUrl":"10.1016/j.ajps.2025.101057","url":null,"abstract":"<div><div>Efficient reconstruction of severe cutaneous wounds necessitates the orchestration of effective cell-mediated matrix remodeling and robust protection against microbial invasion. Herein, we engineered a near-infrared light (NIR)-stimulated, thermo-responsive bilayer system based on a drug-loaded hydrogel with a thermal-responsive temperature of ∼42 °C as the matrix layer and an antibacterial nanofibrous mat as the top layer. The matrix layer integrates basic fibroblast growth factor (bFGF)-loaded thermosensitive gelatin (Gel) hydrogel with polydopamine-Cu²⁺ coated short nanofibers (P@SF). Upon NIR exposure, P@SF elicits a photothermal effect, causing a rapid increase in temperature by 13.4 °C within 1 min at a power density of 0.75 W/cm², which triggers the gel-sol transition of Gel and controls the release of bFGF. This, in turn, enhances fibroblast and endothelial cells ingrowth into the hydrogel, fostering cell functionalization and matrix remodeling. The top layer consists of poly(L-lactide-co-caprolactone) nanofibers functionalized with lysine-doped polydopamine and poly-<span>l</span>-lysine. It possesses antibacterial efficacy by isolating, controlling (76.23% for <em>E. coli</em> and 89.16% for <em>S. aureus</em>), and eliminating bacteria upon NIR activation. In rat skin wound models, this NIR-responsive smart bilayer system prevents <em>S. aureus</em>-mediated bacterial infection (indicative of reduced IL-6 expression), regulates CD31-positive neovascularization, and facilitates collagen remodeling for skin regeneration. In summary, this study introduces a novel strategy, inspired by the centralization of authority, for developing a smart thermo-responsive system with promising potential for the effective reconstruction of severe cutaneous wounds.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101057"},"PeriodicalIF":11.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724243","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":"Advances in plant-derived vesicle like nanoparticles-based therapies for inflammatory diseases","authors":"Zhifei Cheng ,&nbsp;Wengui Lu ,&nbsp;Wei Shao ,&nbsp;Chuan Zhang ,&nbsp;Yunfei She ,&nbsp;Rui Song ,&nbsp;Ruohan Qi ,&nbsp;Jiajia Song ,&nbsp;Wenjing Zhang ,&nbsp;Xiangwei Chang ,&nbsp;Ning Wang ,&nbsp;Qi Liu ,&nbsp;Shuangying Gui ,&nbsp;Qi Wang","doi":"10.1016/j.ajps.2025.101052","DOIUrl":"10.1016/j.ajps.2025.101052","url":null,"abstract":"<div><div>Dysregulated inflammatory reactions can result in detrimental effects to the body, thereby causing various diseases. Traditional treatments relying on anti-inflammatory drugs or nanoformulations often undermine the body's physiological immune functions or potentially exhibit biotoxicity. Extracellular vesicles, which contain a diverse array of anti-inflammatory substances and possess nanomedicine transport properties, are emerging as highly promising candidates for next-generation drug delivery systems and active biological agents. Plant-derived vesicle-like nanoparticles (PDVLNs) are nanostructured particles isolated from plants. Given their wide availability and low immunogenicity, PDVLNs are considered to hold great potential in the treatment of inflammatory diseases (IDs). In this review, we introduce the principle, design consideration and treatment mechanism associated with PDVLNs in treating various IDs. Specifically, the natural ingredients carried by PDVLNs not only help eliminate danger signals such as reactive oxygen species and reactive nitrogen species, but also hinder the initiation of inflammatory responses through various mechanisms. Moreover, engineered PDVLNs nanotechnology has been successfully employed in the treatment of IDs. Finally, the review discusses the current opportunities and challenges in this field and provides insights for the future clinical applications of PDVLNs in treating IDs.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101052"},"PeriodicalIF":11.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724245","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":"All-stage targeted therapy for invasive cryptococcosis through interaction between the secretory protein Cig1 and hemin","authors":"Liting Cheng ,&nbsp;Zhongyi Ma ,&nbsp;Xinlin Yang ,&nbsp;Xue Wang ,&nbsp;Yuqiong Wang ,&nbsp;Xinlong Liu ,&nbsp;Zhongjie Tang ,&nbsp;Dingxi Jang ,&nbsp;Guojian Liao ,&nbsp;Tongbao Liu ,&nbsp;Shuang Wu ,&nbsp;Chong Li","doi":"10.1016/j.ajps.2025.101053","DOIUrl":"10.1016/j.ajps.2025.101053","url":null,"abstract":"<div><div>Cryptococcosis, a serious systemic fungal infection caused by <em>Cryptococcus neoformans</em> (<em>C. neoformans</em>) and its variants, poses a significant clinical challenge due to its poor prognosis and severe health implications. The treatment of cryptococcal infections is complicated by several unique factors, stemming from both the pathogenic characteristics of the fungi and the biological barriers they exploit. These include the fungi's protective capsule, their ability to reside within host macrophages—thereby evading pharmacological intervention—and their involvement in multi-organ infections such as the lung and brain, in particular their strategic positioning within the brain, protected by the blood-brain barrier (BBB). To overcome these obstacles, precise active targeting emerges as a pivotal strategy. Identifying common targets is imperative to enhance therapeutic efficacy while ensuring the druggability of delivery systems. However, research on the methodology for selecting such shared targets remains sparse. In our investigation, we have pioneered the use of secreted proteins as shared target to trace the pathogens and their infection pathways. We identified the mannoprotein Cig1, prominently expressed on the surfaces of infected macrophages, lungs, and brains, as a viable shared target. On this basis, we utilized Hemin, a ligand for Cig1, to design liposomes (Hemin Lip) tailored for addressing complex fungal infections. By leveraging the interaction with the secreted protein Cig1, Hemin Lip specifically identifies and binds to organs and macrophages harboring cryptococcal infections, thereby facilitating targeted and efficacious clearance of both intracellular and extracellular fungus. Moreover, we have extended this targeting mechanism to other nanomedicinal platforms, including albumin nanoparticles. This study proposes an innovative drug delivery model that targets extracellular secretory proteins within the infection microenvironment, offering a streamlined formulation with the potential for effective therapy against complex infections.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 4","pages":"Article 101053"},"PeriodicalIF":11.9,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}