Asian Journal of Pharmaceutical Sciences最新文献

{"title":"Bioengineered milk-derived extracellular vesicles implementing high drug loading and membrane integrity for efficient oral drug delivery","authors":"Mingjie Ni,&nbsp;Liyun Xing,&nbsp;Yating Wang,&nbsp;Xi Liu,&nbsp;Lie Zhang,&nbsp;Yuting Li,&nbsp;Lian Li,&nbsp;Yuan Huang","doi":"10.1016/j.ajps.2025.101093","DOIUrl":"10.1016/j.ajps.2025.101093","url":null,"abstract":"<div><div>Milk-derived extracellular vesicles (EVs) are promising for oral drug delivery, yet different loading methods exhibit distinct impacts on drug encapsulation and membrane integrity. This study demonstrated that sonication method achieved high drug encapsulation in commercial milk-derived EVs (S-CM EVs), but impaired EV structure, compromising transcytosis. Incubation method (I-CM EVs) preserved EVs delivery ability, but had low drug loading. Further proteomic and transmembrane studies showed that sonication greatly damaged membrane proteins involved in trans-epithelial transportation, especially endoplasmic reticulum-Golgi pathway. To overcome this dilemma, we generated a hybrid CM EVs (H<img>CM EVs) by fusing I-CM EVs and S-CM EVs. H<img>CM EVs demonstrated comparable drug encapsulation to S-CM EVs (56.14 %), significantly higher than I-CM EVs (11.92 %). Importantly, H<img>CM EVs could maintain efficient drug delivery capability by restoring membrane fluidity, repairing damaged proteins, and enhancing enzyme resistance of S-CM EVs. H<img>CM EVs exhibited excellent absorption characteristics with 1.85-fold higher of area under the curve and 2.50-fold higher of max plasma concentration than those of S-CM EVs. On type Ⅰ diabetic mice, orally delivery of insulin loaded H<img>CM EVs and I-CM EVs showed improved hypoglycemic effects with pharmacological availabilities of 5.15 % and 5.31 %, which was 1.7-fold higher than that of S-CM EVs (3.00 %). This H<img>CM EVs platform not only achieved high drug loading and maintained functionality for effective oral delivery but also highlighted the significant translational potential for improved clinical outcomes.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 5","pages":"Article 101093"},"PeriodicalIF":11.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145325246","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":"Stealth hemostatic anchors with VWF-driven navigation and plasmin-triggered tranexamic release for hematoma containment in cerebral hemorrhage","authors":"Yu-E Wang ,&nbsp;Haoqi Wang ,&nbsp;Shanshan Han ,&nbsp;Dong Cen ,&nbsp;Zibin Zhang ,&nbsp;Ke Xiao ,&nbsp;Likun Wang ,&nbsp;Xingjie Wu ,&nbsp;Qianqian Guo ,&nbsp;Ling Tao ,&nbsp;Wei Li ,&nbsp;Xiangchun Shen ,&nbsp;Guofeng Wu","doi":"10.1016/j.ajps.2025.101091","DOIUrl":"10.1016/j.ajps.2025.101091","url":null,"abstract":"<div><div>The high mortality and disability rates associated with spontaneous intracerebral hemorrhage (sICH) are primarily attributed to secondary injuries caused by hematoma expansion from continuous bleeding or rehemorrhage. Rapid hemostasis to prevent hematoma progression is critical in clinical emergencies for improving surgical outcomes and patient prognosis. For internal hemorrhages inaccessible to external interventions, especially for sICH, intravenous hemostatic strategies are essential regardless of ultimate surgical eligibility. This study reported a stealth hemostatic anchor system based on peptide-drug conjugates. Tranexamic acid (TXA), a clinically approved antifibrinolytic agent, served as the hemostatic component, while a Von Willebrand factor-binding peptide (VBP) enabled targeted delivery by specifically binding to von Willebrand factor exposed at vascular injury sites. A plasmin-cleavable linker was incorporated to control TXA release, ensuring site-specific drug activation. The plasmin-responsive peptide-drug conjugate (RPDC) was synthesized by covalently linking TXA to VBP via the plasmin-cleavable linker. <em>In vitro</em> and <em>in vivo</em> experiments verified the targeted hemostatic efficacy of RPDC, especially demonstrating 42 % reduction in hematoma volume (<em>P</em> &lt; 0.001 vs. saline; <em>P</em> &lt; 0.05 vs. free TXA) with mitigated peri‑hematomal pathology in the collagenase-induced ICR mouse ICH model. These results highlight the potential of the stealth hemostatic anchor as a precision therapeutic strategy for managing sICH, particularly in cases of internal hemorrhages inaccessible to surgical intervention or visual inspection. The plasmin-dependent targeting mechanism enables precise drug localization at cryptic hemorrhage sites, but further studies in larger animal models are needed to confirm its efficacy. This design offers a theoretical framework for advancing emergency interventions in cerebral hemorrhage and addressing challenges related to inaccessible bleeding sites.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 5","pages":"Article 101091"},"PeriodicalIF":11.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145325247","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":"Macrophage-centered therapy strategies: A promising weapon in cancer immunotherapy","authors":"Simiao Wang ,&nbsp;Jiayi Liu ,&nbsp;Yaxin Cui ,&nbsp;Man Sun ,&nbsp;Wei Wang ,&nbsp;Jiayi Chen ,&nbsp;Jingkai Gu ,&nbsp;Zhaogang Yang","doi":"10.1016/j.ajps.2025.101063","DOIUrl":"10.1016/j.ajps.2025.101063","url":null,"abstract":"<div><div>Macrophages are critical phagocytes in the immune system, and tumor-infiltrating macrophages can substantially influence the efficacy and prognosis of immunotherapy. Therefore, macrophages may serve as therapeutic targets for modulating the tumor immune microenvironment. Macrophage-based drug delivery systems have been extensively evaluated owing to their excellent biocompatibility, long half-life, and inherent ability to migrate and accumulate at sites of inflammation, such as tumors. Live macrophages and their membrane coatings contain abundant receptor proteins that facilitate payload transport across physiological barriers. In this review, we discuss strategies that utilize macrophages as targets and delivery carriers for cancer immunotherapy. Here, we summarize the different macrophage phenotypes, tumor-associated macrophage-targeting strategies, and biomimetic delivery carriers derived from macrophages used in immunotherapy. Overall, macrophage-centered strategies for cancer therapy hold considerable promise for clinical applications.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 5","pages":"Article 101063"},"PeriodicalIF":11.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145325410","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":"Metal-organic frameworks as therapeutic chameleons: revolutionizing the cancer therapy employing novel nanoarchitectonics","authors":"Sajja Bhanu Prasad ,&nbsp;Akshay Shinde ,&nbsp;Dadi A. Srinivasrao ,&nbsp;Paras Famta ,&nbsp;Saurabh Shah ,&nbsp;Tejaswini Kolipaka ,&nbsp;Giriraj Pandey ,&nbsp;Deelip Gaonker ,&nbsp;Ganesh Vambhurkar ,&nbsp;Pooja Khairnar ,&nbsp;Rahul Kumar ,&nbsp;Amol G. Dikundwar ,&nbsp;Vinaykumar Kanchupalli ,&nbsp;Saurabh Srivastava","doi":"10.1016/j.ajps.2025.101054","DOIUrl":"10.1016/j.ajps.2025.101054","url":null,"abstract":"<div><div>Cancer is one of the most complex diseases and the second leading cause of mortality worldwide. Due to its poor prognosis and challenges in diagnosis, eradicating cancer remains highly difficult. The limitations associated with conventional therapies have led to the emergence of copious therapeutic strategies such as chemotherapy, phototherapy, starvation therapy, radiotherapy and immunotherapy; however, limited therapeutic efficacy, poor tumor cell selectivity and substantial adverse effects remain significant concern. Attributed to the expeditious advancement of nanotechnology, the amalgamation of nanomaterials with therapeutic approaches provides an opportunity to address the shortcomings of conventional chemotherapy. Metal-organic frameworks (MOFs), which consist of bridging ligands and ions/clusters connected by coordination bonds, have been widely used in cancer therapy to address the limitations of currently therapeutic interventions, such as poor efficacy, low stability and severe side effects. This potential arises from their tuneable porosities, high specific surface area-to-volume ratio, tailorable diameters, tractable morphologies, variegated compositions, biocompatibility and facile functionalization. We summarized the role of MOF-based nanoplatforms along with mechanistic insights into emerging avenues—such as cuproptosis, ferroptosis, cell-penetrating and biomimetic MOFs, and tumor microenvironment-responsive MOFs— alongside recent advancements in mono- and multifunctional cancer therapeutics. Theragnostic and imaging functionalities, as well as regulatory considerations and future prospects of MOF-based nanoplatforms utilized in cancer treatment, are also discussed.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 5","pages":"Article 101054"},"PeriodicalIF":11.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145325409","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":"Overcoming corneal barriers: Posaconazole loaded cationic surfactant vesicles for enhanced ocular permeability and anti-fungal efficacy","authors":"Kshitija M. Phatak ,&nbsp;Ankita N. Yawalkar ,&nbsp;Sushant S. Sole ,&nbsp;Pradeep R. Vavia","doi":"10.1016/j.ajps.2025.101087","DOIUrl":"10.1016/j.ajps.2025.101087","url":null,"abstract":"<div><div>Posaconazole (PCZ) is a broad-spectrum anti-fungal drug approved by FDA and currently used off-label for the treatment of fungal keratitis (FK). Although ocular route serves as the most bioavailable route for treating FK, delivery of PCZ to the eye remains a challenge due to poor permeation though the cornea and rapid elimination from the eye. Here we outline a comprehensive formulation development process, beginning with <em>in silico</em> studies, progressing through <em>in vitro</em> evaluations, and ultimately achieving therapeutic benefits <em>in vivo</em>. We report modified niosome-like surfactant vesicles, hereafter termed as NioTherms, formulated using a novel and simple heat-mix method, encapsulating PCZ for ocular administration in the form of an <em>in situ</em> gel. Excipient screening performed using <em>in silico</em> simulations highly correlate with <em>in vitro</em> studies (R²=0.77), guiding optimization by Quality by Design (QbD) approach for encapsulating PCZ in NioTherms resulting in particles with an average size of 180.7 ± 2.3 nm, zeta potential of +27.5 ± 2.2 mV and entrapment efficiency of 87.6 % ± 1.7 %. A 2-fold increase in both mucin binding and cellular uptake indicates a functional role of positive surface charge in enhancing mucoadhesive properties of PCZ-NioTherms. In an <em>in vivo</em> murine ocular keratitis model, we demonstrate a 2-fold enhancement in trans-corneal permeability of PCZ-NioTherms and a 3-fold reduction in fungal burden compared to the control standard of care, the PCZ solution. Owing to a facile formulation process, we anticipate that PCZ-NioTherms would serve as a clinically translatable and patient compliant therapeutic intervention for treating FK.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 5","pages":"Article 101087"},"PeriodicalIF":11.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145263503","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":"2025-08-01","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":"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":"2025-08-01","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":"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":"2025-08-01","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":"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":"2025-08-01","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":"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":"2025-08-01","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}