International Journal of Pharmaceutics: X最新文献

{"title":"PEGylated gold nanoparticles regulate metabolic flux in erythrocytes by inducing hemoglobin deoxygenation","authors":"Zeng He ,&nbsp;Wanjing Li ,&nbsp;Qin Zhao ,&nbsp;Doudou Hao ,&nbsp;Rui Zhong ,&nbsp;Hong Wang ,&nbsp;Xiaojie Zhang ,&nbsp;Libo Du ,&nbsp;Xiaodong Wu ,&nbsp;Jiaxin Liu","doi":"10.1016/j.ijpx.2026.100495","DOIUrl":"10.1016/j.ijpx.2026.100495","url":null,"abstract":"<div><div>Nanomedicines based on polyethylene glycol-functionalized gold nanoparticles (Au@PEG NPs) are usually administered by intravenous injection to improve bioavailability. It is widely accepted that surface modification with PEG can prevent direct interactions between AuNPs and proteins. Therefore, the interaction of Au@PEG NPs with plasma proteins and blood cells has not received enough attention. Our previous study demonstrated that Au@PEG NPs affect the oxygen-carrying capacity and deformability of erythrocytes through oxidative stress; however, the molecular mechanism of oxidative damage induced by Au@PEG NPs remains unclear. Due to the absence of cell organelles such as the nucleus and mitochondria in mature erythrocytes, we hypothesise that Au@PEG NPs primarily generate oxidative stress by interfere with metabolic flux in erythrocytes. We have employed dynamic light scattering (DLS), isothermal titration calorimetry (ITC) and surface plasmon resonance imaging (SPRi) to investigate the interaction between proteins and 30 nm Au@PEG NPs. ITC and SPRi data revealed that hemoglobin exhibits a higher affinity for 30 nm Au@PEG NPs compared to albumin (Ka: 1.46 × 10⁻⁴ <em>vs</em> 1.08 × 10⁻⁴ M⁻¹). Circular dichroism (CD) spectrum demonstrated a significant conformational shift in hemoglobin following incubation with 30 nm Au@PEG NPs, characterized by an increase in α-helix [(65.9 ± 0.6) % to (68.2 ± 0.6) %] and a decrease in β-sheet [(4.8 ± 0.3) % to (1.7 ± 0.2) %], which is consistent with its transition toward a deoxygenated state. By combining ICP-MS and four specific endocytosis inhibitors, we investigated the endocytic mechanism of Au@PEG NPs entering erythrocytes. The data revealed that the uptake efficiency of 30 nm Au@PEG NPs by erythrocytes was 68.2 ± 0.6 ng/10⁹ RBCs, with approximately 75% of the Au@PEG NPs were uptaked by erythrocytes through a mechanism involving caveolin- and clathrin-mediated endocytosis. Metabolomics and NADP⁺/NADPH analysis revealed that Au@PEG NPs induce hemoglobin deoxygenation, which in turn inhibits the pentose phosphate pathway and disrupts redox homeostasis, as reflected by the decrease of intracellular NADPH from 3.53 ± 0.50 nmol/10¹² RBCs to 2.67 ± 0.46 nmol/10¹² RBCs. However, tail vein injection of Au@PEG NPs did not impair the liver oxygen supply since mice can compensate for the hemoglobin deoxygenation effect of Au@PEG NPs by decreasing systolic blood pressure and increasing tissue perfusion. Our findings showed that Au@PEG NPs interfere with metabolic flux and generate oxidative stress in erythrocytes by changing the oxygenation state of hemoglobin, and these results suggest that future studies should pay more attention to hemocompatibility evaluations of nanomedicines before their clinical application.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100495"},"PeriodicalIF":6.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinspired and stimuli-responsive nanocomposites for targeted therapy in ovarian and endometrial tumors","authors":"Jihang Yao ,&nbsp;Lulu Liu ,&nbsp;Xiufei Teng ,&nbsp;Daming Chu ,&nbsp;Silu Ding ,&nbsp;Hui Li ,&nbsp;Hua Chang ,&nbsp;Jing Liu","doi":"10.1016/j.ijpx.2026.100493","DOIUrl":"10.1016/j.ijpx.2026.100493","url":null,"abstract":"<div><div>Ovarian and endometrial cancers pose significant therapeutic challenges due to late-stage diagnosis and resistance to traditional therapies. Recent progress in the development of multiscale, bioinspired, and stimuli-responsive nanocomposites presents promising avenues for targeted therapy. These nanocomposites, engineered across a range from micrometers to nanometers, utilize hierarchical structures to enhance drug delivery, reduce systemic toxicity, and improve therapeutic efficacy. Through the integration of nanoparticles, hydrogels, and polymeric nanocarriers, these materials can react to external stimuli such as pH, temperature, and magnetic fields, enabling precise and controlled release of therapeutic agents. This review examines the design principles of these sophisticated composites, concentrating on their capacity to replicate the tumor microenvironment and enhance targeting specificity in ovarian and endometrial cancers. Furthermore, it highlights current clinical obstacles, safety considerations, and the considerable potential of these materials in personalized gynecologic oncology, underscoring their efficacy at both macroscopic and nanoscopic levels.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100493"},"PeriodicalIF":6.4,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pH-responsive dual-drug nanoplatform for stromal remodeling and enhanced chemotherapy via MMP3/TGF-β inhibition","authors":"Tao Tan ,&nbsp;Yihan Wang ,&nbsp;Ran Cheng ,&nbsp;Dongsheng Yang","doi":"10.1016/j.ijpx.2026.100489","DOIUrl":"10.1016/j.ijpx.2026.100489","url":null,"abstract":"<div><div>The dense, fibrotic extracellular matrix (ECM) generated by cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) presents a formidable physical barrier that severely limits the penetration and efficacy of chemotherapeutic agents. This study aimed to design and validate a pH-responsive, dual-drug nanosystem (RPAE-QM) capable of overcoming this stromal resistance by coordinated delivery of a stromal-modulating agent and a potent cytotoxic payload. The RPAE-QM nanosystem was constructed to co-encapsulate the stromal-modulating agent quercetin (Que) and the chemotherapeutic drug DM1. RPAE-QM exhibited significant pH-responsive drug release, leading to strong synergistic cytotoxicity and superior tumor destruction capability in 3D spheroid models. Mechanistic investigation provided a definitive explanation for this efficacy. Molecular docking and molecular dynamics simulations predicted that Que. has high affinity and exceptional kinetic stability when binding to MMP-3. Subsequent experiments confirmed the downstream consequences of this interaction: treatment with Que. caused dose-dependent inhibition of both MMP-3 and TGF-<em>β</em>₁ secretion from CAFs. Moreover, this was accompanied by a significant, concentration-dependent reduction in the phosphorylation of Smad2/3, a key downstream effector of the TGF-<em>β</em> signaling pathway. The RPAE-QM nanosystem provides an effective dual-action strategy, simultaneously addressing the stromal barrier while delivering a potent cytotoxic agent. Mechanistically, our findings indicate that Que. suppresses the pro-fibrotic MMP3/TGF-<em>β</em>/Smad signaling axis in our CAF model. This work therefore introduces a dual-action therapeutic concept, offering a mechanistically-defined approach to disrupt stromal barriers and improve drug efficacy at the pre-clinical proof-of-concept stage.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100489"},"PeriodicalIF":6.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chitosan-based nanozyme hydrogels: Advanced antioxidant and sustained-release systems for the prevention and treatment of skin photoaging","authors":"Qucheng Huang ,&nbsp;Xiaojun Zhang ,&nbsp;YuanYuan Zuo ,&nbsp;Leiyi Wang ,&nbsp;Huan Sun ,&nbsp;Hewei Xu ,&nbsp;Miao Yu ,&nbsp;Chang Liu","doi":"10.1016/j.ijpx.2026.100491","DOIUrl":"10.1016/j.ijpx.2026.100491","url":null,"abstract":"<div><div>Photoaging of the skin is a chronic damage process caused by prolonged exposure to ultraviolet radiation, characterized by increased oxidative stress, activation of inflammatory responses, and collagen degradation. However, photoaging of the skin presents challenges in prevention, limited efficacy of therapeutic agents, and difficulties in repairing the damage. In recent years, chitosan-based hydrogels, which exhibit excellent biocompatibility, biodegradability, film-forming properties, and the ability to deliver sustained-release medication, have progressively emerged as cutting-edge therapeutic agents for treating photoaging of the skin. Nanozymes are nanomaterials possessing enzymatic functions that effectively scavenge reactive oxygen species generated by ultraviolet irradiation, exhibiting excellent antioxidant properties. Loading nanozymes into chitosan-based hydrogels not only combines the biocompatibility of chitosan hydrogels with the antioxidant properties of nanozymes to enhance therapeutic efficacy but also enables stable loading and controlled release of drugs and active ingredients. This further improves treatment efficiency while fully leveraging the moisturizing and restorative properties of the hydrogel matrix. This paper systematically summarizes the construction methods, performance optimization, and mechanism of action of chitosan-based nanozyme hydrogels in preventing and treating skin photoaging. It focuses on analyzing research advances in their capacity to scavenge free radicals, alleviate inflammation, and promote skin barrier repair, while exploring their application prospects and challenges in skin repair and the cosmetics sector.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100491"},"PeriodicalIF":6.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transferrin-modified multicomponent liposomes encapsulating paclitaxel-loaded β-elemene microemulsion enhance therapeutic efficacy in non-small-cell lung cancer","authors":"Yunyan Chen ,&nbsp;Ziwei Zhang ,&nbsp;Rui Xiong ,&nbsp;Yuqing Cao ,&nbsp;Qian Liu","doi":"10.1016/j.ijpx.2026.100488","DOIUrl":"10.1016/j.ijpx.2026.100488","url":null,"abstract":"<div><div>To achieve efficient accumulation and facilitate profound penetration of anti-tumor agents within neoplastic tissues stands as one of the most critical determinants influencing the efficacy of anticancer therapies. Herein, a multicomponent-based liposomes (Tf-PEM/L) by transferrin-modified encapsulating paclitaxel (PTX)-loaded <em>β</em>-elemene microemulsion (PEM) was fabricated, demonstrating significantly enhanced therapeutic efficacy against non-small cell lung cancer (NSCLC). Leveraging the synergistic mechanism of transferrin-mediated active targeting coupled with the enhanced permeability and retention (EPR) effect, Tf-PEM/L demonstrates a pronounced propensity for efficient and substantial accumulation at the tumor site. Following accumulation, the subsequently released PEM enables highly efficient deep penetration within tumor tissue, thereby achieving favorable anti-tumor therapeutic efficacy. Characterization of Tf-PEM/L revealed a mean particle size approximately (144.76 ± 9.34) nm, while the zeta potential exhibited a measurement of (−12.52 ± 0.28) mV. Notably, the transmission electron microscopy (TEM) images revealed the small-sized PEM were encapsulated within large-sized liposomes. In vitro cytotoxicity assays demonstrated that Tf-PEM/L elicited synergistic antitumor effects against A549 cells, underscoring its combinatorial therapeutic potential. In vivo studies, Tf-PEM/L demonstrated exceptional tumor-targeting capabilities as evidenced by quantitative biodistribution analyses. Moreover, Tf-PEM/L exhibited superior antitumor efficacy with tumor inhibition rate of (81.36 ± 3.87)% while markedly attenuating systemic toxicity, positioning it as a promising therapeutic strategy for NSCLC. Collectively, the Tf-PEM/L represents a promising targeted therapeutic strategy for NSCLC, with enhanced efficacy and safety profiles.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100488"},"PeriodicalIF":6.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of ultrasound and ultrasound-responsive materials in wounds: A systematic review","authors":"Jialei Luo ,&nbsp;Liwan Song ,&nbsp;Xinyi Yan ,&nbsp;Xiaolu Ma ,&nbsp;Jianqing Gao ,&nbsp;Ying Luo ,&nbsp;Gaoyi Yang","doi":"10.1016/j.ijpx.2026.100485","DOIUrl":"10.1016/j.ijpx.2026.100485","url":null,"abstract":"<div><div>Wound healing is a multifaceted biological process that is highly susceptible to disruption by numerous internal and external factors, resulting in delayed tissue repair. Recent advancements have highlighted the therapeutic potential of ultrasound, especially when integrated with emerging smart materials, which together offer promising strategies for enhancing wound care outcomes. Low- and high-intensity ultrasound (US) use mechanisms such as cavitation, acoustic streaming, and radiation forces to disrupt biofilms, improve drug permeability, and promote tissue regeneration. When combined with US-responsive materials, such as scaffolds, piezoelectric composites, microbubbles, microneedles, and flexible patches, these systems enable targeted functions, including controlled drug release, antimicrobial activity, and enhanced deep tissue penetration. These responsive materials effectively overcome the limitations of conventional wound dressings, which often suffer from poor drug bioavailability, susceptibility to infection, and a lack of personalized therapeutic capabilities. This review systematically explores 5 categories of advanced materials, with a focus on their synergistic interactions with ultrasound to enhance wound healing outcomes. By elucidating the interactions between material-US and their translational implications, this review offers new perspectives to advance the clinical development of precision-based, next-generation wound therapies.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100485"},"PeriodicalIF":6.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HPMA polymers as functional excipients in dermal nanoformulations of imiquimod","authors":"Eliška Kurfiřtová ,&nbsp;Stanislav Chvíla ,&nbsp;Nikola Strnádková ,&nbsp;Vendula Janoušková ,&nbsp;Petr Chytil ,&nbsp;Tomáš Etrych ,&nbsp;Jarmila Zbytovská","doi":"10.1016/j.ijpx.2026.100486","DOIUrl":"10.1016/j.ijpx.2026.100486","url":null,"abstract":"<div><div>A key challenge in topical drug delivery is the inherently low bioavailability of many active compounds within skin tissue. Here, we present the first comprehensive study investigating the impact of biocompatible hydrophilic polymers based on <em>N</em>-(2-hydroxypropyl)methacrylamide (p(HPMA)) on skin barrier properties and its potential to enhance drug permeation. Using imiquimod (IMQ), a model compound known for its poor dermal delivery, we demonstrate that p(HPMA) can significantly influence transport across the skin. To enhance the dermal delivery of IMQ, we investigated three p(HPMA) polymers of varying molecular sizes (5, 20, 80 kg/mol) with very low dispersity. Our initial focus was on the p(HPMA) interaction with the skin barrier, specifically within the <em>stratum corneum</em> (SC), which was studied by confocal microscopy. Results revealed that p(HPMA) can penetrate into deeper skin layers, with this ability inversely correlated with their molecular weight. FTIR analysis confirmed that the polymers increase SC hydration without disrupting lipid organization. As demonstrated by the <em>ex vivo</em> skin permeation study, the smallest p(HPMA) polymer (5 kg/mol) produced the strongest enhancement effect on IMQ delivery into skin tissue. Relative to p(HPMA)-free controls, IMQ accumulation increased by 90% from the conventional suspension and by 10% and 50% from the nanoemulsion and nanocrystal formulations, respectively. These findings substantiate the role of p(HPMA) as an effective skin-penetration enhancer and support its further investigation for optimizing topical drug-delivery systems.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100486"},"PeriodicalIF":6.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 lipid nanoparticles for cancer vaccine delivery: Challenges and future perspectives","authors":"Nurhasni Hasan ,&nbsp;Maryam Aftab ,&nbsp;Sania Ikram ,&nbsp;Apon Zaenal Mustofa ,&nbsp;Sriwidodo Sriwidodo ,&nbsp;Huda Shalahudin Darusman ,&nbsp;Muhammad Nur Amir ,&nbsp;Theofilus A. Tockary ,&nbsp;Satoshi Uchida","doi":"10.1016/j.ijpx.2026.100484","DOIUrl":"10.1016/j.ijpx.2026.100484","url":null,"abstract":"<div><div>Cancer remains a major global health burden, with 19.3 million new cases and 10.3 million deaths reported in 2020. Conventional modalities such as surgery, radiotherapy, and chemotherapy often fail to prevent metastasis or recurrence. Cancer vaccination, which mobilizes durable, tumor-specific immunity, has gained traction, and LNPs have become pivotal to this approach. Originally optimized for siRNA, LNPs’ core–shell architecture protects nucleic acids, enhances cellular uptake, and enables efficient cytosolic delivery. Their clinical validation in infectious-disease messenger RNA (mRNA) vaccines has catalyzed rapid progress toward oncology applications. Preclinical and early-phase trials have indicated that mRNA-LNPs encoding tumor-associated antigens or patient-specific neoantigens can expand cytotoxic T cells and elicit preliminary antitumor activity. Key barriers remain. Manufacturing cost and batch consistency challenge scale-up. Physicochemical instability necessitates cold-chain logistics and complicates global deployment. Reactogenicity and anti-PEG antibodies increase safety and dosing concerns. Within tumors, immunosuppressive microenvironments, heterogeneous antigen expression, and suboptimal lymphoid targeting limit the efficacy of vaccines. This review describes the advances in LNP design (ionizable and biodegradable lipids, PEG alternatives, ligand-mediated targeting), formulation strategies (thermostable and lyophilized systems), and delivery routes (intranodal and intratumoral) to overcome these bottlenecks. It also highlights synergistic combinations with checkpoint blockade, radiotherapy, and innate agonists, and examines emerging pipelines leveraging AI-guided neoantigen discovery and quality control. By integrating material engineering, immunology, and translational evidence, we identified failure points and proposed a roadmap for next-generation LNP-based cancer vaccines. The goal is to accelerate progress from bench to clinic, while improving manufacturability, access, and durable patient benefits.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100484"},"PeriodicalIF":6.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligand-modified liposomes as drug delivery systems for the active targeting of pancreatic cancer","authors":"Yerin Jang ,&nbsp;Jaehee Jang ,&nbsp;Jaewoo Son ,&nbsp;Hee-Young Lee ,&nbsp;Jonghoon Choi","doi":"10.1016/j.ijpx.2026.100483","DOIUrl":"10.1016/j.ijpx.2026.100483","url":null,"abstract":"<div><div>Pancreatic cancer is among the most fatal malignancies worldwide. The aggressive nature of this disease, coupled with late-stage diagnosis and limited therapeutic options, highlights the urgent need for innovative treatment approaches. Targeted therapy has emerged as a promising strategy to enhance therapeutic efficacy while minimizing systemic toxicity. Liposomes, as versatile nanoparticles, have shown significant potential to contribute to the develpment of drug delivery system. These lipid-based vesicles encapsulate chemotherapeutic drugs, shield them from degradation, and promote greater accumulation within tumor cites. Furthermore, liposomes can be surface-modifed with various ligands to improve their specificity and cellular uptake. Research on liposome-based targeted chemotherapy for pancreatic cancer has explored useful ligand-based strategies to enhance drug delivery to pancreatic cancer cells. In this review, liposome-based targeted strategies for pancreatic cancer are classified by ligand type, including antibodies, aptamers, carbohydrates, proteins and peptides, and integrates case studies to demonstrate how different targeting approaches translate into improved cellular uptake, therapeutic efficacy, and antitumor effects. In addition, emerging formulations such as dual-targeting liposomes are described, highlighting their potential to further strengthen treatment performance. The review summarizes the current research landscape of liposome-based targeted drug delivery systems for pancreatic cancer, providing insights into promising biomarkers and ligand-mediated targeting strategies. It further discusses broader opportunities for target exploration and liposomal design optimization, as well as future research directions aimed at overcoming existing limitations and improving therapeutic outcomes.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100483"},"PeriodicalIF":6.4,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering exosomes for cancer therapy - Modification technologies and subcellular targeting strategies: A review","authors":"Fengbo Liu,&nbsp;Chengxing Xia,&nbsp;Hang Yu,&nbsp;Xiaofang Yang,&nbsp;Liping Ge,&nbsp;Chunwei Ye","doi":"10.1016/j.ijpx.2025.100473","DOIUrl":"10.1016/j.ijpx.2025.100473","url":null,"abstract":"<div><div>Exosomes are secreted lipid bilayer vesicles of 30–150 nm in diameter. Their low immunogenicity, excellent biocompatibility, and inherent targeting capability make them a promising drug delivery vehicle for cancer therapeutics. However, the use of natural exosomes is still challenging for therapeutic applications, including limited targeting precision and drug-loading efficiency, necessitating engineered modification strategies to optimize their performance. To further enhance exosome targeting capacity, recent studies have explored precision delivery strategies targeting subcellular structures such as lysosomes, nuclei, mitochondria, and the endoplasmic reticulum, thereby improving exosome therapeutic potential. This review systematically summarizes the core advantages of exosomes as drug carriers, elaborates on their engineering modification methods, and highlights recent advances in strategies to improve exosomes targeting of subcellular structures to enhance antitumor efficacy. The review aims to provide a theoretical foundation and technical guidance for developing exosome-based precision therapies for cancer.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100473"},"PeriodicalIF":6.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}