Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-06-18DOI: 10.1080/10717544.2025.2519470
Yilin Xu, Min Wang, Jing Wu, Manshu Zou, Donghai Wu, Jing Gong, Pingjie Wang, Hong Yan, Xinhua Xia
{"title":"Targeted treatment of hepatocellular carcinoma with aptamer-guided solid lipid nanoparticles loaded with norcantharidin.","authors":"Yilin Xu, Min Wang, Jing Wu, Manshu Zou, Donghai Wu, Jing Gong, Pingjie Wang, Hong Yan, Xinhua Xia","doi":"10.1080/10717544.2025.2519470","DOIUrl":"10.1080/10717544.2025.2519470","url":null,"abstract":"<p><p>Liver cancer is a common malignancy in the world, and its incidence and mortality rate are increasing year by year. The disease has a short course and a high mortality rate, posing a serious threat to humanity and health. The objective of this study is to create novel liver-targeted nanoparticles as a potential treatment for liver cancer. The aptamer (APS613-1) modified redox-sensitive norcantharidin solid lipid nanoparticles (Apt-PEG<sub>2000</sub>-ss-NCTD-SLNs) were prepared by emulsified ultrasonic dispersion method and characterized. The tumor targeting, antitumor effect and safety of the nanoparticles were investigated and evaluated <i>in vitro</i> and <i>in vivo</i>. The particle size of Apt-PEG<sub>2000</sub>-ss-NCTD-SLNs was 87.95 ± 3.32 nm, and the encapsulation efficiency was about 80.74 ± 2.36%, which had good biocompatibility. The results of <i>in vitro</i> experiments showed that, compared with unmodified solid lipid nanoparticles (NCTD-SLNs), Apt-PEG<sub>2000-</sub>ss-NCTD-SLNs had better targeting for liver tumor cells, and a stronger ability to inhibit cell proliferation and migration, as well as promote cell apoptosis. The <i>in vivo</i> results revealed that Apt-PEG<sub>2000</sub>-ss-NCTD-SLNs demonstrated good safety and anti-tumor efficacy, and its mechanism was achieved through the inhibition of cell proliferation and induction of apoptosis. The functionalized nanoparticles modified by aptamer APS613-1 can be used for the liver-targeted delivery of antitumor drugs for the treatment of liver cancer, and Apt-PEG<sub>2000</sub>-ss-NCTD-SLN is a potential drug for the treatment of liver cancer.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2519470"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-10-05DOI: 10.1080/10717544.2025.2565480
Liju Jiang, Ziyu Fu, Baibai Ye, Xuanye Feng, Zhen Chen, Qing Chen, Yuanxiong Long, Shengmei Wang, Guiming Deng
{"title":"Metal nanoparticles in cancer theranostics: from synthesis to tumor microenvironment-responsive applications.","authors":"Liju Jiang, Ziyu Fu, Baibai Ye, Xuanye Feng, Zhen Chen, Qing Chen, Yuanxiong Long, Shengmei Wang, Guiming Deng","doi":"10.1080/10717544.2025.2565480","DOIUrl":"https://doi.org/10.1080/10717544.2025.2565480","url":null,"abstract":"<p><p>Cancer poses a major threat to human health, and conventional treatments (such as surgery, radiotherapy (RT), and chemotherapy) are often associated with significant toxic side effects, poor targeting, and drug resistance. In recent years, nanomedicine, an emerging interdisciplinary field, has provided novel strategies for cancer diagnosis and therapy by enabling precise drug delivery and multifunctional integration. Among various nanoplatforms, metal nanoparticles (MNPs) have become a research hotspot due to their unique physicochemical properties, including optical characteristics, catalytic activity, and surface modifiability. This article systematically explores the role of MNPs in cancer therapy. It first outlines their classification and synthesis strategies. Subsequently, it analyzes their innovative applications in tumor diagnosis, RT, chemotherapy, and immunotherapy. A key focus is placed on elucidating how MNPs exploit distinctive features of the tumor microenvironment - such as acidic pH, elevated reactive oxygen species (ROS) levels, and high glutathione (GSH) concentrations - to achieve responsive and targeted drug delivery. Finally, the main challenges currently faced in this field are analyzed. This review aims to provide theoretical guidance and technical references for the rational design and clinical translation of MNPs.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2565480"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231684","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":"Ionic liquid-iontophoresis mediates transdermal delivery of sparingly soluble drugs.","authors":"Wenyan Gao, Wenmin Xing, Zhan Tang, Qiao Wang, Wenying Yu, Qi Zhang","doi":"10.1080/10717544.2025.2489730","DOIUrl":"https://doi.org/10.1080/10717544.2025.2489730","url":null,"abstract":"<p><p>Low solubility restricted transdermal penetration of drugs. We aimed to develop a novel ionic liquid-iontophoresis (IL-IS) technology and assess their efficacy and primary factors in facilitating transdermal drug delivery. Five choline-based ILs with different chain length were synthesized and validated, and the impact of IL and/or IS technology on transdermal penetration of model drugs were investigated. The results indicated that five groups of ILs synthesized in this study exhibited minimal level of toxicity, and the longer the chain of acid ligands of ILs, the greater the cytotoxicity. The longer chain of acid ligand was demonstrated superior solubilizing capabilities compared to the shorter chain. Cinnamic acid-choline-based IL ([Cho] [Cin]) significantly improved permeation of all three model drugs, and permeation quantity was linearly positively associated with the concentration of ILs. The 10 h cumulative permeation of aripiprazole applied with ILs alone was enhanced by about 14-fold when paired with IS, and the penetration was linearly positively associated with the concentration and current strength of the ILs. <i>In vivo</i> results indicated that IL and/or IS technology primarily facilitated drug penetration into the skin, with potential involvement of endocytosis in this process. This study demonstrated that [Cho] [Cin] exhibited a significant enhancement in the transdermal delivery of three sparingly soluble drugs. It further enhanced the transdermal permeation of weak base drug following with the combining IL and IS technology. These findings highlighted that the IL-IS technology holded promise for facilitating the transdermal delivery of sparingly soluble and weak base drugs.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2489730"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-06-12DOI: 10.1080/10717544.2025.2509969
Ryouken Kimura, Tomoyoshi Yamano, Uryo Onishi, Xiabing Lyu, Kanto Nagamori, Toan Van Le, Mitsutoshi Nakada, Rikinari Hanayama
{"title":"Selective expansion and differentiation of antigen-specific CD4<sup>+</sup> T-helper cells by engineered extracellular vesicles.","authors":"Ryouken Kimura, Tomoyoshi Yamano, Uryo Onishi, Xiabing Lyu, Kanto Nagamori, Toan Van Le, Mitsutoshi Nakada, Rikinari Hanayama","doi":"10.1080/10717544.2025.2509969","DOIUrl":"10.1080/10717544.2025.2509969","url":null,"abstract":"<p><p>Extracellular vesicles (EVs), particularly small EVs (sEVs), are lipid bilayer vesicles secreted by various cell types and play a key role in intercellular communication. These vesicles are promising tools for cancer immunotherapy owing to their biocompatibility, low immunogenicity, and capacity for targeted drug delivery. In this study, we aimed to assess the potential of engineered antigen-presenting EVs (AP-EVs) to selectively expand and differentiate antigen-specific CD4<sup>+</sup> T cells. We engineered two types of AP-EVs: AP-EVs-Th1 expressing MHC class II, CD80, and interleukin (IL)-12 on their surface to promote Th1 differentiation, and AP-EVs-Th2 expressing MHC class II, CD80, and IL-4 to induce Th2 differentiation. <i>In vitro</i> experiments demonstrated that AP-EVs successfully induced the antigen-specific proliferation and differentiation of Th1 and Th2 cells, respectively. Notably, <i>in vivo</i> administration of AP-EVs-Th1 significantly enhanced the proliferation and differentiation of tumor antigen-specific Th1 cells, leading to robust anti-tumor effects in a murine melanoma model. These findings highlight the potential of AP-EVs-Th1 for cancer immunotherapy, particularly in augmenting CD4<sup>+</sup> T cell responses. Furthermore, the versatility and adaptability of EV-based therapies make them beneficial for the development of personalized immunotherapeutic strategies for various cancer types, offering the advantages of targeted immune modulation, ease of use, and reduced risk compared to cell-based therapies.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2509969"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-07-29DOI: 10.1080/10717544.2025.2537818
Mehul Desai, Beth Faiman, Lisa A Gorski, Ashley Miles, Valentina Sterlin, Nicole Curry
{"title":"Letter to the Editor regarding 'Evaluating nurse preferences for a novel on-body delivery system vs. manual syringes for large-volume subcutaneous drug administration: a survey study'.","authors":"Mehul Desai, Beth Faiman, Lisa A Gorski, Ashley Miles, Valentina Sterlin, Nicole Curry","doi":"10.1080/10717544.2025.2537818","DOIUrl":"10.1080/10717544.2025.2537818","url":null,"abstract":"","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2537818"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-05-29DOI: 10.1080/10717544.2025.2509962
Xiao-Yun Hou, Xiao-Ling Zhang, An-Kang Ying, Yu-Xin Yue, Tao Yang, Dong-Sheng Guo, Zhi-Qing Li
{"title":"Ophthalmic formulation of methotrexate: a strategy of using the self-assembled LacAC4A nanoparticles for non-invasive drug delivery to the ocular posterior segment.","authors":"Xiao-Yun Hou, Xiao-Ling Zhang, An-Kang Ying, Yu-Xin Yue, Tao Yang, Dong-Sheng Guo, Zhi-Qing Li","doi":"10.1080/10717544.2025.2509962","DOIUrl":"10.1080/10717544.2025.2509962","url":null,"abstract":"<p><p>Drug delivery to ocular posterior segment remains difficult due to the challenges imposed by dynamic and static ocular barriers, lesion point targeting, and off-target effect. In this study, a novel approach is demonstrated for non-invasive drug delivery to the ocular posterior segments using lactose-modified azocalix[4] arene (LacAC4A) as a supramolecular ocular drug delivery platform. LacAC4A contains azo groups and is covalently modified by lactose groups, which confers active targeting to the retina, and induces a hypoxic response. The immunomodulator methotrexate (MTX), which is commonly used in ophthalmology to treat immune system diseases such as uveitis, was also selected as a guest to prepare MTX@LacAC4A. The prepared LacAC4A and MTX@LacAC4A systems were characterized, then the internalization mechanisms and hypoxia response abilities were determined through flow cytometry and fluorescence imaging, respectively. Besides, the delivery route and efficiency were verified, and the safety profile of MTX@LacAC4A was evaluated in multiple dimensions. Importantly, it was found that the prepared MTX@LacAC4A exhibits good biocompatibility, can effectively reach the posterior segment, and demonstrates potential ophthalmic applications. These findings lay the grounds for the future development of non-invasive ocular posterior segment disease treatments based on the advanced use of LacAC4A as a drug delivery platform.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2509962"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-05-29DOI: 10.1080/10717544.2025.2509973
Ravi Parashar, Preeti K Suresh
{"title":"Emerging liposomal therapies for diabetic retinopathy: a review of novel targeting approaches and advances in retinal health outcomes.","authors":"Ravi Parashar, Preeti K Suresh","doi":"10.1080/10717544.2025.2509973","DOIUrl":"10.1080/10717544.2025.2509973","url":null,"abstract":"<p><p>Diabetic retinopathy (DR), which affects over millions of individuals globally, is the leading cause of permanent visual loss. Current therapies, including as intravitreal anti-vascular endothelial growth factor (VEGF) medications and laser photocoagulation, are limited by frequent dosing and side effects. Liposomes, with their ability to encapsulate hydrophilic and hydrophobic medications, offer tailored delivery, prolonged release, and low systemic toxicity. This study looks at advances in liposomal formulations that address DR's multifactorial etiology, including as anti-angiogenic, anti-inflammatory, and antioxidant processes. We assess new preparation methods (e.g. supercritical CO<sub>2</sub>, microfluidics) and clinical considerations, including stability and cost-effectiveness. To address the heterogeneity of DR, future endeavors will prioritize combinatorial medications and customized therapy.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2509973"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhalable nanoparticle-based delivery systems for the treatment of pulmonary infections: <i>Status quo</i> and barrier-overcoming strategies.","authors":"Yihong Gao, Wenhao Wang, Xiao Yue, Guanlin Wang, Kaiqing Zhang, Chuanbin Wu, Ziyu Zhao, Zhengwei Huang, Xuejuan Zhang","doi":"10.1080/10717544.2025.2544683","DOIUrl":"10.1080/10717544.2025.2544683","url":null,"abstract":"<p><p>Pulmonary infection is a serious public health challenge with high morbidity and mortality. The employment of antibiotics is the first-line treatment for pulmonary infections, while other novel anti-infection agents, such as antimicrobial peptides, have also been developed due to the emergence of drug resistance. Recently, inhalable nanoparticle-based delivery systems have garnered significant attention for the delivery of anti-infection agents, which possess great advantages like high lung accumulations and precise delivery performances. However, the respiratory physiological structure, mucus and biofilm have been considered as the barriers that nanoparticle drug delivery systems facing, which compromise the therapeutic effects. In this integrative review, recent advances in the inhalable nanoparticle-based delivery system were introduced. In addition, we focused on the biological characteristics of these barriers and discussed effective strategies to overcome the obstacles, including precise deposition in the lower respiratory tract infection site, effective penetration of mucus and breaking of the biofilm barrier. To sum up, this review aimed to deepen the understanding of the fate of anti-infective nanoformulations in pulmonary delivery and find effective strategies to address the barriers, thus providing new insights for the development of pulmonary delivery systems against pulmonary infections.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2544683"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-04-23DOI: 10.1080/10717544.2025.2494775
Dmitri Simberg, Yechezkel Barenholz, Steve R Roffler, Katharina Landfester, Alexander V Kabanov, Seyed M Moghimi
{"title":"PEGylation technology: addressing concerns, moving forward.","authors":"Dmitri Simberg, Yechezkel Barenholz, Steve R Roffler, Katharina Landfester, Alexander V Kabanov, Seyed M Moghimi","doi":"10.1080/10717544.2025.2494775","DOIUrl":"10.1080/10717544.2025.2494775","url":null,"abstract":"<p><p>PEGylation technology, that is grafting of poly(ethylene glycol)(PEG) to biologics, vaccines and nanopharmaceuticals, has become a cornerstone of modern medicines with over thirty products used in the clinic. PEGylation of therapeutic proteins, nucleic acids and nanopharmaceuticals improves their stability, pharmacokinetic and biodistribution. While PEGylated medicines are safe in the majority of patients, there are growing concerns about the emergence of anti-PEG antibodies and their impact on the therapeutic efficacy of PEGylated medicines as well as broader immune responses, particularly in complement activation and hypersensitivity reactions. These concerns are beginning to scrutinize the future viability of PEGylation technology in medicine design. Here, we outline these concerns, encourage more efforts into looking for comprehensive scientific evidence on the role of anti-PEG antibodies in hypersensitivity reactions, discuss alternatives to PEG and propose strategies for moving PEGylation technology forward.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2494775"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sequential nanotheranostics based on hollow mesoporous silica loaded doxorubicin and seed kernel extract from <i>Mangifera indica</i> L. as adjuvant therapy against hepatocellular carcinoma.","authors":"Arunsajee Sae-Be, Jiraporn Leanpolchareanchai, Piyaporn Plommaithong, Apichat Chatsukit, Shanapa Ratthanakanungthum, Kuntida Wongwattanasan, Tomoki Ota, Sarunyakorn Raowong, Pongtip Sithisarn, Savita Chewchinda, Parichart Naruphontjirakul, Teerasit Termsaithong, Thana Sutthibutpong, Varaporn Buraphacheep Junyaprasert, Khanit Sa-Ngiamsuntorn, Rapepol Bavovada, Pimolpan Pithayanukul, Alexandra E Porter, Pakatip Ruenraroengsak","doi":"10.1080/10717544.2025.2559838","DOIUrl":"10.1080/10717544.2025.2559838","url":null,"abstract":"<p><p>Mango seed kernel extract (MSKE) and its phytochemical compositions were investigated for their anticancer activities and synergistic effects with doxorubicin (DOX) against hepatocellular carcinoma (HCC) in both 2D and 3D culture models. Molecular docking studies were conducted to elucidate the mechanisms of DOX, MSKE, and major phytochemical components against overexpressed HCC-related proteins. Co-delivery of DOX and MSKE demonstrated significant synergistic anticancer activity in both models. A sequential nanotheranostic platform (SNP), consisting of MSKE encapsulated aminated hollow mesoporous silica nanoparticles capped with graphene quantum dots (GQD-MSKE-NH<sub>2</sub>HMSNs) and DOX encapsulated HMSNs (DOX-HMSNs), was synthesized for HCC treatment. GQD conjugation allowed real-time cellular tracking and photothermal therapy (PTT). The SNP exhibited particle sizes of 96.12 ± 5.12 nm for GQD-MSKE-NH<sub>2</sub>HMSNs and 94.99 ± 6.30 nm for DOX-HMSNs, both with positive surface charges. Encapsulation efficiency (%EE) and loading capacity (%LC) of GQD-MSKE-NH<sub>2</sub>HMSNs were 95.50 ± 0.20% and 46.72 ± 1.14%, respectively, while DOX-HMSNs achieved 96.42 ± 2.48 %EE and 29.0 ± 0.70 %LC. GQD-MSKE-NH<sub>2</sub>HMSNs provided PTT and disrupted the tumor microenvironment, collagen type 1, thereby enhancing the penetration of GQD-MSKE-NH<sub>2</sub>HMSNs in 3D-HCC spheroids. In parallel, DOX-HMSNs exhibited a pH-responsive drug release behavior, allowing controlled DOX delivery in the acidic tumor area. Therefore, the SNP demonstrated significantly higher anticancer efficacy than the combination of MSKE and DOX at equivalent concentrations and provided the synergistic effect of the triple combination therapy (herbal adjuvant, PTT and chemotherapy) against HCC.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2559838"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}