{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:16:33Z","timestamp":1791299793874,"version":"4.1.0"},"reference-count":156,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172599"],"award-info":[{"award-number":["82172599"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170143"],"award-info":[{"award-number":["82170143"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370191"],"award-info":[{"award-number":["82370191"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200160"],"award-info":[{"award-number":["82200160"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) ranks as the second most lethal malignancy worldwide, presenting formidable therapeutic challenges including tumor heterogeneity, complex microenvironment, and inefficient drug delivery. Conventional therapies such as surgery, chemotherapy, and immunotherapy are limited by systemic toxicity, drug resistance, and poor targeting specificity. Mesenchymal stem cells (MSCs) have emerged as promising drug delivery vehicles, leveraging their innate tumor-homing capacity, immunomodulatory properties, and exosome-mediated cargo transport. Preclinical studies demonstrate that MSC-based systems triple drug accumulation in tumors and synergize with immunotherapy, extending survival in HCC models. This review systematically examines recent advances in MSC-based delivery systems for HCC, focusing on engineering strategies to enhance targeting precision and controlled drug release, including genetic modification, exosome engineering, and stimuli-response systems. Despite progress, challenges such as MSC heterogeneity and scalable production persist. Emerging solutions like single-cell RNA sequencing for subpopulation selection and 3D bioprinting for standardized culture are highlighted. This work provides a roadmap for developing MSC-based precision therapies, bridging translational gaps in HCC treatment.<\/jats:p>","DOI":"10.3390\/bioengineering12111206","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:11:16Z","timestamp":1762254676000},"page":"1206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mesenchymal Stem Cell-Mediated Targeted Drug Delivery Systems for Hepatocellular Carcinoma: Current Advances and Future Directions"],"prefix":"10.3390","volume":"12","author":[{"given":"Yang","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Toxicology, School of Medicine and Public Health, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Medicine and Public Health, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Fei","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of General Surgery of The Affiliated Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Medicine and Public Health, Zhejiang University, Hangzhou 310058, China"},{"name":"Department of Hematology of First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0799-2340","authenticated-orcid":false,"given":"Hua","family":"Naranmandura","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Medicine and Public Health, Zhejiang University, Hangzhou 310058, China"},{"name":"Department of Hematology of First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"ref_1","unstructured":"Global Burden of Disease Cancer Collaboration (2019). 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