Chen Xiangjun, Li Lu, Fan Qing, Zhang Lingyu, Li Wenting, Hong Wei, Wang Chungang, Zhang Xiuping
School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, P. R. China.
Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin 130024, P. R. China.
Nano Lett. 2025 Jan 29;25(4):1644-1652. doi: 10.1021/acs.nanolett.4c05798. Epub 2025 Jan 14.
Portal vein tumor thrombus (PVTT) is a poor prognostic factor for hepatocellular carcinoma (HCC) patients, highlighting the need for an oral drug delivery system that combines convenience, simplicity, biosafety, and improved patient compliance. Leveraging the unique anatomy of the portal vein and insights from single-cell RNA sequencing of the PVTT tumor microenvironment, we developed oral pellets using CaCO@PDA nanoparticles (NPs) encapsulating both doxorubicin hydrochloride and low molecular weight heparin. These NPs target the tumor thrombus microenvironment, aiming to break down the thrombus barrier and turn the challenge of portal vein blockage into an advantage by enhancing drug delivery efficiency through oral administration. The NPs-based oral delivery system achieved excellent antitumor effects with minimal side effects, demonstrating a promising strategy for managing PVTT in advanced HCC and addressing tumor types associated with vascular invasion and hypercoagulability.
门静脉肿瘤血栓（PVTT）是肝细胞癌（HCC）患者预后不良的因素，这凸显了对一种兼具便利性、简易性、生物安全性且能提高患者依从性的口服给药系统的需求。利用门静脉的独特解剖结构以及PVTT肿瘤微环境的单细胞RNA测序结果，我们开发了口服微丸，其采用碳酸钙@聚多巴胺纳米颗粒（NPs）包裹盐酸多柔比星和低分子量肝素。这些纳米颗粒靶向肿瘤血栓微环境，旨在打破血栓屏障，并通过口服给药提高药物递送效率，将门静脉阻塞的挑战转化为优势。基于纳米颗粒的口服给药系统在副作用最小的情况下实现了优异的抗肿瘤效果，为晚期HCC中PVTT的管理以及解决与血管侵袭和高凝性相关的肿瘤类型提供了一种有前景的策略。
