肝细胞癌（HCC）是全球癌症相关死亡的主要原因。替米沙坦（TLM）是一种BSC II类药物，据报道具有对HCC的抗增殖活性。然而，其治疗活性受到生物利用度低和分布不可预测的限制。本研究旨在通过被乳糖（LCH）修饰的壳聚糖纳米颗粒作为传递系统，通过被动和主动靶向途径增强TLM在HCC管理中的肝组织摄取。体外细胞毒性和细胞摄取研究表明，TLM-LCH纳米颗粒显著（p < 0.05）增强了TLM的抗增殖活性和细胞摄取率。体内生物利用度和肝组织分布研究表明，TLM-LCH纳米颗粒显著（p < 0.05）增强了TLM在血浆和肝组织中的浓度。TLM-LCH纳米颗粒对TLM的肝摄取相对于未修饰纳米颗粒提高了2倍，比普通TLM悬浮液提高了5倍。N-亚硝基二乙酰胺诱导的HCC模型的体内研究表明，通过LCH纳米颗粒给予TLM改善了肝脏组织学，并且相对于普通TLM和TLM载荷未修饰纳米颗粒的组，血清甲胎蛋白（AFP）、基质金属蛋白酶2（MMP-2）和血管内皮细胞生长因子（VEGF）水平更低，肝重指数和肝重指数较低。这些结果反映了LCH纳米颗粒作为肝靶向递送系统在HCC治疗中的高潜力。

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. Telmisartan (TLM), a BSC class II drug, has been reported to have antiproliferative activity in HCC. However, its therapeutic activity is limited by poor bioavailability and unpredictable distribution. This work aimed to enhance TLM's liver uptake for HCC management through passive and active targeting pathways utilizing chitosan nanoparticles decorated with lactose (LCH NPs) as a delivery system. In vitro cell cytotoxicity and cellular uptake studies indicated that TLM-LCH NPs significantly (p < 0.05) enhanced the antiproliferative activity and cellular uptake percentage of TLM. In vivo bioavailability and liver biodistribution studies indicated that TLM-LCH NPs significantly (p < 0.05) enhanced TLM concentrations in plasma and the liver. The relative liver uptake of TLM from TLM-LCH NPs was 2-fold higher than that of unmodified NPs and 5-fold higher than that of plain TLM suspension. In vivo studies of a N-nitrosodiethylamine-induced HCC model revealed that administration of TLM through LCH NPs improved liver histology and resulted in lower serum alpha-fetoprotein (AFP), matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF) levels, and liver weight index compared to plain TLM and TLM-loaded unmodified NPs. These results reflected the high potentiality of LCH NPs as a liver-targeted delivery system for TLM in the treatment of HCC.