杨森林 向杨 杨毅军

摘要：原发性肝癌是消化系统最常见的恶性肿瘤之一，其中肝细胞癌（HCC）占90％以上。早期HCC以手术切除为主，且预后较好，然而因HCC起病隐匿，绝大多数患者确诊时已进展至中晚期，手术治疗效果较差，而非手术治疗方式因为普遍存在不良反应大，肿瘤选择性低等问题，疗效也不理想，所以目前中晚期HCC治疗仍是临床工作的难点。纳米粒（NP）尺寸小、比表面积大，具有多种独特的理化性质，成为输送药物、基因及细胞活性因子等治疗剂的潜在载体。纳米递送系统以NP为载体，通过功能化修饰，从时间、空间及剂量上调控药物、基因及细胞活性因子等在体内的代谢及转化，在HCC治疗中展现出巨大的潜力。本文主要介绍了几种常见纳米递送系统，包括有机纳米载体、无机纳米载体、外泌体等在HCC治疗中的现状和优势，总结了基于NP的纳米载体治疗HCC的机制，为新型纳米递送系统的研发提供参考。

关键词：肝细胞癌；纳米技术；药物/基因递送系统；靶向治疗

中图分类号： R735.7  文献标识码： A  文章编号：1000-503X（2024）03-0384-09

DOI：10.3881/j.issn.1000-503X.15669

Advances in Nanotechnology-Based Drug Delivery Systems in the Treatment of Hepatocellular Carcinoma

YANG Senlin，XIANG Yang，YANG Yijun

Department of Hepatobiliary Surgery，Haikou Affiliated Hospital of Central South University Xiangya School of Medicine，Haikou 570208，China

Corresponding author：XIANG Yang Tel：18876163917，E-mail：xiangyang200611@126.com

ABSTRACT：Primary liver cancer is one of the most common malignant tumors of the digestive system，of which hepatocellular carcinoma （HCC） accounts for more than 90% of the total cases.The patients with early HCC treated by surgical resection generally demonstrate good prognosis.However，due to the insidious onset，HCC in the vast majority of patients has progressed to the mid-to-late stage when being diagnosed.As a result，surgical treatment has unsatisfactory effects，and non-surgical treatment methods generally have severe side effects and low tumor selectivity.Nanoparticles （NP） with small sizes，large specific surface areas，and unique physical and chemical properties have become potential carriers for the delivery of therapeutic agents such as drugs，genes，and cytokines.The nano-delivery systems with NP as the carrier can regulate the metabolism and transformation of drugs，genes，and cytokines in vivo from time，space，and dose via functional modification，showing great potential in the treatment of HCC.This paper introduces the current status and advantages of several common nano-delivery systems，including organic nano-carriers，inorganic nano-carriers，and exosomes，in the treatment of HCC.Furthermore，this paper summarizes the mechanisms of NP-based nano-carriers in treating HCC and provides reference for the development of new nano-delivery systems.

Key words：hepatocellular carcinoma；nanotechnology；drug/gene-delivery system；targeted therapy

Acta Acad Med Sin，2024，46（3）：384-392

原发性肝癌是消化系统最常见的恶性肿瘤之一，其中肝细胞癌（hepatocellular carcinoma，HCC）占90％以上，死亡率约为8.3％［1］。HCC的发病与多种因素相关，如酒精性肝硬化、糖尿病、乙型和丙型肝炎、吸烟、铁超载等［2］。目前HCC的治疗方法主要有手术治疗（肝切除和肝移植）和非手术治疗（化疗栓塞、放疗、微波消融和系统治疗）。早期HCC以手术切除为主，预后较好；然而由于HCC起病隐匿，确诊病例多为中晚期，单纯手术治疗效果较差。……