State Key Laboratory of Quality Research in Chinese Medicines, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR 999078, China.
Department of Interventional Radiology, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou 646000, China.
ACS Appl Mater Interfaces. 2023 Mar 8;15(9):11431-11443. doi: 10.1021/acsami.2c18267. Epub 2023 Feb 27.
Transarterial chemoembolization (TACE) is commonly used for treating advanced hepatocellular carcinoma (HCC). However, the instability of lipiodol-drug emulsion and the altered tumor microenvironment (TME, such as hypoxia-induced autophagy) postembolization are responsible for the unsatisfactory therapeutic outcomes. Herein, pH-responsive poly(acrylic acid)/calcium phosphate nanoparticles (PAA/CaP NPs) were synthesized and used as the carrier of epirubicin (EPI) to enhance the efficacy of TACE therapy through autophagy inhibition. PAA/CaP NPs have a high loading capacity of EPI and a sensitive drug release behavior under acidic conditions. Moreover, PAA/CaP NPs block autophagy through the dramatic increase of intracellular Ca content, which synergistically enhances the toxicity of EPI. TACE with EPI-loaded PAA/CaP NPs dispersed in lipiodol shows an obvious enhanced therapeutic outcome compared to the treatment with EPI-lipiodol emulsion in an orthotopic rabbit liver cancer model. This study not only develops a new delivery system for TACE but also provides a promising strategy targeting autophagy inhibition to improve the therapeutic effect of TACE for the HCC treatment.
经动脉化疗栓塞（TACE）是治疗晚期肝细胞癌（HCC）的常用方法。然而，碘油-药物乳剂的不稳定性和栓塞后肿瘤微环境（TME，如缺氧诱导的自噬）的改变是导致治疗效果不理想的原因。本文合成了 pH 响应性聚丙烯酸/磷酸钙纳米粒子（PAA/CaP NPs），并将其用作表阿霉素（EPI）的载体，通过抑制自噬来增强 TACE 治疗的效果。PAA/CaP NPs 对 EPI 具有高载药能力，并在酸性条件下具有敏感的药物释放行为。此外，PAA/CaP NPs 通过显著增加细胞内 Ca 含量来阻断自噬，从而协同增强 EPI 的毒性。与 EPI-载 lipiodol 乳剂相比，在原位兔肝癌模型中，用分散在 lipiodol 中的载 EPI-PAA/CaP NPs 的 TACE 显示出明显增强的治疗效果。这项研究不仅开发了用于 TACE 的新递送系统，而且还提供了一种有前途的抑制自噬的策略，以提高 TACE 治疗 HCC 的疗效。
