Key Laboratory of Micro-Nano Bioanalysis and Drug Screening of Guangxi Higher Education, Pharmaceutical College, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
J Photochem Photobiol B. 2023 Apr;241:112682. doi: 10.1016/j.jphotobiol.2023.112682. Epub 2023 Feb 28.
Efficiently synergistic therapy of hepatocellular carcinoma (HCC) by chemotherapeutic drug and photothermal agent remains a considerable challenge. Here, we report a nanodrug that integrates specific hepatoma-targeted delivery, pH-triggered drug release, and cooperative photothermal-chemotherapy function. By grafting the easily self-assembled CuS@polydopamine (CuS@PDA) nanocapsulation with polyacrylic acid (PAA), an inorganic-organic-polymeric hybrid nanovehicle was developed as a dual photothermal agent and carrier for loading antitumor drug-doxorubicin (DOX) through electrostatic adsorption and chemical linking antibody against GPC3 commonly overexpressed in HCC, resulting in the nanodrug, CuS@PDA/PAA/DOX/GPC3. The multifunctional nanovehicle had excellent biocompatibility, stability, and high photothermal conversion efficiency, due to the rationally designed binary CuS@PDA photothermal agent. The 72-h accumulative drug release in pH 5.5 tumor microenvironment can reach up to 84%, far higher than 15% measured in pH 7.4 condition. Notably, in contrast to the merely 20% survival rate of H9c2 and HL-7702 cells exposed to free DOX, their viabilities in the nanodrug circumstance can maintain 54% and 66%, respectively, suggesting the abated toxicity to the normal cell lines. When exposed to the hepatoma-targeting nanodrug, the viability of HepG2 cells was found to be 36%, which further drastically declined to 10% plus 808-nm NIR irradiation. Moreover, the nanodrug is potent to cause tumor ablation in HCC-modeled mice, and the therapeutic efficacy can be greatly enhanced under NIR stimulus. Histology analyses reveal that the nanodrug can effectively alleviate the chemical damage to heart and liver, as compared to free DOX. This work thus offers a facile strategy for design of targeting anti-HCC nanodrug toward combined photothermal-chemotherapy.
高效协同治疗肝癌（HCC）的化疗药物和光热剂仍然是一个相当大的挑战。在这里，我们报告了一种纳米药物，它集成了特异性肝癌靶向递药、pH 触发药物释放和协同光热化疗功能。通过将易于自组装的 CuS@聚多巴胺（CuS@PDA）纳米胶囊与聚丙烯酸（PAA）接枝，开发了一种无机-有机-聚合物杂化纳米载体，作为通过静电吸附和化学连接抗 HCC 中过表达的 GPC3 的载体制备抗肿瘤药物阿霉素（DOX）的双重光热剂，导致纳米药物，CuS@PDA/PAA/DOX/GPC3。由于合理设计的二元 CuS@PDA 光热剂，多功能纳米载体具有优异的生物相容性、稳定性和高光热转换效率。在 pH 5.5 的肿瘤微环境中，72 小时累积药物释放量可达 84%，远高于 pH 7.4 条件下的 15%。值得注意的是，与暴露于游离 DOX 的 H9c2 和 HL-7702 细胞的仅有 20%存活率相比，它们在纳米药物环境中的活力分别可保持 54%和 66%，表明对正常细胞系的毒性降低。当暴露于肝癌靶向纳米药物时，HepG2 细胞的活力发现为 36%，当再加上 808nm NIR 照射时，活力急剧下降至 10%。此外，该纳米药物在 HCC 模型小鼠中具有强大的肿瘤消融能力，并且在 NIR 刺激下可以大大增强治疗效果。组织学分析表明，与游离 DOX 相比，纳米药物可以有效减轻对心脏和肝脏的化学损伤。这项工作为设计针对 HCC 的靶向纳米药物用于联合光热化疗提供了一种简便的策略。
