An inorganic-organic-polymeric nanovehicle for targeting delivery of doxorubicin: Rational assembly, pH-stimulus release, and dual hyperthermia/chemotherapy of hepatocellular carcinoma.
An inorganic-organic-polymeric nanovehicle for targeting delivery of doxorubicin: Rational assembly, pH-stimulus release, and dual hyperthermia/chemotherapy of hepatocellular carcinoma.
复制标题
DOI：
10.1016/j.jphotobiol.2023.112682
复制
发表时间：
2023-02
期刊：
影响因子：
--
通讯作者：
Jianying Yang;Zhao Wang;Chunhong Mo;Haikun Luo;Shuting Li;Qian Mo;You Qin;F. Yang;Xinchun Li
中科院分区：
文献类型：
--
作者：
Jianying Yang;Zhao Wang;Chunhong Mo;Haikun Luo;Shuting Li;Qian Mo;You Qin;F. Yang;Xinchun Li
化疗药物与光热剂协同治疗肝细胞癌（HCC）仍是一个相当大的挑战。在这里，我们报告了一种纳米药物，它集成了特定的肝癌靶向输送，pH触发的药物释放，和合作的光热化疗功能。通过将聚多巴胺（PDA）纳米囊与聚丙烯酸（PAA）接枝，制备了一种无机-有机-聚合物杂化纳米载体，通过静电吸附和化学连接抗肝癌高表达的GPC 3抗体，实现了载药阿霉素（DOX）的双重光热剂和载体，制备了纳米药物CuS@PDA/PAA/DOX/GPC 3。由于合理设计了CuS@PDA光热剂，该多功能纳米载体具有良好的生物相容性、稳定性和较高的光热转换效率。在pH5.5的肿瘤微环境中，72 h累积释药率可达84%，远高于pH7.4时的15%。值得注意的是，与暴露于游离DOX的H9 c2和HL-7702细胞仅20%的存活率相反，它们在纳米药物环境中的存活率可以分别保持54%和66%，这表明对正常细胞系的毒性减弱。当暴露于肝癌靶向纳米药物时，发现HepG 2细胞的存活率为36%，在808 nm NIR照射下进一步急剧下降至10%。此外，该纳米药物能够有效地在HCC模型小鼠中引起肿瘤消融，并且在NIR刺激下可以大大增强治疗效果。组织学分析显示，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。因此，这项工作提供了一个简单的策略，针对联合光热化疗抗肝癌纳米药物的设计。
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.