载多柔比星的聚多巴胺/金空心纳米球用于非小细胞肺癌的化疗-光热联合治疗。

PURPOSE: The chemotherapeutic agent doxorubicin (DOX) is limited by its cardiotoxicity, posing challenges in its application for non-small cell lung cancer (NSCLC). This study aims to explore the efficacy of polydopamine/Au nanoparticles loaded with DOX for chemotherapy and photothermal therapy in NSCLC to achieve enhanced efficacy and reduced toxicity. METHODS: Hollow polydopamine (HPDA)/Au@DOX was synthesized via polydopamine chemical binding sacrificial template method. Morphology was characterized using transmission electron microscopy, particle size and potential were determined using dynamic light scattering, and photothermal conversion efficiency was assessed using near-infrared (NIR) thermal imaging. Drug loading rate and in vitro drug release were investigated. In vitro, anti-tumor experiments were conducted using CCK-8 assay, flow cytometry, and live/dead cell staining to evaluate the cytotoxicity of HPDA/Au@DOX on A549 cells. Uptake of HPDA/Au@DOX by A549 cells was detected using the intrinsic fluorescence of DOX. The in vivo anti-metastasis and anti-tumor effects of HPDA/Au@DOX were explored in mouse lung metastasis and subcutaneous tumor models, respectively. RESULTS: HPDA/Au@DOX with a particle size of (164.26±3.25) nm, a drug loading rate of 36.31%, and an encapsulation efficiency of 90.78% was successfully prepared. Under 808 nm laser irradiation, HPDA/Au@DOX accelerated DOX release and enhanced uptake by A549 cells. In vitro photothermal performance assessment showed excellent photothermal conversion capability and stability of HPDA/Au@DOX under NIR laser irradiation. Both in vitro and in vivo experiments demonstrated that the photothermal-chemotherapy combination group (HPDA/Au@DOX+NIR) exhibited stronger anti-metastatic and anti-tumor activities compared to the monotherapy group (DOX). CONCLUSION: HPDA/Au@DOX nanosystem demonstrated excellent photothermal effect, inhibiting the growth and metastasis of A549 cells. This nanosystem achieves the combined effect of chemotherapy and photothermal, making it promising for NSCLC treatment.

目的：阿霉素（DOX）作为一种化疗药物，其心脏毒性限制了其在非小细胞肺癌（NSCLC）中的应用。本研究旨在探索载多柔比星的聚多巴胺/金纳米粒子（HPDA/Au@DOX）用于 NSCLC 化疗和光热治疗的疗效，以实现增强疗效和降低毒性的目的。

方法：采用聚多巴胺化学结合牺牲模板法合成空心聚多巴胺（HPDA）/Au@DOX。采用透射电子显微镜对形貌进行表征，采用动态光散射法测定粒径和电位，采用近红外（NIR）热成像评估光热转换效率。考察药物载药量和体外药物释放。体外采用 CCK-8 法、流式细胞术和活/死细胞染色实验评价 HPDA/Au@DOX 对 A549 细胞的细胞毒性。采用 DOX 的本征荧光检测 A549 细胞对 HPDA/Au@DOX 的摄取。在小鼠肺转移和皮下肿瘤模型中分别探讨 HPDA/Au@DOX 的体内抗转移和抗肿瘤作用。

结果：成功制备了粒径为（164.26±3.25）nm、载药量为 36.31%、包封率为 90.78%的 HPDA/Au@DOX。在 808nm 激光照射下，HPDA/Au@DOX 加速 DOX 释放并增强 A549 细胞摄取。体外光热性能评价结果表明，HPDA/Au@DOX 在近红外激光照射下具有优异的光热转换能力和稳定性。体外和体内实验均表明，与单一药物治疗组（DOX）相比，光热-化学联合治疗组（HPDA/Au@DOX+NIR）具有更强的抗转移和抗肿瘤活性。

结论：HPDA/Au@DOX 纳米系统表现出优异的光热效应，抑制了 A549 细胞的生长和转移。该纳米系统实现了化疗和光热的联合作用，有望用于 NSCLC 的治疗。