State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
Theranostics. 2021 May 13;11(14):7057-7071. doi: 10.7150/thno.60427. eCollection 2021.
Development of nanosystems that can be integrated with macrophages (MAs), an emerging carrier system, for effective tumor therapy remains to be challenging. We report here the development of MAs specifically loaded with hyaluronic acid (HA) nanogels (NGs) encapsulated with a photothermal agent of polypyrrole (PPy) and anticancer drug doxorubicin (DOX) (HA/DOX@PPy NGs) for tumor homing and combination photothermo-chemotherapy. Cystamine dihydrochloride-crosslinked HA NGs were first prepared through a double emulsification method, then loaded with PPy via an oxidization polymerization and physically encapsulated with DOX. The created HA/DOX@PPy NGs were well characterized and subjected to be endocytosed by MAs (MAs-NGs). The MAs-mediated tumor-homing property, phenotype changes and photothermal performance of MAs-NGs were investigated , and a subcutaneous tumor model was also established to confirm their targeting capability and enhanced antitumor therapy effect . The generated hybrid NGs possess a size around 77 nm and good colloidal stability, and can be specifically endocytosed by MAs without appreciably affecting their normal biofunctionalities. In particular, NG-loaded MAs display excellent cancer cell and tumor homing property. Systemic administration of the MAs-NGs leads to the significant inhibition of a subcutaneous tumor model through combination photothermo-chemotherapy under laser irradiation. The developed hybrid HA-based NG nanosystem incorporated with PPy and DOX fully integrates the coordination and heating property of PPy to regulate the optimized DOX release in the tumor region with the assistance of MA-mediated tumor homing, providing a promising cell therapy strategy for enhanced antitumor therapy.
开发能够与巨噬细胞（MA）整合的纳米系统（一种新兴的载体系统）用于有效的肿瘤治疗仍然具有挑战性。我们在此报告了专门装载透明质酸（HA）纳米凝胶（NG）的 MA 的开发，这些纳米凝胶包裹有聚吡咯（PPy）光热剂和抗癌药物阿霉素（DOX）（HA/DOX@PPy NG），用于肿瘤归巢和联合光热化学治疗。首先通过双重乳化法制备巯基二盐酸盐交联的 HA NG，然后通过氧化聚合加载 PPy 并通过物理包封 DOX。对所创建的 HA/DOX@PPy NG 进行了很好的表征，并被 MA（MA-NG）内吞。研究了 MA-NG 的 MA 介导的肿瘤归巢特性、表型变化和光热性能，并建立了皮下肿瘤模型以确认其靶向能力和增强的抗肿瘤治疗效果。所产生的杂交 NG 具有约 77nm 的尺寸和良好的胶体稳定性，并且可以被 MA 特异性内吞而不会明显影响其正常的生物功能。特别是，载有 NG 的 MA 显示出优异的癌细胞和肿瘤归巢特性。通过激光照射下的联合光热化学治疗，系统给予 MA-NG 可显著抑制皮下肿瘤模型。该开发的基于 HA 的杂交 NG 纳米系统与 PPy 和 DOX 结合，充分整合了 PPy 的协调和加热特性，以在 MA 介导的肿瘤归巢的辅助下调节肿瘤区域中 DOX 的最佳释放，为增强抗肿瘤治疗提供了一种有前途的细胞治疗策略。
