Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry , Wuhan University , Wuhan 430072 , People's Republic of China.
ACS Appl Mater Interfaces. 2019 Oct 23;11(42):38385-38394. doi: 10.1021/acsami.9b11263. Epub 2019 Oct 9.
To enhance the treatment efficiency in tumor therapy, we developed a tumor-targeting protein-based delivery system, DOX&ICG@BSA-KALA/Apt, to efficiently integrate multimodal therapy with tumor imaging and realize synchronous photodynamic therapy/photothermal therapy/chemotherapy. In the delivery system, a chemotherapeutic drug (doxorubicin, DOX) and an optotheranostic agent (indocyanine green, ICG) were co-loaded in bovine serum albumin (BSA) via a hydrophobic-interaction-induced self-assembly to form stable DOX&ICG@BSA nanoparticles. After the decoration of a surface layer composed of a tumor-targeting aptamer (AS1411) and a cell-penetrating peptide (KALA), the obtained DOX&ICG@BSA-KALA/Apt nanoparticles exhibit a significantly improved multimodal cancer therapeutic efficiency due to the enhanced cancer cellular uptake mediated by AS1411 and KALA. In vitro and in vivo studies show that the multimodal theranostic system can efficiently inhibit tumor growth. In addition, the near-infrared fluorescent/photothermal dual-mode imaging enables accurate visualization of the therapeutic action in tumor sites. This study provides a facile strategy to construct self-assembled multimodal theranostic systems, and the functional protein-based theranostic system prepared holds great promise in multimodal cancer therapeutics.
为了提高肿瘤治疗的疗效，我们开发了一种基于肿瘤靶向蛋白的递药系统，DOX&ICG@BSA-KALA/Apt，以高效整合多模态治疗与肿瘤成像，并实现光动力治疗/光热治疗/化学治疗的同步。在递药系统中，通过疏水相互作用诱导的自组装将化疗药物（阿霉素，DOX）和光热治疗剂（吲哚菁绿，ICG）共载于牛血清白蛋白（BSA）中，形成稳定的 DOX&ICG@BSA 纳米颗粒。经肿瘤靶向适体（AS1411）和穿膜肽（KALA）组成的表面层修饰后，所得的 DOX&ICG@BSA-KALA/Apt 纳米颗粒由于 AS1411 和 KALA 介导的增强的癌细胞摄取，表现出显著提高的多模态癌症治疗效率。体外和体内研究表明，多模态治疗系统能够有效地抑制肿瘤生长。此外，近红外荧光/光热双模成像能够准确地可视化肿瘤部位的治疗作用。本研究提供了一种构建自组装多模态治疗系统的简便策略，所制备的基于功能蛋白的治疗系统在多模态癌症治疗中具有广阔的应用前景。
