Pharmaceutical Analysis Division, School of Pharmacy, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China.
Pharmaceutical Analysis Division, School of Pharmacy, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China; School of Medicine, Xiamen University, Xiang-an South Road, Xiamen 361102, China.
J Photochem Photobiol B. 2022 Aug;233:112487. doi: 10.1016/j.jphotobiol.2022.112487. Epub 2022 May 31.
Herein, we present the facile design and construction of a nanodrug system integrating targeted drug delivery and synergistic chemo-photothermal antitumor activity. MoS nanosheets were synthesized and modified by αβ integrin binding peptide (Arg-Gly-Asp, RGD) using lipoic acid functionalized polyethylene glycol (LA-PEG-COOH), forming a well dispersed and targeted delivery nanocarrier. Further, covalent coupling of antitumor drug, thiolated doxorubicin (DOX) via disulfide linkage resulted in a novel nanodrug, RGD/MoS/DOX. The prepared nanocarrier showed favorable stability, biocompatibility and photothermal conversion efficiency. Fluorescence imaging revealed that Hela cells could endocytose far more nanodrug than H9c2 normal myocardial cells due to the targeted delivery characteristic. Particularly, GSH-induced disulfide bond cleavage facilitated the effective release of DOX from the nanodrug in the tumor microenvironment. The survival rate of Hela cells incubated with the nanodrug for 48 h was 22.2 ± 1.2%, which dramatically reduced to 8.9 ± 1.4% in combination with 808 nm NIR irradiation, demonstrating powerful photothermal induced tumor-killing efficacy. In contrast, the survival rates of H9c2 cells treated by the nanodrug and free DOX were 68.5 ± 2.6% and 6.7 ± 2.6%, respectively, an indication of the notably alleviated cardiotoxicity of the designed nanodrug. The cell apoptosis experiment further verified the synergistic chemo-photothermal effect, thus paving a way toward design of high-efficiency and low-toxicity antitumor nanodrug.
本文提出了一种将靶向药物输送和协同化疗-光热抗肿瘤活性集成的纳米药物系统的简便设计和构建。通过使用巯基化聚乙二醇（LA-PEG-SH）修饰的脂肪酸功能化聚乙二醇（LA-PEG-COOH），合成并修饰了 MoS 纳米片，形成了分散良好且具有靶向输送能力的纳米载体。进一步通过二硫键将抗癌药物，硫代阿霉素（DOX）共价偶联，得到了一种新型的纳米药物，RGD/MoS/DOX。所制备的纳米载体表现出良好的稳定性、生物相容性和光热转换效率。荧光成像显示，由于靶向输送的特点，Hela 细胞比 H9c2 正常心肌细胞能够内吞更多的纳米药物。特别是，谷胱甘肽（GSH）诱导的二硫键断裂促进了 DOX 从纳米药物在肿瘤微环境中的有效释放。孵育 48 h 后，与 808 nm NIR 照射联合使用时，Hela 细胞的存活率为 22.2±1.2%，显著降低至 8.9±1.4%，表明强大的光热诱导肿瘤杀伤功效。相比之下，用纳米药物和游离 DOX 处理的 H9c2 细胞的存活率分别为 68.5±2.6%和 6.7±2.6%，表明设计的纳米药物明显减轻了心脏毒性。细胞凋亡实验进一步验证了协同化疗-光热效应，为设计高效低毒的抗肿瘤纳米药物铺平了道路。
