Hu Yuefang, Zhang Liangliang, Chen Shengyu, Hou Li, Zhao Shulin, Huang Yong, Liang Hong
State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University Guilin 541004 China
College of Materials and Environmental Engineering, Hezhou University Hezhou 542899 China.
Nanoscale Adv. 2021 Oct 22;3(24):6869-6875. doi: 10.1039/d1na00595b. eCollection 2021 Dec 7.
Cancer therapy faces considerable challenges related to improving treatment efficiency and overcoming damage to healthy cells. To address these concerns, a strategy for tumor microenvironment-induced cancer imaging/drug release and synergistic chemo-photothermal therapy (chemo/PTT) is proposed in this study. Carbon dots with near-infrared (NIR) absorption and emission, referred to as RCDs, were first prepared and covalently coupled with a Pt(iv) prodrug to form a complex, referred to as RCD-Pt(iv). The surface of the prepared complex was then coated with the polyethylene glycol-chitosan-2,3-dimethylmaleic anhydride polymer (PEG-CS-DA) to obtain a tumor-targeted multifunctional nanoprobe (RCD-Pt(iv)/PEG-CS-DA). When the nanoprobe RCD-Pt(iv)/PEG-CS-DA entered the tumor cells, the acidic environment of the tumor cells allowed rapid PEG-CS-DA hydrolysis and RCD-Pt(iv) release. High levels of glutathione (GSH) in cancer cells reduced Pt(iv) to Pt(ii) and released the RCDs, resulting in cancer tissue imaging and targeted Pt(ii) release. Meanwhile, Pt(ii) collected in the tumor tissues could realize targeted chemotherapy, and the RCDs in the tumor tissues absorbed light energy under NIR light irradiation to produce a large amount of heat to quickly eliminate cancer cells. Thus, cancer tissue imaging/targeted drug release and synergistic chemo/PTT were achieved simultaneously.
癌症治疗在提高治疗效率和克服对健康细胞的损害方面面临着巨大挑战。为了解决这些问题,本研究提出了一种肿瘤微环境诱导的癌症成像/药物释放及协同化疗-光热疗法(化疗/光热疗法)策略。首先制备了具有近红外(NIR)吸收和发射特性的碳点,称为RCDs,并将其与铂(IV)前药共价偶联形成一种复合物,称为RCD-Pt(IV)。然后在制备的复合物表面包覆聚乙二醇-壳聚糖-2,3-二甲基马来酸酐聚合物(PEG-CS-DA),以获得一种肿瘤靶向多功能纳米探针(RCD-Pt(IV)/PEG-CS-DA)。当纳米探针RCD-Pt(IV)/PEG-CS-DA进入肿瘤细胞时,肿瘤细胞的酸性环境使PEG-CS-DA快速水解并释放RCD-Pt(IV)。癌细胞中高水平的谷胱甘肽(GSH)将Pt(IV)还原为Pt(II)并释放出RCDs,从而实现癌症组织成像和靶向Pt(II)释放。同时,在肿瘤组织中聚集的Pt(II)可实现靶向化疗,肿瘤组织中的RCDs在近红外光照射下吸收光能产生大量热量,迅速消除癌细胞。因此,同时实现了癌症组织成像/靶向药物释放和协同化疗/光热疗法。