Department of Gynecology, The First People's Hospital of Yunnan Province, Kunming University of Science and Technology, Kunming, P.R. China,
Int J Nanomedicine. 2018 Oct 4;13:5991-6007. doi: 10.2147/IJN.S175934. eCollection 2018.
Carbon-based drug delivery systems have attracted great interest because of their excellent photothermal conversion capability and high specific surface area for drug loading. Herein, we report a multifunctional nanoplatform based on hyaluronic acid (HA)-modified and graphene quantum dot (GQD)-gated hollow mesoporous carbon nanoparticle (HMCN) for anticancer drug encapsulation and targeted chemo-photothermal therapy of CD44 receptor-overexpressed cancer cells.
In this design, HMCN was not only used as a nanocarrier with high drug loading content to achieve chemotherapy, but also as a near-infrared absorbing agent to realize photothermal therapy. GQDs could not only prevent premature drug release during blood circulation, but also enhance the chemo-photothermal therapeutic efficacy for complete tumor growth suppression. After being modified with HA, the HA-HMCN(DOX)@GQDs could specifically target cancer cells.
As expected, the as-prepared HMCN exhibited high doxorubicin (DOX)-loading capacity of 410 mg/g and excellent light-to-heat conversion property. The DOX was released from HA-HMCN(DOX)@GQDs in a near-infrared laser and pH stimuli-responsive manner, which could enhance the therapeutic effect. In vitro cell biological experimental results confirmed that the nanoplatform possesses excellent biocompatibility, specifically target CD44 receptor-overexpressing human cervical carcinoma HeLa cells, and has remarkable synergistic chemo-photothermal killing capacity. The in vivo therapeutic studies in HeLa xenografts also showed negligible toxicity of HA-HMCN@GQDs and complete inhibition of tumor growth of HA-HMCN(DOX) @GQDs with near-infrared irradiation.
The excellent therapeutic effects demonstrated in vitro and in vivo suggested the HMCN-based nanoplatform holds potential for efficient dual-responsive targeting drug delivery and synergistic chemo-photothermal therapy.
基于碳的药物传递系统因其优异的光热转换能力和高载药比表面积而受到广泛关注。在此，我们报道了一种基于透明质酸（HA）修饰和石墨烯量子点（GQD）门控中空介孔碳纳米粒子（HMCN）的多功能纳米平台，用于封装抗癌药物和针对 CD44 受体过表达癌细胞的化学-光热治疗。
在本设计中，HMCN 不仅用作具有高载药含量的纳米载体以实现化学疗法，而且还用作近红外吸收剂以实现光热疗法。GQDs 不仅可以防止药物在血液循环过程中过早释放，而且还可以增强化学-光热治疗效果，从而完全抑制肿瘤生长。经 HA 修饰后，HA-HMCN（DOX）@GQDs 可以特异性靶向癌细胞。
正如预期的那样，所制备的 HMCN 表现出高阿霉素（DOX）负载能力为 410 mg/g 和出色的光热转换性能。DOX 可以在近红外激光和 pH 刺激响应下从 HA-HMCN（DOX）@GQDs 中释放，从而增强治疗效果。体外细胞生物学实验结果证实，该纳米平台具有良好的生物相容性，特异性靶向 CD44 受体过表达的人宫颈癌 HeLa 细胞，具有显著的协同化学-光热杀伤能力。在 HeLa 异种移植瘤中的体内治疗研究也表明，HA-HMCN@GQDs 的毒性可以忽略不计，并且在近红外照射下，HA-HMCN（DOX）@GQDs 完全抑制了肿瘤生长。
体外和体内的优异治疗效果表明，基于 HMCN 的纳米平台具有高效双重响应靶向药物传递和协同化学-光热治疗的潜力。
