Lin BeiBei, Lin Peizhen, Zhang Xiaobi, Liao Yingyi, Yu Yinfei, Xu Xuegu, Wang Xiaoling
State Key Laboratory of Ophthalmology, Optometry and Visual Science, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Int J Nanomedicine. 2024 Dec 31;19:14105-14124. doi: 10.2147/IJN.S490485. eCollection 2024.
Developing carrier-free nanomedicines via self-assembly of two antitumor drug molecules is a potential strategy for enhancing the combination treatment of tumors. Similarly, conventional chemotherapy combined with photodynamic therapy may synergistically improve the antitumor effect while minimizing the adverse reactions associated with antitumor treatment. Hyaluronic acid (HA) can bind to overexpressed HA receptors on the tumor cell surface, increasing cell internalization and resulting in good tumor-targeting properties.
Herein, we propose an easy and environmentally friendly approach for fabricating a novel formulation of carrier-free pure nanodrugs through self-assembly of the antitumor drug doxorubicin (DOX) and the photosensitizer chlorin e6 (Ce6), followed by sequential modification with HA to achieve simultaneous and targeted photodynamic therapy and chemotherapy.
The fabricated HA-DOX-Ce6 nanoparticles (NPs) exhibited enhanced drug loading and stability while possessing the properties of near-infrared fluorescence imaging, self-targeting drug delivery, and combined photodynamic therapy and chemotherapy.
HA-DOX-Ce6 NPs, along with laser irradiation, effectively suppressed tumor development both in vitro and in vivo with minimal side effects. Overall, this biomaterial-based, carrier-free drug delivery system, in combination with cotargeted therapies, has shown potential for considerable improvements in treatment outcomes and patient prognosis.
通过两种抗肿瘤药物分子的自组装来开发无载体纳米药物是增强肿瘤联合治疗的一种潜在策略。同样,传统化疗与光动力疗法联合使用可能会协同提高抗肿瘤效果,同时将与抗肿瘤治疗相关的不良反应降至最低。透明质酸(HA)可与肿瘤细胞表面过度表达的HA受体结合,增加细胞内化并产生良好的肿瘤靶向特性。
在此,我们提出一种简便且环保的方法,通过抗肿瘤药物阿霉素(DOX)和光敏剂二氢卟吩e6(Ce6)的自组装制备新型无载体纯纳米药物制剂,随后用HA进行顺序修饰,以实现同步靶向光动力疗法和化疗。
制备的HA-DOX-Ce6纳米颗粒(NPs)表现出增强的载药量和稳定性,同时具有近红外荧光成像、自靶向药物递送以及光动力疗法与化疗相结合的特性。
HA-DOX-Ce6 NPs与激光照射一起,在体外和体内均能有效抑制肿瘤发展,且副作用最小。总体而言,这种基于生物材料的无载体药物递送系统与共靶向疗法相结合,已显示出在改善治疗效果和患者预后方面具有巨大潜力。