Bai Jiafan, Liu Yuhao, Chen Xiangli, Wang Linyu, Shi Jie, Liu Hongyan, Peng Wenzhen, Zhao Yuancong, Weng Jie, Zhi Wei, Wang Jianxin
College of Medicine and School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Department of Biochemistry and Molecular Biology, College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Colloids Surf B Biointerfaces. 2025 Nov;255:114962. doi: 10.1016/j.colsurfb.2025.114962. Epub 2025 Jul 17.
This study aims to address the issue of immune clearance and inaccurate targeting of drug-loaded nanoparticles during intravenous injection, which may lead to partial drug release into non target tissues or organs, damage to normal tissues and low drug utilization. Herein, multi-drug co-delivery nanoparticles with intratumoral long retention capability were developed for melanoma treatment. This study adopted a dual drug loading strategy of curcumin and dexamethasone and designed a drug-loaded nano-system based on polyglutamic acid and caffeic acid. The results indicate that the introduction of caffeic acid endowed nanoparticles with the property of long-term retention in melanoma sites, while also obtaining a certain inhibitory effect on melanoma growth and good antioxidant properties. To make nanoparticles more stable in water environment, we employed esterification reaction to introduce ester bond to enhance the water resistance of nanoparticles, thus giving them stability in water environment. Two drugs with different hydrophilicity were co-loaded into nanoparticles through grafting and π-π stacking. The experimental results in vitro and in vivo indicate that such strategy and design have achieved long-term retention of nanoparticles at tumor site, and meanwhile allow nanoparticles to effectively inhibit the growth and metastasis of tumor cells, achieving ideal therapeutic effects on melanoma treatment.
本研究旨在解决静脉注射过程中载药纳米颗粒的免疫清除和靶向不准确问题，这可能导致部分药物释放到非靶组织或器官中，损害正常组织并降低药物利用率。在此，开发了具有肿瘤内长期滞留能力的多药共递送纳米颗粒用于黑色素瘤治疗。本研究采用姜黄素和地塞米松的双药负载策略，并设计了一种基于聚谷氨酸和咖啡酸的载药纳米系统。结果表明，咖啡酸的引入赋予纳米颗粒在黑色素瘤部位长期滞留的特性，同时对黑色素瘤生长也有一定的抑制作用，并具有良好的抗氧化性能。为使纳米颗粒在水环境中更稳定，我们采用酯化反应引入酯键以增强纳米颗粒的耐水性，从而使其在水环境中具有稳定性。通过接枝和π-π堆积将两种亲水性不同的药物共负载到纳米颗粒中。体外和体内实验结果表明，这种策略和设计实现了纳米颗粒在肿瘤部位的长期滞留，同时使纳米颗粒能够有效抑制肿瘤细胞的生长和转移，对黑色素瘤治疗取得了理想的治疗效果。
