School of Biomedical Engineering, Sun Yat-sen University, Shenzhen, 518057, P.R. China.
Department of Pediatrics, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, P. R. China.
Biomater Sci. 2022 May 4;10(9):2263-2274. doi: 10.1039/d2bm00027j.
Using biocompatible polymers with potential therapeutic activity is an appealing strategy for the development of new functional drug carriers. In this study, we report the synthesis of therapeutic poly(-coumaric acid) (PCA) from -coumaric acid, a common plant phenolic acid with multiple bioactivities. The prepared PCA was formulated into nanoparticles (NPs) using the nanoprecipitation method and docetaxel (DTX) was encapsulated to form DTX-loaded PCA NPs (DTX@PCA NPs). Their potential as a nanocarrier for anticancer drug delivery was systematically evaluated. The DTX@PCA NPs not only had a small particle size and good stability, but also exhibited superior anticancer activity, anti-metastasis ability compared with free drugs, and preferable cellular uptake by tumor cells. In addition, the three-dimensional tumor spheroid assay revealed the effective tumor penetration and anticancer activity of the DTX@PCA NPs. Importantly, the DTX@PCA NPs preferentially accumulated in tumors and prolonged systemic circulation, significantly inhibiting tumor growth and simultaneously attenuating the side effects of DTX. Interestingly, the blank PCA NPs themselves also exhibited additional tumor suppression activity to some extent with high biosafety, further indicating the significant potential of PCA as a novel self-therapeutic nanocarrier for anticancer drug delivery and enhanced cancer therapy.
使用具有潜在治疗活性的生物相容性聚合物是开发新型功能药物载体的一种有吸引力的策略。在本研究中,我们报告了从 - 咖啡酸合成治疗性聚( - 咖啡酸)(PCA), - 咖啡酸是一种具有多种生物活性的常见植物酚酸。所制备的 PCA 采用纳米沉淀法制成纳米粒子(NPs),并包封多西他赛(DTX)以形成载多西他赛的 PCA NPs(DTX@PCA NPs)。系统评估了它们作为抗癌药物传递纳米载体的潜力。与游离药物相比,DTX@PCA NPs 不仅具有较小的粒径和良好的稳定性,而且表现出优异的抗癌活性、抗转移能力和肿瘤细胞的摄取能力。此外,三维肿瘤球体测定显示 DTX@PCA NPs 具有有效的肿瘤穿透和抗癌活性。重要的是,DTX@PCA NPs 优先在肿瘤中积累并延长系统循环,显著抑制肿瘤生长,同时减轻 DTX 的副作用。有趣的是,空白 PCA NPs 本身也表现出一定程度的额外肿瘤抑制活性,具有较高的生物安全性,进一步表明 PCA 作为一种新型自治疗性纳米载体用于抗癌药物传递和增强癌症治疗的巨大潜力。