Université de Lorraine, CNRS, LCPM, Nancy F-5400, France.
Department of Chemistry/Biology, Georgia State University, Atlanta, Georgia 30303, United States.
ACS Appl Bio Mater. 2021 Mar 15;4(3):2742-2751. doi: 10.1021/acsabm.0c01644. Epub 2021 Feb 10.
In the present study, innovative doxorubicin-loaded nanoparticles (NPs) made of a photosensitive poly(-nitrobenzyl acrylate) (PNBA) hydrophobic matrix and an hydrophilic dextran (Dex) shell were first formulated by the emulsion-solvent evaporation process. Doxorubicin (DOX), a very well-known anticancer drug, was herein chosen as the model. DOX-loaded NPs were successfully produced by covering the hydrophobic PNBA core with Dex chains either physically adsorbed or covalently linked by changing process parameters as the presence of a catalyst (CuBr or CuSO/ascorbic acid). It was then proved that the neutralization of DOX optimized drug loading. DOX loading and release were independent of the coverage mechanism if the catalyst used to covalently link the shell to the core was correctly chosen. Second, the kinetics of DOX release were investigated by simple diffusion or light irradiation of the NPs. Experiments showed that less than 20% of DOX was released by simple diffusion after 48 h in PBS or DMEM media when 45% of DOX released after only 30 s of light irradiation of the NPs. Finally, the impact of the phototriggered DOX release on cell viability was investigated on various cell lines [Caco-2, HepG2, HCT-116, and HT-29 cells as well as murine macrophages (RAW 264.7)]. Cellular mortality was evaluated to be dependent on the cell lines tested. Our approach provided an improved DOX release toward the human liver cancer cell line, and a high internalization of the PNBA-based NPs into HepG2 cells was observed using fluorescence microscopy.
在本研究中，首次通过乳液-溶剂蒸发法制备了由光敏聚（硝基苯丙烯酸酯）（PNBA）疏水基质和亲水葡聚糖（Dex）壳组成的创新阿霉素负载纳米颗粒（NPs）。在此，选择了阿霉素（DOX）作为模型药物，它是一种非常著名的抗癌药物。通过改变工艺参数，用 Dex 链物理吸附或通过共价键连接来覆盖疏水 PNBA 核，成功制备了 DOX 负载的 NPs。然后证明了 DOX 的中和优化了药物负载。如果正确选择用于将壳与核共价连接的催化剂，则 DOX 负载和释放与覆盖机制无关。其次，通过简单扩散或 NPs 的光照射研究了 DOX 的释放动力学。实验表明，在 PBS 或 DMEM 介质中孵育 48 小时后，简单扩散释放的 DOX 少于 20%，而 NPs 仅在 30 秒的光照射后就释放了 45%的 DOX。最后，研究了光触发 DOX 释放对各种细胞系[Caco-2、HepG2、HCT-116 和 HT-29 细胞以及鼠巨噬细胞（RAW 264.7）]的细胞活力的影响。细胞死亡率取决于所测试的细胞系。我们的方法提高了对人肝癌细胞系的 DOX 释放，并通过荧光显微镜观察到基于 PNBA 的 NPs 高度内化进入 HepG2 细胞。
