Key Laboratory of Functional Dairy, Co-constructed by Ministry of Education and Beijing Government, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.
College of Food Science and Engineering, Gansu Agricultural University, Lanzhou 730070, China.
Int J Biol Macromol. 2024 Sep;276(Pt 1):133842. doi: 10.1016/j.ijbiomac.2024.133842. Epub 2024 Jul 14.
Designing thermo-responsive nanocarriers based on biopolymers is fascinating and challenging for cancer therapy. In this study, thermo-responsive composite nanoparticles (CNPs) were prepared using hydroxybutyl chitosan oligosaccharide (HBCOS) and sodium caseinate (SC) via electrostatic interactions and covalent crosslinking. The temperature-responsive behaviors of CNPs were induced by the breakage of hydrogen bonds and the shrinkage of chains in nanoparticles. The CNPs exhibited concentration-independent thermo-responsive behavior, non-adsorption aggregation, and non-hemolysis, suggesting excellent stability and thermo-sensitivity. The initial release rate and final amount of DOX released from CNPs at 42 °C were higher than that at 37 °C, showing a thermo-responsive release, which was also more prominent at lower pH. The release of DOX from CNPs followed first order kinetics based on Fickian diffusion. In vitro cytotoxicity assays confirmed the thermo-responsive antitumor activity of DOX-loaded CNPs as the HT-29 cell viability incubated with DOX-loaded CNPs at 42 °C was significantly lower than that at 37 °C. Cellular uptake experiments proved that DOX-loaded CNPs accumulated in the cytoplasm after being endocytosed and promoted DOX release by increasing environment temperature. This study generated stable thermo-sensitive CNPs based on biopolymers, which can be used as potential nanocarriers for the controlled release of anticancer drugs for cancer therapy.
基于生物聚合物设计温敏纳米载体对于癌症治疗具有吸引力和挑战性。在这项研究中，通过静电相互作用和共价交联，使用羟丁基壳聚糖低聚糖（HBCOS）和酪蛋白酸钠（SC）制备了温敏复合纳米颗粒（CNPs）。纳米颗粒中氢键的破坏和链的收缩导致 CNPs 表现出温度响应行为。CNPs 表现出浓度独立的温敏行为、无吸附聚集和非溶血，表明其具有优异的稳定性和温敏性。在 42°C 时，CNPs 中 DOX 的初始释放率和最终释放量高于 37°C 时，表现出温敏释放，在较低 pH 值下更为明显。基于菲克扩散的一级动力学，研究了 DOX 从 CNPs 中的释放。体外细胞毒性实验证实了载 DOX 的 CNPs 的温敏抗肿瘤活性，因为在 42°C 下孵育载 DOX 的 CNPs 的 HT-29 细胞活力明显低于 37°C 下。细胞摄取实验证明，载 DOX 的 CNPs 被内吞后在细胞质中积累，并通过提高环境温度促进 DOX 释放。本研究基于生物聚合物生成了稳定的温敏 CNPs，可作为用于癌症治疗的抗癌药物控释的潜在纳米载体。
