设计基于生物聚合物的热响应纳米载体对于癌症治疗来说既有趣又具有挑战性。在这项研究中，利用羟丁基壳寡糖（HBCOS）和酪蛋白酸钠（SC）通过静电相互作用和共价交联制备了热响应复合纳米颗粒（CNP）。 CNP 的温度响应行为是由纳米粒子中氢键的断裂和链的收缩引起的。 CNP 表现出与浓度无关的热响应行为、非吸附聚集和非溶血，表明具有优异的稳定性和热敏感性。 42℃时CNPs的DOX初始释放速率和最终释放量均高于37℃，表现出热响应性释放，在较低pH值下更为突出。 DOX 从 CNP 中的释放遵循基于 Fickian 扩散的一级动力学。体外细胞毒性测定证实了负载 DOX 的 CNP 具有热响应性抗肿瘤活性，因为在 42°C 下与负载 DOX 的 CNP 一起孵育的 HT-29 细胞活力显着低于 37°C 下的细胞活力。细胞摄取实验证明，负载DOX的CNPs被内吞后在细胞质中积累，并通过升高环境温度促进DOX的释放。这项研究产生了基于生物聚合物的稳定热敏 CNP，可用作抗癌药物控释的潜在纳米载体，用于癌症治疗。版权所有 © 2024 Elsevier B.V. 保留所有权利。

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.Copyright © 2024 Elsevier B.V. All rights reserved.