基于羟基丁基壳聚糖寡糖的温控响应复合纳米粒子：制备、刺激释放与癌症治疗
Thermo-responsive composite nanoparticles based on hydroxybutyl chitosan oligosaccharide: Fabrication, stimulus release and cancer therapy
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影响因子:8.5
分区:生物学2区 Top / 生化与分子生物学2区 应用化学2区 高分子科学2区
发表日期:2024 Sep
作者:
Chong Chen, Weibo Zhang, Pengjie Wang, Yan Zhang, Yinhua Zhu, Yixuan Li, Ran Wang, Fazheng Ren
DOI:
10.1016/j.ijbiomac.2024.133842
摘要
以生物高分子为基础设计温控响应纳米载体在癌症治疗中具有极大的吸引力与挑战性。在本研究中，采用羟基丁基壳聚糖寡糖（HBCOS）与酪蛋白钠（SC）通过静电相互作用和共价交联制备了温控响应复合纳米粒子（CNPs）。CNPs的温度响应行为由纳米粒子中氢键的断裂和链的收缩引起。CNPs表现出浓度无关的温控响应行为、非吸附聚集性及非溶血性，显示出优异的稳定性和温敏性。在42°C时，从CNPs中释放的DOX的初始释放速率和最终释放量高于37°C，表现出温控响应释放，并在较低pH值下更为明显。DOX从CNPs的释放遵循Fick扩散的一级动力学。体外细胞毒性试验证实，载药CNPs具有温控响应的抗肿瘤活性，在42°C培养的HT-29细胞存活率显著低于37°C组。细胞摄取实验证明，载药CNPs在内吞后积聚于细胞质中，并通过升高环境温度促进DOX的释放。本研究成功制备了基于生物高分子的稳定性温敏CNPs，可作为潜在的纳米载体，用于抗癌药物的控制释放以进行癌症治疗。
Abstract
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.