基于羟基丁基壳聚糖寡糖的热响应复合纳米颗粒：制造，刺激释放和癌症治疗
Thermo-responsive composite nanoparticles based on hydroxybutyl chitosan oligosaccharide: Fabrication, stimulus release and cancer therapy
影响因子:8.50000
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
摘要
设计基于生物聚合物的热响应性纳米载体令人着迷，并且对癌症治疗充满挑战。在这项研究中，使用羟丁丁基壳聚糖寡糖（HBCOS）和Caseatinate（SC）（SC）通过静电相互作用和共价交联制备热响应复合纳米颗粒（CNP）。 CNP的温度响应行为是通过氢键的断裂和纳米颗粒中链的收缩引起的。 CNP表现出独立于浓度的热响应行为，非吸附聚集和非溶解性，表明稳定性良好和热敏感性。在42°C下从CNP释放的初始释放速率和最终量的DOX高于37°C下的DOX，显示了热响应性释放，在较低的pH值下也更为突出。从CNP中释放DOX遵循基于Fickian扩散的一级动力学。体外的细胞毒性测定确认DOX负载的CNP的热反应抗肿瘤活性是在42°C下与DOX载荷CNP孵育的HT-29细胞生存能力明显低于37°C时的HT-29细胞活性。细胞摄取实验证明，在内吞和促进DOX释放后，通过升高环境温度释放了DOX负载的CNP。这项研究基于生物聚合物产生了稳定的热敏感CNP，可以用作控制抗癌药物进行癌症治疗的潜在纳米载体。
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.