Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics.
Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics.
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DOI：
10.1021/bm050912z
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发表时间：
2006-04
影响因子：
6.2
通讯作者：
Hong Zhang;Sawitri Mardyani;W. Chan;E. Kumacheva
中科院分区：
文献类型：
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作者：
Hong Zhang;Sawitri Mardyani;W. Chan;E. Kumacheva
我们报告的合理设计的壳聚糖为基础的药物输送系统。壳聚糖衍生物N-[（2-羟基-3-三甲基铵）丙基]壳聚糖氯化物（HTCC）通过三聚磷酸钠（TPP）离子交联形成亚200 nm的微凝胶，该微凝胶对pH变化有响应。当这些微凝胶装载有甲氨蝶呤二钠（MTX）（一种用于癌症治疗的细胞毒性药物）并与靶向生物分子脱辅基转铁蛋白（一种已知通过受体介导的内吞作用进入细胞的蛋白质）缀合时，观察到对永生化HeLa细胞的杀伤增强。在这种细胞内递送方法中，微凝胶暴露于低pH环境，导致壳聚糖溶胀并释放药物。这种合理的药物输送设计可能有助于增强癌症治疗并减少副作用。
We report the rational design of a chitosan-based drug delivery system. The chitosan derivative N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) was ionically cross-linked by sodium tripolyphosphate (TPP) to form sub-200-nm microgels that are responsive to pH changes. When these microgels were loaded with methotrexate disodium (MTX), a cytotoxic drug for cancer treatment, and conjugated to the targeting biomolecule apo-transferrin, a protein known to enter cells via receptor-mediated endocytosis, enhanced killing of immortalized HeLa cells was observed. In this intracellular delivery method, the microgel was exposed to low-pH environments that caused the chitosan to swell and release the drug. This rational drug delivery design may be useful in enhancing cancer therapy and reducing side effects.