National Engineering Laboratory of Clean Technology of Leather Manufacture, Sichuan University, Chengdu 610065, China.
Biomater Sci. 2015 Mar;3(3):490-9. doi: 10.1039/c4bm00385c. Epub 2014 Dec 22.
In cancer therapy, surface engineering of drug delivery systems plays an essential role in their colloidal stability, biocompatibility and prolonged blood circulation. Inspired by the cell membrane consisting of phospholipids and glycolipids, a zwitterionic phosphorylcholine functionalized chitosan oligosaccharide (PC-CSO) was first synthesized to mimic the hydrophilic head groups of those amphipathic lipids. Then hydrophobic stearic acid (SA) similar to lipid fatty acids was grafted onto PC-CSO to form amphiphilic PC-CSO-SA copolymers. Cell membrane-mimetic micelles with a zwitterionic surface and a hydrophobic SA core were prepared by the self-assembly of PC-CSO-SA copolymers, showing excellent stability under extreme conditions including protein containing media, high salt content or a wide pH range. Doxorubicin (DOX) was successfully entrapped into polymeric micelles through the hydrophobic interaction between DOX and SA segments. After fast internalization by cancer cells, sustained drug release from micelles to the cytoplasm and nucleus was achieved. This result suggests that these biomimetic polymeric micelles may be promising drug delivery systems in cancer therapy.
在癌症治疗中，药物传递系统的表面工程在其胶体稳定性、生物相容性和延长血液循环方面起着至关重要的作用。受由磷脂和糖脂组成的细胞膜的启发，首次合成了两性离子磷酸胆碱功能化壳聚糖寡糖（PC-CSO），以模拟这些两亲脂质的亲水头基。然后，类似于脂质脂肪酸的疏水性硬脂酸（SA）被接枝到 PC-CSO 上，形成两亲性 PC-CSO-SA 共聚物。通过 PC-CSO-SA 共聚物的自组装制备了具有两性离子表面和疏水性 SA 核的细胞膜模拟胶束，在包括含蛋白介质、高盐含量或宽 pH 范围在内的极端条件下表现出优异的稳定性。通过 DOX 与 SA 段之间的疏水相互作用，成功地将阿霉素（DOX）包埋在聚合物胶束中。在癌细胞快速内化后，实现了从胶束到细胞质和细胞核的药物持续释放。这一结果表明，这些仿生聚合物胶束可能是癌症治疗中有前途的药物传递系统。
