Lee Jeonghun, Tang Yao, Cureño Hernandez Karla E, Kim Sunghoon, Lee Rahmi, Cartwright Zachary, Pochan Darrin J, Herrera-Alonso Margarita
School of Materials Science and Engineering, Colorado State University, Fort Collins, Colorado 80523, United States.
Department of Materials Science and Engineering, University of Delaware, Newark, Delaware 19716, United States.
ACS Appl Mater Interfaces. 2024 Oct 6. doi: 10.1021/acsami.4c10968.
Bottlebrush copolymers are increasingly used for drug delivery and biological imaging applications in part due to the enhanced thermodynamic stability of their self-assemblies. Herein, we discuss the effect of hydrophilic block chemistry on the stability of bottlebrush micelles. Amphiphilic bottlebrushes with zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and nonionic polyethylene glycol (PEG) hydrophilic blocks were synthesized by "grafting from" polymerization and self-assembled into well-defined spherical micelles. Colloidal stability and stability against disassembly were challenged under high concentrations of NaCl, MgSO, sodium dodecyl sulfate, fetal bovine serum, and elevated temperature. While both types of micelles appeared to be stable in many of these conditions, those with a PMPC shell consistently surpassed their PEG analogs. Moreover, when repeatedly subjected to lyophilization/resuspension cycles, PMPC micelles redispersed with no apparent variation in size or dispersity even in the absence of a cryoprotectant; PEG micelles readily aggregated. The observed excellent stability of PMPC micelles is attributed to the low critical micelle concentration of the bottlebrushes as well as to the strong hydration shell caused by ionic solvation of the phosphorylcholine moieties. Zwitterionic micelles were loaded with doxorubicin, and higher loading capacity/efficiency, as well as delayed release, was observed with increasing side-chain length. Finally, hemocompatibility studies of PMPC micelles demonstrated no disruption to the red blood cell membranes. The growing concern regarding the immunogenicity of PEG-based systems propels the search for alternative hydrophilic polymers; in this respect and for their outstanding stability, zwitterionic bottlebrush micelles represent excellent candidates for drug delivery and bioimaging applications.
刷状共聚物因其自组装体具有增强的热力学稳定性，越来越多地用于药物递送和生物成像应用。在此，我们讨论亲水性嵌段化学对刷状胶束稳定性的影响。通过“接枝聚合”合成了具有两性离子聚（2-甲基丙烯酰氧基乙基磷酰胆碱）（PMPC）和非离子聚乙二醇（PEG）亲水性嵌段的两亲性刷状聚合物，并自组装成明确的球形胶束。在高浓度的氯化钠、硫酸镁、十二烷基硫酸钠、胎牛血清以及高温条件下，对胶体稳定性和抗解聚稳定性进行了挑战。虽然在许多这些条件下，两种类型的胶束似乎都很稳定，但具有PMPC外壳的胶束始终优于其PEG类似物。此外，当反复进行冻干/重悬循环时，即使在没有冷冻保护剂的情况下，PMPC胶束也能重新分散，尺寸和分散度没有明显变化；PEG胶束则容易聚集。观察到的PMPC胶束的优异稳定性归因于刷状聚合物的低临界胶束浓度以及磷酰胆碱部分的离子溶剂化所导致的强大水合壳。用阿霉素负载两性离子胶束，随着侧链长度的增加，观察到更高的负载容量/效率以及延迟释放。最后，PMPC胶束的血液相容性研究表明对红细胞膜没有破坏。对基于PEG的系统的免疫原性的日益关注推动了对替代亲水性聚合物的探索；在这方面，两性离子刷状胶束因其出色的稳定性，是药物递送和生物成像应用的优秀候选者。
