Mineart Kenneth P, Venkataraman Shrinivas, Yang Yi Yan, Hedrick James L, Prabhu Vivek M
Materials Science and Engineering Division, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, United States.
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
Macromolecules. 2018 Apr 24;51(8):3184-3192. doi: 10.1021/acs.macromol.8b00361. Epub 2018 Apr 12.
Next-generation liposome systems for anticancer and therapeutic delivery require the precise insertion of stabilizing polymers and targeting ligands. Many of these functional macromolecules may be lost to micellization as a competing self-assembly landscape. Here, hybrid stealth liposomes, which utilize novel cholesteryl-functionalized block copolymers as the molecular stabilizer, are explored as a scalable platform to address this limitation. The employed block copolymers offer resistance to micellization through multiple liposome insertion moieties per molecule. A combination of thermodynamic and structural investigations for a series of hybrid stealth liposome systems suggests that a critical number of cholesteryl moieties per molecule defines whether the copolymer will or will not insert into the liposome bilayer. Colloidal stability of formed hybrid stealth liposomes further corroborates the critical copolymer architecture value.
用于抗癌和治疗递送的下一代脂质体系统需要精确插入稳定聚合物和靶向配体。由于存在竞争性的自组装情况,许多这些功能性大分子可能会因形成胶束而损失。在这里,探索了利用新型胆固醇功能化嵌段共聚物作为分子稳定剂的混合隐形脂质体,作为解决这一限制的可扩展平台。所采用的嵌段共聚物通过每个分子中的多个脂质体插入部分提供抗胶束化能力。对一系列混合隐形脂质体系统进行的热力学和结构研究表明,每个分子中胆固醇部分的临界数量决定了共聚物是否会插入脂质体双层。形成的混合隐形脂质体的胶体稳定性进一步证实了关键共聚物结构的价值。