Formation of Unimer Nanoparticles by Controlling the Self-Association of Hydrophobically Modified Poly(amino acid)s
Formation of Unimer Nanoparticles by Controlling the Self-Association of Hydrophobically Modified Poly(amino acid)s
复制标题
DOI：
10.1021/la205093j
复制
发表时间：
2012-03-20
期刊：
影响因子：
3.9
通讯作者：
Akashi, Mitsuru
中科院分区：
文献类型：
--
作者：
Akagi, Takami;Piyapakorn, Phassamon;Akashi, Mitsuru
两亲性嵌段或接枝共聚物已被证明在选择性溶剂中形成各种自组装纳米/微米结构。研究了以聚γ-谷氨酸（gamma-PGA）为亲水链段，L-苯丙氨酸（Phe）为疏水链段的生物可降解接枝共聚物在水溶液中的自缔合行为。研究了γ-PGA-Phe（γ-PGA-Phe）共聚物在水溶液中的缔合行为和单聚体纳米粒子的形成，重点考察了Phe接枝度对γ-PGA-Phe共聚物内和共聚物间缔合的影响。在一个颗粒的γ-PGA-Phe的聚合物聚集体（N-agg）的粒径和数量取决于Phe接枝程度。具有12、27、35或42%Phe接枝的γ-PGA-Phe（γ-PGA-Phe-12、-27、-35或-42）的尺寸为约8-14 nm，并且N-agg为约1，支持PBS中存在单分子接枝共聚物。芘荧光数据表明，γ-PGA-Phe-35和-42具有由Phe连接到γ-PGA的聚合物内缔合形成的疏水结构域。这些结果表明，Phe的接枝程度对γ-PGA-Phe的缔合行为有重要影响，γ-PGA-Phe-35和-42可以形成单聚体纳米粒。此外，当将溶解在DMSO中的γ-PGA-Phe-42加入到不同浓度的NaCl溶液中时，可以通过在颗粒形成期间改变NaCl浓度来容易地控制颗粒的尺寸和N-agg。这些结果表明，可生物降解的γ-PGA-Phe可用于制造非常小的纳米颗粒。预计γ-PGA-Phe纳米颗粒，包括单聚体颗粒，将具有作为用于药物和生物医学应用的多功能载体的巨大潜力，例如药物和疫苗递送系统。
Amphiphilic block or graft copolymers have been demonstrated to form a variety of self-assembled nano/microstructures in selective solvents. In this study, the self-association behavior of biodegradable graft copolymers composed of poly(gamma-glutamic acid) (gamma-PGA) as the hydrophilic segment and L-phenylalanine (Phe) as the hydrophobic segment in aqueous solution was investigated. The association behavior and unimer nanoparticle formation of these gamma-PGA-graft-Phe (gamma-PGA-Phe) copolymers in aqueous solution were characterized with a focus on the effect of the Phe grafting degree on the intra-and interpolymer association of gamma-PGA-Phe. The particle size and number of polymer aggregates (N-agg) in one particle of the gamma-PGA-Phe depended on the Phe grafting degree. The size of gamma-PGA-Phe with 12, 27, 35, or 42% Phe grafting (gamma-PGA-Phe-12, -27, -35, or -42) was about 8-14 nm and the N-agg was about 1, supporting the presence of a unimolecular graft copolymer in PBS. The pyrene fluorescence data indicated that gamma-PGA-Phe-35 and -42 have hydrophobic domains formed by the intrapolymer association of Phe attached to gamma-PGA. These results suggest that the Phe grafting degree is critical to the association behavior of gamma-PGA-Phe and that gamma-PGA-Phe-35 and -42 could form unimer nanoparticles. Moreover, when gamma-PGA-Phe-42 dissolved in DMSO was added to various concentrations of NaCl solution, the particle size and N-agg could be easily controlled by changing the NaCl concentration during the formation of the particles. These results suggest that biodegradable gamma-PGA-Phe is useful for the fabrication of very small nanoparticles. It is expected that gamma-PGA-Phe nanoparticles, including unimer particles, will have great potential as multifunctional carriers for pharmaceutical and biomedical applications, such as drug and vaccine delivery systems.