Tumor pH-responsive flower-like micelles of poly(L-lactic acid)-b-poly (ethylene glycol)-b-poly(L-histidine)
Tumor pH-responsive flower-like micelles of poly(L-lactic acid)-b-poly (ethylene glycol)-b-poly(L-histidine)
复制标题
DOI：
10.1016/j.jconrel.2007.08.006
复制
发表时间：
2007-10-18
影响因子：
10.8
通讯作者：
Bae, You Han
中科院分区：
文献类型：
--
作者：
Lee, Eun Seong;Oh, Kyung Taek;Bae, You Han
以聚L-乳酸（PLA; M-n 3 K）-聚乙二醇（PEG; M-n 2K）-聚组氨酸（polyHis; M-n 5 K）为聚合物胶束，构建了肿瘤pH特异性抗癌药物载体。胶束（粒径：类似于80 nm;临界胶束浓度（CMC）：2 μ g/ml），通过将聚合物在二甲基亚砜（DMSO）中的溶液与pH 8.0的水溶液透析形成，假定在核心中具有PLA和聚His嵌段的花状组装体，并将PEG嵌段作为壳。胶束的pH敏感性源于胶束核心的变形，由于电离的polyHis在微酸性pH值。然而，在核心中的pH不敏感的亲脂性PLA块的共存防止胶束的崩解，并引起溶胀/聚集。荧光探针的研究表明，芘保留在胶束中的极性增加，pH值从7.4降低到6.6，表明胶束中的一个更亲水的环境的变化。考虑到胶束的尺寸从pH 7.4时的80 nm增加到pH 6.6时的580 nm，并且胶束溶液的透射率随着pH的降低而增加，胶束没有解离而是溶胀/聚集。有趣的是，随后的芘极性低于pH 6.6的下降表明嵌段共聚物的重新自组装，最有可能形成PLA嵌段核，而聚His嵌段重新定位到表面。因此，PLA-b-PEG-b-polyHis胶束的这些pH依赖性物理变化提供了由pH的小变化（pH 7.2-6.5）触发的从胶束中触发药物释放的机制。(c)2007 Elsevier B. V.保留所有权利。
Polymeric micelles were constructed from poly(L-lactic acid) (PLA; M-n 3K)-b-poly(ethylene glycol) (PEG; M-n 2K)-b-poly(L-histidine) (polyHis; M-n 5K) as a tumor pH-specific anticancer drug carrier. Micelles (particle diameter: similar to 80 nm; critical micelle concentration (CMC): 2 mu g/ml) formed by dialysis of the polymer solution in dimethylsulfoxide (DMSO) against pH 8.0 aqueous solution, are assumed to have a flower-like assembly of PLA and polyHis blocks in the core and PEG block as the shell. The pH-sensitivity of the micelles originates from the deformation of the micellar core due to the ionization of polyHis at a slightly acidic pH. However, the co-presence of pH-insensitive lipophilic PLA block in the core prevented disintegration of the micelles and caused swelling/aggregation. A fluorescence probe study showed that the polarity of pyrene retained in the micelles increased as pH was decreased from 7.4 to 6.6, indicating a change to a more hydrophilic environment in the micelles. Considering that the size increased up to 580 nm at pH 6.6 from 80 nm at pH 7.4 and that the transmittance of micellar solution increased with decreasing pH, the micelles were not dissociated but rather swollen/aggregated. Interestingly, the subsequent decline of pyrene polarity below pH 6.6 suggested re-self-assembly of the block copolymers, most likely forming a PLA block core while polyHis block relocation to the surface. Consequently, these pH-dependent physical changes of the PLA-b-PEG-b-polyHis micelles provide a mechanism for triggered drug release from the micelles triggered by the small change in pH (pH 7.2-6.5). (c) 2007 Elsevier B.V. All rights reserved.