National Center for Nanoscience and Technology of China, Beijing, China.
Biomaterials. 2010 Oct;31(28):7364-75. doi: 10.1016/j.biomaterials.2010.06.012.
In this investigation, we have designed and synthesized an amphiphilic co-polymer with hyper-branched poly(amine-ester) and polylactide (HPAE-co-PLA) to generate nanoparticles (NPs). These have been used to encapsulate a highly active hydrophobic anti-tumor agent, 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (Bp4eT). Encapsulation in NPs was done in an effort to increase the anti-tumor activity of this agent by facilitating its delivery to tumor cells. We have also examined and optimized the formulation parameters of the NPs that alter their drug-loading capacity and their physical, chemical and biological properties. The resulting NPs exhibited high Bp4eT-loading capacity and substantial stability in aqueous solution. In vitro drug release studies demonstrated a controlled drug release profile with increased release at acidic pH. Anti-tumor proliferation assays showed that both free drug and drug-encapsulated NPs markedly inhibited tumor cell proliferation in a time- and concentration-dependent manner. Direct microscopic observation revealed that the fluorescent NPs were taken up by cells and localized, in part, in organelles consistent with lysosomes. These results demonstrate a feasible application of the amphiphilic hyper-branched co-polymer, HPAE-co-PLA, as nanocarriers for intracellular delivery of potent anti-tumor agents.
在这项研究中，我们设计并合成了一种具有超支化聚（胺-酯）和聚乳酸（HPAE-co-PLA）的两亲共聚物，以生成纳米颗粒（NPs）。这些纳米颗粒被用来包裹一种高度活跃的疏水性抗肿瘤剂，2-苯甲酰基吡啶 4-乙基-3-硫代缩氨基脲（Bp4eT）。将其包裹在纳米颗粒中是为了通过促进其递送到肿瘤细胞来提高该药物的抗肿瘤活性。我们还检查和优化了改变其载药能力以及物理、化学和生物学性质的纳米颗粒制剂参数。所得的纳米颗粒表现出高的 Bp4eT 载药能力和在水溶液中的显著稳定性。体外药物释放研究表明，在酸性 pH 值下，药物释放呈可控释放模式，释放量增加。抗肿瘤增殖试验表明，游离药物和载药纳米颗粒都能显著地以时间和浓度依赖的方式抑制肿瘤细胞增殖。直接显微镜观察表明，荧光纳米颗粒被细胞摄取，并部分定位于与溶酶体一致的细胞器中。这些结果表明，两亲性超支化共聚物 HPAE-co-PLA 作为有效的抗肿瘤药物的细胞内递药载体具有一定的应用前景。
