Park Ju-Hwan, Cho Hyun-Jong, Kim Dae-Duk
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul.
College of Pharmacy, Kangwon National University, Chuncheon, Gangwon, Republic of Korea.
Int J Nanomedicine. 2017 Oct 11;12:7453-7467. doi: 10.2147/IJN.S147668. eCollection 2017.
Poly((D,L)lactic-glycolic)acid-star glucose (PLGA-Glc) polymer-based nanoparticles (NPs) were fabricated for tumor-targeted delivery of docetaxel (DCT). NPs with an approximate mean diameter of 241 nm, narrow size distribution, negative zeta potential, and spherical shape were prepared. A sustained drug release pattern from the developed NPs was observed for 13 days. Moreover, drug release from PLGA-Glc NPs at acidic pH (endocytic compartments and tumor regions) was significantly improved compared with that observed at physiological pH (normal tissues and organs). DCT-loaded PLGA-Glc NPs (DCT/PLGA-Glc NPs) exhibited an enhanced antiproliferation efficiency rather than DCT-loaded PLGA NPs (DCT/PLGA NPs) in Hep-2 cells, which can be regarded as glucose transporters (GLUTs)-positive cells, at ≥50 ng/mL DCT concentration range. Under glucose-deprived (hypoglycemic) conditions, the cellular uptake efficiency of the PLGA-Glc NPs was higher in Hep-2 cells compared to that observed in PLGA NPs. Cy5.5-loaded NPs were prepared and injected into a Hep-2 tumor-xenografted mouse model for in vivo near-infrared fluorescence imaging. The PLGA-Glc NPs group exhibited higher fluorescence intensity in the tumor region than the PLGA NPs group. These results imply that the PLGA-Glc NPs have active tumor targeting abilities based on interactions with GLUTs and the hypoglycemic conditions in the tumor region. Therefore, the developed PLGA-Glc NPs may represent a promising tumor-targeted delivery system for anticancer drugs.
制备了聚（（D，L）乳酸-乙醇酸）-星型葡萄糖（PLGA-Glc）聚合物基纳米颗粒（NPs）用于多西他赛（DCT）的肿瘤靶向递送。制备出了平均直径约为241 nm、粒径分布窄、ζ电位为负且呈球形的纳米颗粒。观察到所制备的纳米颗粒呈现持续13天的药物释放模式。此外，与生理pH值（正常组织和器官）下相比，PLGA-Glc纳米颗粒在酸性pH值（内吞小室和肿瘤区域）下的药物释放显著改善。在≥50 ng/mL DCT浓度范围内，载有DCT的PLGA-Glc纳米颗粒（DCT/PLGA-Glc NPs）在Hep-2细胞中表现出比载有DCT的PLGA纳米颗粒（DCT/PLGA NPs）更高的抗增殖效率，Hep-2细胞可被视为葡萄糖转运蛋白（GLUTs）阳性细胞。在葡萄糖缺乏（低血糖）条件下，Hep-2细胞中PLGA-Glc纳米颗粒的细胞摄取效率高于PLGA纳米颗粒。制备了载有Cy5.5的纳米颗粒并将其注射到Hep-2肿瘤异种移植小鼠模型中进行体内近红外荧光成像。PLGA-Glc纳米颗粒组在肿瘤区域的荧光强度高于PLGA纳米颗粒组。这些结果表明，基于与GLUTs的相互作用以及肿瘤区域的低血糖条件，PLGA-Glc纳米颗粒具有主动肿瘤靶向能力。因此，所开发的PLGA-Glc纳米颗粒可能代表一种有前景的抗癌药物肿瘤靶向递送系统。
