Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institutet, Retzius väg 8, SE-171 77, Stockholm, Sweden.
Biomacromolecules. 2012 Nov 12;13(11):3814-22. doi: 10.1021/bm301281k. Epub 2012 Oct 12.
Dendrimers and their less well-defined cousins, hyperbranched polymers, are widely investigated as scaffold materials in tissue engineering, as drug delivery agents, and in diagnostic imaging applications. Despite the large interest of using these unique materials as polymer-based nanoparticles in biomedical applications, a clear understanding of the cellular uptake and transport of these polyester-based nanoparticles is still lacking. The objective of this study is to evaluate the cellular uptake profiles and intracellular trafficking of polymer micelles built from the hyperbranched polyester Boltorn, fitted with poly(ethylene glycol) and fluorescent groups in MDA-MB468 breast cancer cells. Results show that the uptake of these nanoparticles correlated positively to both time and concentration, and that the uptake of the nanoparticles was energy dependent. These polyesterbased nanoparticles appear to translocate across cells via clathrin- and macropinocytosis-mediated endocytosis. Observations of the intracellular trafficking of the nanoparticles indicate that particles could be released from early endosomes after being internalized, and the particles exhibit perinuclear localization. The uptake behavior of the nanoparticles was further evaluated in a range of cell lines. These results allow the generation of the knowledge base required to design polyester-based nanocarriers that can be used efficiently and specifically for drug delivery applications and imaging applications.
树枝状大分子及其定义不太明确的表亲——超支化聚合物，被广泛研究作为组织工程中的支架材料、药物传递剂和诊断成像应用。尽管人们对将这些独特的材料作为基于聚合物的纳米粒子用于生物医学应用有着浓厚的兴趣，但对于这些基于聚酯的纳米粒子的细胞摄取和转运机制仍缺乏清晰的认识。本研究旨在评估由超支化聚酯 Boltorn 构建的聚合物胶束的细胞摄取特征和细胞内转运情况，这些胶束上接枝了聚乙二醇和荧光基团，在 MDA-MB468 乳腺癌细胞中进行了研究。结果表明，这些纳米粒子的摄取与时间和浓度呈正相关，并且摄取过程依赖于能量。这些基于聚酯的纳米粒子似乎通过网格蛋白和巨胞饮作用介导的内吞作用跨细胞转运。对纳米粒子的细胞内转运的观察表明，粒子在内化后可以从早期内体中释放出来，并且粒子呈现核周定位。进一步在一系列细胞系中评估了纳米粒子的摄取行为。这些结果为设计基于聚酯的纳米载体提供了所需的知识库，这些载体可以高效且有针对性地用于药物传递应用和成像应用。
