Barz Matthias, Luxenhofer Robert, Zentel Rudolf, Kabanov Alexander V
Institute of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55099 Mainz, Germany.
Biomaterials. 2009 Oct;30(29):5682-90. doi: 10.1016/j.biomaterials.2009.06.058. Epub 2009 Jul 23.
A series of well-defined, fluorescently labelled homopolymers, random and block copolymers based on N-(2-hydroxypropyl)-methacrylamide were prepared by reversible addition-fragmentation chain transfer polymerization (RAFT polymerization). The polydispersity indexes for all polymers were in the range of 1.2-1.3 and the number average of the molar mass (M(n)) for each polymer was set to be in the range of 15-30 kDa. The cellular uptake of these polymers was investigated in the human multi-drug resistant breast adenocarcinoma cell line MCF7/ADR. The uptake greatly depended on the polymer molecular mass and structure. Specifically, smaller polymers (approx. 15 kDa) were taken up by the cells at much lower concentrations than larger polymers (approx. 30 kDa). Furthermore, for polymers of the same molar mass, the random copolymers were more easily internalized in cells than block copolymers or homopolymers. This is attributed to the fact that random copolymers form micelle-like aggregates by intra- and interchain interactions, which are smaller and less stable than the block copolymer structures in which the hydrophobic domain is buried and thus prevented from unspecific interaction with the cell membrane. Our findings underline the need for highly defined polymeric carriers and excipients for future applications in the field of nanomedicine.
通过可逆加成-断裂链转移聚合（RAFT聚合）制备了一系列基于N-（2-羟丙基）-甲基丙烯酰胺的结构明确、荧光标记的均聚物、无规共聚物和嵌段共聚物。所有聚合物的多分散指数在1.2 - 1.3范围内，每种聚合物的数均摩尔质量（M(n)）设定在15 - 30 kDa范围内。在人多药耐药性乳腺腺癌细胞系MCF7/ADR中研究了这些聚合物的细胞摄取情况。摄取情况很大程度上取决于聚合物的分子量和结构。具体而言，较小的聚合物（约15 kDa）在比大聚合物（约30 kDa）低得多的浓度下被细胞摄取。此外，对于相同摩尔质量的聚合物，无规共聚物比嵌段共聚物或均聚物更容易被细胞内化。这归因于无规共聚物通过链内和链间相互作用形成类似胶束的聚集体，其比疏水域被掩埋从而防止与细胞膜发生非特异性相互作用的嵌段共聚物结构更小且更不稳定。我们的研究结果强调了在纳米医学领域未来应用中对高度明确的聚合物载体和赋形剂的需求。
