Department of Chemical and Materials, University of Alberta, ECERF, Edmonton, Alberta T6G 2G6, Canada.
Langmuir. 2009 Dec 1;25(23):13344-50. doi: 10.1021/la9034276.
We report on the fabrication of core cross-linked (CCL) micelles possessing thermoresponsive and degradable cores and biocompatible coronas cofunctionalized with carbohydrate and biotin moieties. Well-defined poly(2-aminoethylmethacrylamide) (PAEMA) homopolymer was first synthesized in a controlled fashion via the reversible addition-fragmentation chain transfer (RAFT) process. CCL micelles comprising of well-solvated PAEMA coronas and thermoresponsive cores were then obtained in a one-pot manner via RAFT copolymerization of N-isopropylacrylamide (NIPAM) and bis(2-methacryloyloxyethyl) disulfide (DSDMA) difunctional monomers by employing PAEMA as the macro-RAFT agent. In the presence of dithiothreitol (DTT), the obtained CCL micelles can be disintegrated into unimers due to the cleavage of disulfide cross-linkers, whereas deswelling of micellar cores can be achieved via heating above the phase transition temperature of PNIPAM. Thus, the release profiles of this type of nanocarriers are expected to be triggered by temperature and thiols or a combination of both. Furthermore, primary amine residues located within coronas of CCL micelles have been further exploited for surface functionalization with biotin and carbohydrate moieties, rendering them biocompatible and bioactive. The availability of biotin within the coronas of CCL micelles was confirmed by HABA/avidin binding assay and Diffractive Optics Technology (DOT) biosensing instrument. After the micelles were immobilized on the surface of avidin-sensor chip, specific biorecognition of the available biotins and carbohydrate moieties on the CCL micelles was further confirmed. We expect that this novel type of bioactive and potentially biocompatible CCL micelles can be employed as smart nanocarriers for targeted drug delivery and controlled release.
我们报告了核心交联（CCL）胶束的制备，这些胶束具有热响应性和可降解的核心以及共功能化的碳水化合物和生物素部分的生物相容性冠层。首先通过可逆加成-断裂链转移（RAFT）过程以受控方式合成了具有良好定义的聚（2-氨基乙基甲基丙烯酰胺）（PAEMA）均聚物。然后，通过 RAFT 共聚 N-异丙基丙烯酰胺（NIPAM）和双（2-甲基丙烯酰氧基乙基）二硫代琥珀酸酯（DSDMA）双功能单体，以 PAEMA 为大分子 RAFT 试剂，以一锅法获得了包含溶胀良好的 PAEMA 冠层和热响应性核心的 CCL 胶束。在二硫苏糖醇（DTT）的存在下，由于二硫键交联剂的断裂，所得的 CCL 胶束可以分解为单体，而通过加热至 PNIPAM 的相转变温度以上可以实现胶束核心的溶胀。因此，预计这种纳米载体的释放曲线可以通过温度和硫醇或两者的组合来触发。此外，CCL 胶束冠层中的伯胺残基进一步用于用生物素和碳水化合物部分进行表面功能化，从而使它们具有生物相容性和生物活性。通过 HABA/亲和素结合测定和衍射光学技术（DOT）生物传感仪证实了 CCL 胶束冠层中生物素的可用性。胶束固定在亲和素传感器芯片表面后，进一步证实了 CCL 胶束上可用生物素和碳水化合物部分的特异性生物识别。我们期望这种新型的生物活性和潜在的生物相容的 CCL 胶束可以用作智能纳米载体，用于靶向药物输送和控制释放。
