RAFT聚合诱导自组装制备不同嵌段序列氧化响应性聚合物囊泡

Synthesis of Oxidation Responsive Vesicles with Different Block Sequences via RAFT Polymerization-induced Self-assembly

以聚N,N-二甲基丙烯酰胺(PDMA)为大分子链转移剂(macro-CTA),双丙酮丙烯酰胺(DAAM)和N-丙烯酰硫吗啉(NAT)为单体,在水和二氧六环的混合溶剂中,通过聚合诱导自组装(PISA)制备了3种不同嵌段序列的聚合物纳米颗粒,分别为PDMA-PNAT-PDAAM,PDMA-PDAAM-PNAT以及PDMA-P(NAT-co-DAAM).核磁共振氢谱(1H-NMR)表明单体转化率在5 h内接近100%.通过凝胶渗透色谱(GPC)对聚合物相对分子量及分子量分布进行了表征.通过透射电子显微镜(TEM)研究了嵌段共聚物纳米颗粒的形貌转化过程以及3种聚合物囊泡在双氧水溶液中的氧化响应行为.这种具有氧化响应性的聚合物囊泡有望为药物输送和控制释放提供合适的载体.

Block copolymer(BCP) nanoparticles with three different block sequences, PDMA-PNAT-PDAAM(M-N-D), PDMA-PDAAM-PNAT(M-D-N) and PDMA-P(NAT-co-DAAM)(M-[N-co-D]), are prepared via polymerization-induced self-assembly(PISA). Soluble N-acryloyloxy thiomorpholine(NAT) and diacetone acrylamide(DAAM) are used as monomers to form insoluble core blocks in water, while PDMA35 bearing a trithiocarbonate is utilized as stabilizer and macromolecular chain transfer agent(macro-CTA) to render a RAFT control. Specifically, M-[N-co-D] nano-objects are synthesized via direct RAFT dispersion copolymerization of NAT and DAAM at 70 ℃ employing PDMA35 macro-CTA. To produce M-N-D and M-D-N triblock copolymers,PDMA-PNAT(M-N) and PDMA-PDAAM(M-D) nano-objects are prepared via RAFT dispersion PISA syntheses of NAT and DAAM respectively utilizing PDMA35 macro-CTA and then used for seeded dispersion polymerization of DAAM and NAT respectively without intermediate postpolymerization purification. The thioether moiety in NAT can be oxidized by reactive oxygen species(ROS) into a hydrophilic sulfoxide.Therefore, in the precense of hydrogen peroxide(H2O2), oxidation-responsive morphological degradation of these nano-objects occurs due to the increasing hydrophilicity of NAT units. Given the poor control over polymerization of NAT in pure water, 1,4-dioxane is used as a cosolvent to the PNAT block. So the PISA syntheses are conducted in water/1,4-dioxane(9/1, V/V) mixture to achieve a good control over the molecular weight and narrow distribution. 1 H-NMR spectra indicate that quantitative monomer conversions(> 99%) are achieved within 5 h.Differential scanning calorimeter(DLS) and transmission electron microscopy(TEM) are used to characterize final morphologies of PISA-generated nano-objects and morphological evolution of nano-objects in the presence of H2O2(10 mol/L). These aqueous sequence-controlled PISA formulations are expected to provide responsive nanoparticles with tunable kinetics due to the response-dependent morphological transitions, which may be potentially used as carriers for drug delivery and controlled release.