Silk-elastinlike protein polymers (SELPs) self-assemble into nanostructures when designed with appropriate silk-to-elastin ratios. Here, we investigate the effect of insertion of a matrix metalloproteinase-responsive peptide sequence, GPQGIFGQ, into various locations within the SELP backbone on supramolecular self-assembly. Insertion of the hydrophilic, enzyme-degradable sequence into the elastin repeats allows the formation of dilution-stable nanostructures, while insertion into the hydrophobic silk motifs inhibited self-assembly. The SELP assemblies retained their lower critical solution temperature (LCST) thermal response, allowing up to eightfold volumetric changes due to temperature-induced size change. A model hydrophobic drug was incorporated into SELP nanoassemblies utilising a combination of precipitation, incubation and tangential flow filtration. While the nanoconstructs degraded in response to MMP activity, drug release kinetics was independent of MMP concentration. Drug release modelling suggests that release is driven by rates of water penetration into the SELP nanostructures and drug dissolution. In vitro testing revealed that SELP nanoassemblies reduced the immunotoxic and haemolytic side effects of doxorubicin in human blood while maintaining its cytotoxic activity.

丝弹性蛋白样蛋白质聚合物 (SELP) 在设计适当的丝与弹性蛋白比率时自组装成纳米结构。在这里，我们研究了将基质金属蛋白酶响应肽序列 GPQGIFGQ 插入 SELP 主链内的不同位置对超分子自组装的影响。将亲水性、酶可降解序列插入弹性蛋白重复序列​​允许形成稀释稳定的纳米结构，而插入疏水性丝基序会抑制自组装。SELP 组件保留了其较低的临界溶液温度 (LCST) 热响应，允许由于温度引起的尺寸变化而导致的体积变化高达八倍。利用沉淀、孵化和切向流过滤。虽然纳米结构响应 MMP 活性而降解，但药物释放动力学与 MMP 浓度无关。药物释放模型表明释放是由水渗透到 SELP 纳米结构和药物溶出的速率驱动的。体外测试表明，SELP 纳米组件降低了阿霉素在人血液中的免疫毒性和溶血副作用，同时保持其细胞毒活性。