类弹性蛋白多肽的生物合成及其药物递送应用

杨兆颖, 张帆, 郭建文, 高卫平

Biosynthesis of Elastin-Like Polypeptides and their applications in drug delivery

Zhaoying YANG, Fan ZHANG, Jianwen GUO, Weiping GAO

图3 ELPs用于延长药物体内循环半衰期。（A）ELP与小分子药物共价偶联，并可由连接子处断裂释放出游离药物；（B）小分子药物与带有靶向序列的ELP偶联，增强了肿瘤细胞对药物的摄取；（C）通过基因工程合成ELP融合蛋白的示意图；（D）NtTNF-VHHELP静脉注射到小鼠后物的药代谢动力学图［34］；（E-F）静脉注射IFN-ELP与IFN的药代谢动力学（E）和肿瘤抑制情况（F）［35］

Fig. 3 ELPs applications in extending half-life of drugs. （A） Chemically conjugated ELP to small molecule drugs by inclusion of an intervening cleavable linker which release the free drug intracellularly after endocytic uptake and accumulation in the acidic， enzyme-rich environment of endosomes and lysosomes； （B）Enhanced cellular uptake of ELP conjugates by functionalization of ELP with cell-penetrating peptides； （C） Schematic of ELP genetically fused to peptide and protein drugs； （D） Pharmacokinetics of NtTNF-VHHELP［34］； （E-F） Pharmacometabolic kinetics （E） and In vivo antitumor effificacy （F） after intravenous injections with IFNα-ELP and IFNα［35］