Small-Sized and Robust Chimaeric Lipopepsomes: A Simple and Functional Platform with High Protein Loading for Targeted Intracellular Delivery of Protein Toxin In Vivo

How to chaperone protein drugs into target tumor cells in vivo is a big challenge. Here, we report on small-sized and robust chimaeric vesicles (lipopepsomes) constructed with asymmetric poly(ethylene glycol)-b-poly(α-aminopalmitic acid)-b-poly(L-aspartic acid) triblock copolypeptide as a simple and functional platform for high loading and targeted intracellular delivery of saporin, a protein toxin, in vivo. Cyclic RGD peptidedecorated chimaeric lipopepsomes (cRGD-CLP) following loading 2.0−9.4 wt % of model protein FITC-labeled cytochrome C showed a small hydrodynamic size of 81−86 nm, enhanced internalization by αvβ3-overexpressing A549 lung tumor cells, as well as remarkable accumulation of 7.73% ID/g in the cancerous lung in mice. Saporin-loaded cRGD-CLP displayed a low halfmaximal inhibitory concentration of 16.3 nM to A549 cancer cells. Intriguingly, saporin-loaded cRGD-CLP at 16.7 nmol saporin equiv/kg showed a high potency in treating orthotopically xenografted A549 lung tumors, suppressed tumor progression, and remarkably improved survival rate. These chimaeric lipopepsomes provide a versatile and potential means for targeted protein therapy of various malignancies.

M. Qiu, Z.Q. Zhang, Y.H. Wei, H.L. Sun, F.H. Meng, C. Deng*, and Z.Y. Zhong*, Small-Sized and Robust Chimaeric Lipopepsomes: A Simple and Functional Platform with High Protein Loading for Targeted Intracellular Delivery of Protein Toxin In Vivo, Chem. Mater. 2018, 30, 6831-6838.