TY - JOUR
T1 - Small-Sized and Robust Chimaeric Lipopepsomes
T2 - A Simple and Functional Platform with High Protein Loading for Targeted Intracellular Delivery of Protein Toxin in Vivo
AU - Qiu, Min
AU - Zhang, Zhenqi
AU - Wei, Yaohua
AU - Sun, Huanli
AU - Meng, Fenghua
AU - Deng, Chao
AU - Zhong, Zhiyuan
N1 - ACS deal
PY - 2018/10/9
Y1 - 2018/10/9
N2 - 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 peptide-decorated 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 half-maximal 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.
AB - 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 peptide-decorated 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 half-maximal 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.
KW - UT-Hybrid-D
UR - http://www.scopus.com/inward/record.url?scp=85053667245&partnerID=8YFLogxK
U2 - 10.1021/acs.chemmater.8b02868
DO - 10.1021/acs.chemmater.8b02868
M3 - Article
AN - SCOPUS:85053667245
VL - 30
SP - 6831
EP - 6838
JO - Chemistry of materials
JF - Chemistry of materials
SN - 0897-4756
IS - 19
ER -