Co-delivery of TRAIL and paclitaxel by fibronectin-targeting liposomal nanodisk for effective lung melanoma metastasis treatment  

作　　者：Shiqi Huang Lang Deng Hanming Zhang Luyao Wang Yicong Zhang Qing Lin Tao Gong Xun Sun Zhirong Zhang Ling Zhang 

机构地区：[1]Key Laboratory of Drug Targeting and Drug Delivery Systems,Ministry of Education,West China School of Pharmacy,College of Polymer Science and Engineering,Sichuan University,Chengdu 610041,China

出　　处：《Nano Research》2022年第1期728-737,共10页纳米研究（英文版）

基　　金：supported by the Regional Innovation and Development Joint Fund(No.U20A20441);the National Science Fund for Excellent Young Scholars(No.82022070).

摘　　要：Melanoma is a highly aggressive cancer which often forms metastatic tumors in the lung,leading to sharply reduced patients'survival rate.Effectively treating these tumors thus could improve late stage melanoma with lung metastasis.In this study,we fabricated a Cys-Arg-Glu-Lys-Ala with N-methylated Glu(CR(NMe)EKA)decorated disk shaped nano vehicle to co-deliver tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)and paclitaxel(PTX)to lung melanoma tumor sites(TRAIL-[ND-PTX]^(CR(NMe)EKA)).These nanodisks displayed better tumor-targeting and penetration capability than spherical nanoparticles,while the fibronectin-targeting CR(NMe)EKA motif also increased the tumor accumulation of loaded drugs.The combined usage of TRAIL and PTX both killed tumor cells and reduced local nutrition supply,leading to stronger overall anti-tumor effect.This TRAIL-[ND-PTX]^(CR(NMe)EKA)system performed remarkably better than free paclitaxel and also significantly elongated survival rate of melanoma lung metastasis bearing mice,without displaying significant toxicity.Hence,this designing strategy and the fabricated nanoplatform possess potential for further development.

关 键 词：NANODISKS Cys-Arg-Glu-Lys-Ala with N-methylated Glu(CR(NMe)EKA) tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) lung melanoma metastasis tumor-targeting 

分 类 号：R739.5[医药卫生—肿瘤] R318[医药卫生—临床医学]