The delivery of N-myc downstream-regulated gene 2(NDRG2)self-amplifying mRNA via modified lipid nanoparticles as a potential treatment for drug-resistant and metastatic cancers  

作　　者：Sandra E.Reznik Amit K.Tiwari Vivek Chavda Charles R.Ashby Jr. 

机构地区：[1]Department of Pharmaceutical Sciences,College of Pharmacy and Health Sciences,St.John’s University,Queens,USA [2]Departments of Pathology and Obstetrics and Gynecology and Women’s Health,Montefiore Medical Center/Albert Einstein College of Medicine,Bronx,USA [3]Department of Pharmaceutical Sciences,College of Pharmacy University of Arkansas for Medical Sciences Little Rock,USA [4]Department of Pharmaceutics and Pharmaceutical Technology L.M.College of Pharmacy,Ahmedabad,India [5]Department of Pharmaceutical Sciences,College of Pharmacy and Health Sciences,St.John’s University,Queens,NY 11439,USA

出　　处：《Medical Review》2024年第3期235-238,共4页医学评论（英文）

摘　　要：The protein,N-myc downstream-regulated gene 2(NDRG2),a tumor suppressor,is significantly decreased or absent in many types of cancer.There is a significant negative correlation between the levels of NDRG2 and the development and progression of cancer tumor recurrence and tumor invasion,in different cancers.In contrast,the in vitro and in vivo overexpression of the NDRG2 protein decreases the proliferation,growth,adhesion and migration of many types of cancer cells.The in vitro overexpression of NDRG2 increases the efficacy of certain anticancer drugs in specific types of cancer cells.We hypothesize that the delivery of the mRNA of the NDRG2 protein,encapsulated by lipid nanoparticles,could represent a potential treatment of metastatic and drug-resistant cancers.This would be accomplished using a self-amplifying mRNA that encodes the NDRG2 protein and an RNA-dependent-RNA polymerase,obtained from an in vitrotranscribed(IVT)mRNA.The IVT mRNA would be encapsulated in a lipid nanoformulation.The efficacy of the nanoformulation would be determined in cultured cancer cells and if the results are positive,nude mice transplanted with either drug-resistant or metastatic drug-resistant cancer cells,would be treated with the nanoformulation and monitored for efficacy and adverse effects.If the appropriate preclinical studies indicate this formulation is efficacious and safe,it is possible it could be evaluated in clinical trials.

关 键 词：N-myc downstream-regulated gene 2(NDRG2) cancer self-amplifying mRNA nanoparticle 

分 类 号：R73-37[医药卫生—肿瘤]