DOI: 10.1515/mr-2024-0004
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
Sandra E.Reznik1
Amit K.Tiwari2
Vivek Chavda3
Charles R.Ashby Jr.4
1.Department of Pharmaceutical Sciences,College of Pharmacy and Health Sciences,St.John's University,Queens,USA;Departments of Pathology and Obstetrics and Gynecology and Women's Health,Montefiore Medical Center/Albert Einstein College of Medicine,Bronx,USA2.Department of Pharmaceutical Sciences,College of Pharmacy University of Arkansas for Medical Sciences Little Rock,USA3.Department of Pharmaceutics and Pharmaceutical Technology L.M.College of Pharmacy,Ahmedabad,India4.Department of Pharmaceutical Sciences,College of Pharmacy and Health Sciences,St.John's University,Queens,NY 11439,USA
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 nega-tive 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 1VT 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 nano-formulation and monitored for efficacy and adverse effects.If the appropriate preclinical studies indicate this formula-tion is efficacious and safe,it is possible it could be evaluated in clinical trials.
机标关键词：modifiedndrg2mrnagenecancersdeliverydownstreamdrug-resistant
论文发表日期：2024-06-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：4( 235-238 )
英文信息