Integrated Combination Treatment Using a “Smart” Chemotherapy and MicroRNA Delivery System Improves Outcomes in an Orthotopic Colorectal Cancer Model
作者单位：Hongqiao International Institute of Medicine Shanghai Tongren Hospital and Department of Pharmacology and Chemical BiologyInstitute of Medical SciencesShanghai Jiao Tong University School of Medicine (SJTU-SM) Department of General SurgeryShanghai Tongren HospitalSJTU-SM Department of PharmacyShanghai University of Medicine and Health Sciences Department of Biomedical EngineeringUniversity at BuffaloState University of New York
会议名称：《首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会》
会议日期：2018年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：miRNA Integrated Combination Treatment Using a Smart Chemotherapy and MicroRNA Delivery System Improves Outcomes in an Orthotopic Colorectal Cancer Model
摘 要：Mesoporous silica nanoparticles(MSN) can load and deliver potentially synergistic anticancer agents such as small molecule cytotoxics(like doxorubicin,DOX) and nucleic acids(like microRNA,miRNA).However,these cargos have different underlying chemical properties so overcoming respective intracellular delivery barriers is a key *** to deliver DOX from MSN frequently employ pH-driven mechanisms that are restricted to the acidic environment of ***,strategies to deliver miRNA make use of approaches that deliberately compromise lysosomal membrane integrity to enable cytosolic delivery of the *** reconcile these two needs(lysosomal delivery of DOX and intracellular delivery of miRNA),a new methodology by weaving polyethylenimine on the MSN surface through disulfide bonds to achieve superior delivery of chemotherapy(DOX) and miRNA therapy(using miRNA-145) is ***,an active targeting strategy based on a peptide ligand with affinity to glucose-regulated protein 78(GRP78),a cell surface protein overexpressed in colorectal carcinoma,is *** active targeting approach results in enhanced synergistic antitumor effect both in vitro and in vivo in an orthotopic murine model of colorectal *** together,this work demonstrates the capability and advantages of smart MSN delivery systems to deliver anticancer cargo appropriately to targeted cancer cells.