title: Captopril-polyethyleneimine conjugate modified gold nanoparticles for co-delivery of drug and gene in anti-angiogenesis breast cancer therapy.
abstract: Captopril-polyethyleneimine (CP) containing low molecular weight polyethyleneimine and anti-angiogenesis drug captopril conjugated via an amide bond was fabricated to modify gold nanoparticles and complex with siRNA to construct siRNA/CP/GNP complexes for the co-delivery of drug and siRNA in anti-angiogenesis breast cancer therapy. The self-assembled siRNA/CP/GNP complexes exhibited desirable and homogenous particle size, reasonable positive charges and condensation ability, and effective gene-silencing property in vitro. In addition, siRNA/CP/GNP complexes co-delivering captopril and siRNA achieved combined angiogenesis suppression by more effectively downregulating the expression of vascular endothelial growth factor mRNA and protein via different pathways in vitro, as compared to mono-delivery systems. In vivo investigation on nude mice bearing MDA-MB435 tumor xenografts revealed that siRNA/CP/GNP complexes possessed satisfying tumor homing ability and strong antitumor activity. These findings suggested that siRNA/CP/GNP complexes could be an ideal system for simultaneous transfer of drug and siRNA, which might be a new promising strategy for effective breast cancer therapy.
authors.affiliation: a Department of Pathology , The First Affiliated Hospital of Shantou University Medical College , Shantou 515041 , China.
authors.forename: Manhong
authors.initials: M
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Huang
authors.forename: Xizhi
authors.initials: X
authors.lastname: Lu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002216:Captopril / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D020868:Gene Silencing; D017612:Gold Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D053768:Metal Nanoparticles / Q000737:chemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011094:Polyethyleneimine / Q000737:chemistry / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D000067492:RNAi Therapeutics / Q000379:methods*; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D004337:Drug Carriers; D017612:Gold Compounds; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D011094:Polyethyleneimine; D002216:Captopril
keywords: anti-angiogenesis; breast cancer; captopril; gold nanoparticles; siRNA