title: Ligand-targeted bacterial minicells: Futuristic nano-sized drug delivery system for the efficient and cost effective delivery of shRNA to cancer cells.
abstract: In this study, shRNA against VEGFA was packaged in bacterial minicells and surface of minicells was modified with folic acid. Analysis of cellular internalization revealed that folic acid conjugated minicells internalized through receptor mediated endocytosis in folate and PSMA receptor positive KB and LNCaP cells, respectively. In contrast, A549 (folate receptor negative) cells showed minute internalization. In vitro delivery ofFAminicellsVEGFAsignificantly reduced the expression of VEGFA mRNA in KB and LNCaP cells whereas expression of VEGFA remained unaltered in A549 cells.FAminicellsVEGFAsignificantly reduced tumor volume in mice bearing KB and LNCaP xenograft. On contrary, gradual increase in the tumor volume was recorded in A549 xenograft.FAminicellsVEGFAsignificantly silenced the VEGFA mRNA in KB and LNCaP xenograft. Expression of VEGFA remained same inFAminicellsVEGFAdelivered A549 xenograft. In vivo biodistribution study showed that majority ofFAminicellsVEGFAwere localized in the tumor followed by intravenous administration.
authors.affiliation: Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Sarkhej-Gandhinagar Highway, Thaltej, Ahmedabad, Gujarat, India; Faculty of Science, NIRMA University, Sarkhej-Gandhinagar Highway, Gota, Ahmedabad, Gujarat, India. Electronic address: mehjiv@rediffmail.com.
authors.forename: Mehul
authors.initials: M
authors.lastname: Jivrajani
authors.affiliation: Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Sarkhej-Gandhinagar Highway, Thaltej, Ahmedabad, Gujarat, India. Electronic address: manishnivsarkar@gmail.com.
authors.forename: Manish
authors.initials: M
authors.lastname: Nivsarkar
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004705:Endocytosis; D005492:Folic Acid; D064593:Heterografts; D006801:Humans; D051379:Mice; D036103:Nanotechnology / Q000379:methods; D034741:RNA, Small Interfering; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A
chemical_list: D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D005492:Folic Acid
keywords: Bacterial minicells; Cancer; Folate receptor targeted delivery; RNA interference; shRNA delivery