title: Intracellular delivery of peptide cargos using polyhydroxybutyrate based biodegradable nanoparticles: Studies on antitumor efficacy of BCL-2 converting peptide, NuBCP-9.
abstract: Faster biodegradation, immunogenicity and lack of cell penetrative capabilities are hurdles in development of peptidyl drugs for cancer therapy. Polymeric carriers can be used to overcome these problems. The present study is focused on the use of polyhydroxybutyrate as a potential nanovehicle for the delivery of anticancer peptides. PHB (72kDa) was produced by thermal treatment of high molecular weight PHB (300kDa) under melt conditions and then conjugated with PEG (4kDa) by Steglich esterification reaction. Anticancer peptide NuBCP-9 (FSRSLHSLL) encapsulated PHB(72K)-PEG(4K) NPs were prepared by double emulsion solvent evaporation method. PHB(72K)-PEG(4K) NPs showed encapsulation efficiency of 61% and exhibited sustained release of peptide over a period of 26days at physiological pH. NuBCP-9 loaded PHB(72K)-PEG(4K) NPs showed an IC50 value of 2.2μM & 1.6μM in MCF-7 cells in 48h and 72h respectively. Confocal laser microscopy confirmed efficient cellular uptake and induction of apoptosis by peptide loaded NPs in a time dependent manner. In vivo intraperitonial administration of 20mg/kg NuBCP-9/NPs twice a week for three weeks triggered 90% tumor regression in Ehrlich syngeneic mouse model. Our results illustrated the potential of PHB(72K)-PEG(4K) based nanoformulation as a tool for targeting intracellular proteins.
authors: Centre for Biomedical Engineering, Indian Institute of Technology, New Delhi, 110016; All India Institute of Medical sciences, New Delhi 110029, India. Electronic address: s.kapooriitd@gmail.com.
authors: Sumeet
authors: S
authors: Kapoor
authors: Centre for Biomedical Engineering, Indian Institute of Technology, New Delhi, 110016; All India Institute of Medical sciences, New Delhi 110029, India. Electronic address: dikshi.gupta@gmail.com.
authors: Dikishi
authors: D
authors: Gupta
authors: Centre for Biomedical Engineering, Indian Institute of Technology, New Delhi, 110016; All India Institute of Medical sciences, New Delhi 110029, India. Electronic address: manojgautam.iitd@gmail.com.
authors: Manoj
authors: M
authors: Kumar
authors: Centre for Biomedical Engineering, Indian Institute of Technology, New Delhi, 110016; All India Institute of Medical sciences, New Delhi 110029, India. Electronic address: sharmansapna.iitd@gmail.com.
authors: Sapna
authors: S
authors: Sharma
authors: Department of Mechanical Engineering, Indian Institute of Technology, New Delhi,110016, India. Electronic address: amit_108@protonmail.com.
authors: Amit K
authors: AK
authors: Gupta
authors: National Institutes of Health and Family Welfare, New Delhi,110067, India. Electronic address: mm_misro@yahoo.com.
authors: M M
authors: MM
authors: Misro
authors: Centre for Biomedical Engineering, Indian Institute of Technology, New Delhi, 110016; All India Institute of Medical sciences, New Delhi 110029, India. Electronic address: harpal2000@yahoo.com.
authors: Harpal
authors: H
authors: Singh
mesh_terms: D042401:Alcaligenaceae / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006885:Hydroxybutyrates / Q000737:chemistry* / Q000302:isolation & purification; D061986:MCF-7 Cells / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry; D000091402:Prohibitins
chemical_list: D004337:Drug Carriers; D006885:Hydroxybutyrates; D009842:Oligopeptides; C000717328:PHB protein, human; D000091402:Prohibitins; C000590397:phenylalanyl-seryl-arginyl-seryl-leucyl-histidyl-seryl-leucyl-leucine; D011092:Polyethylene Glycols; C000595213:polyethylene glycol 400
keywords: Anticancer peptides; BCL-2 protein; PHB(72K)-PEG(4K); Polymeric nanoparticles