title: A spatio-temporal cardiomyocyte targeted vector system for efficient delivery of therapeutic payloads to regress cardiac hypertrophy abating bystander effect.
abstract: Diverse array of therapeutic regimens, drugs or siRNA, are commonly used to regress cardiac hypertrophy, although, bystander effect and lower retention of bioactive molecules significantly reduce their functional clinical efficacy. Carvedilol, a widely used and effective anti-hypertrophic drug, simultaneously blocks β-adrenergic receptors non-specifically in various organs. Likewise, non-specific genome-wide downregulation of p53 expression by specific siRNA efficiently abrogates cardiac hypertrophy but results in extensive tumorigenesis affecting bystander organs. Therefore, delivery of such therapeutics had been a challenge in treating cardiovascular dysfunction. Cardiac tissue engineering was successfully accomplished in this study, by encapsulating such bioactive molecules with a stearic acid modified Carboxymethyl chitosan (CMC) nanopolymer conjugated to a homing peptide for delivery to hypertrophied cardiomyocytes in vivo. The peptide precisely targeted cardiomyocytes while CMC served as the vector mediator to pathological myocardium. Controlled delivery of active therapeutic payloads within cardiomyocytes resulted in effective regression of cardiac hypertrophy. Thus, this novel nano-construct as a spatio-temporal vector would be a potential tool for developing effective therapeutic strategies within cardiac micro-environment via targeted knockdown of causal genes.
authors.affiliation: Department of Zoology, University of Calcutta, 35, B.C. Road, Kolkata 700019, India.
authors.forename: Santanu
authors.initials: S
authors.lastname: Rana
authors.affiliation: Department of Zoology, University of Calcutta, 35, B.C. Road, Kolkata 700019, India.
authors.forename: Kaberi
authors.initials: K
authors.lastname: Datta
authors.affiliation: Centre for Chemical Biology, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India.
authors.forename: Teegala Lakshminarayan
authors.initials: TL
authors.lastname: Reddy
authors.affiliation: Department of Zoology, University of Calcutta, 35, B.C. Road, Kolkata 700019, India.
authors.forename: Emeli
authors.initials: E
authors.lastname: Chatterjee
authors.affiliation: Department of Zoology, University of Calcutta, 35, B.C. Road, Kolkata 700019, India.
authors.forename: Preeta
authors.initials: P
authors.lastname: Sen
authors.affiliation: Centre for Chemical Biology, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India.
authors.forename: Manika
authors.initials: M
authors.lastname: Pal-Bhadra
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.
authors.forename: Utpal
authors.initials: U
authors.lastname: Bhadra
authors.affiliation: Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India.
authors.forename: Arindam
authors.initials: A
authors.lastname: Pramanik
authors.affiliation: Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India.
authors.forename: Panchanan
authors.initials: P
authors.lastname: Pramanik
authors.affiliation: Division of Virology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road Scheme-XM, Beliaghata, Kolkata 700010, India.
authors.forename: Mamta
authors.initials: M
authors.lastname: Chawla-Sarkar
authors.affiliation: Department of Zoology, University of Calcutta, 35, B.C. Road, Kolkata 700019, India. Electronic address: sagartirtha.sarkar@gmail.com.
authors.forename: Sagartirtha
authors.initials: S
authors.lastname: Sarkar
mesh_terms: D000818:Animals; D024201:Bystander Effect; D002227:Carbazoles / Q000008:administration & dosage* / Q000737:chemistry; D006332:Cardiomegaly / Q000188:drug therapy* / Q000235:genetics; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000737:chemistry; D000077261:Carvedilol; D002478:Cells, Cultured; D048271:Chitosan / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D006801:Humans; D032383:Myocytes, Cardiac; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D011412:Propanolamines / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D017208:Rats, Wistar; D013229:Stearic Acids / Q000737:chemistry; D023822:Tissue Engineering; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D002227:Carbazoles; D002316:Cardiotonic Agents; D010455:Peptides; D011412:Propanolamines; D034741:RNA, Small Interfering; D013229:Stearic Acids; D016159:Tumor Suppressor Protein p53; D000077261:Carvedilol; C031183:stearic acid; D048271:Chitosan
keywords: Carboxy methyl chitosan; Cardiac tissue engineering; Cardiomyocyte; Drug delivery; Gene therapy