title: Chitosan cross-linked docetaxel loaded EGF receptor targeted nanoparticles for lung cancer cells.
abstract: Lung cancer, associated with the up-regulated epidermal growth factor receptor (EGFR) led to the development of EGFR targeted anticancer therapeutics. The biopolymeric nanoparticles form an outstanding system for the targeted delivery of therapeutic agents. The present work evaluated the in vitro effects of chitosan cross-linked γ-poly(glutamic acid) (γ-PGA) nanoparticles (Nps) loaded with docetaxel (DTXL) and decorated with Cetuximab (CET), targeted to EGFR over-expressing non-small-cell-lung-cancer (NSCLC) cells (A549). CET-DTXL-γ-PGA Nps was prepared by ionic gelation and CET conjugation via EDC/NHS chemistry. EGFR specificity of targeted Nps was confirmed by the higher uptake rates of EGFR +ve A549 cells compared to that of EGFR -ve cells (NIH3T3). The cytotoxicity of Nps quantified using cell based (MTT/LDH) and flowcytometry (Cell-cycle analysis, Annexin V/PI and JC-1) assays showed superior antiproliferative activity of CET-DTXL-γ-PGA Nps over DTXL-γ-PGA Nps. The A549 cells treated with CET-DTXL-γ-PGA NPs underwent a G2/M phase cell cycle arrest followed by reduction in mitochondrial membrane potential of A549 cells, inducing apoptosis and necrosis resulting in enhanced cancer cell death. CET-DTXL-γ-PGA Nps exhibited enhanced cellular internalization and therapeutic activity, by actively targeting EGFR on NSCLC cells and hence could be an effective alternative to non-specific, conventional chemotherapy by increasing its efficiency by many folds.
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
authors.forename: S
authors.initials: S
authors.lastname: Maya
authors.affiliation: IINFACTS, Department of Pharmaceutical Sciences, Instituto Superior de Ciências da Saúde, CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal; INEB, Institute of Biomedical Engineering, University of Porto, Rua do Campo Alegre, Porto, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
authors.forename: Vinoth-Kumar
authors.initials: VK
authors.lastname: Lakshmanan
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
authors.forename: Deepthy
authors.initials: D
authors.lastname: Menon
authors.affiliation: IINFACTS, Department of Pharmaceutical Sciences, Instituto Superior de Ciências da Saúde, CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal.
authors.forename: Vitor
authors.initials: V
authors.lastname: Seabra
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India. Electronic address: rjayakumar@aims.amrita.edu.
authors.forename: R
authors.initials: R
authors.lastname: Jayakumar
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D000068818:Cetuximab; D048271:Chitosan / Q000737:chemistry*; D000077143:Docetaxel; D066246:ErbB Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D043823:Taxoids; C511775:poly(gamma-glutamic acid); D000077143:Docetaxel; D011099:Polyglutamic Acid; D048271:Chitosan; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: Cetuximab; Chitosan; Epidermal growth factor receptor; Poly(γ-glutamic acid) nanoparticles; Targeted nanoparticles