title: Computational and mechanistic studies on the effect of galactoxyloglucan: Imatinib nanoconjugate in imatinib resistant K562 cells.
abstract: Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects. This study involved in the synthesis of PST-Imatinib nanoconjugates with appreciable drug payload and excellent cytotoxicity against drug-resistant chronic myelogenous leukemia cell line (K562) in comparison with free drug. The use of bioinformatics tool revealed better binding affinity for the drug-polysaccharide complex than the drug alone with three proteins: 3QX3 (Topoisomerase), 1M17 (EGFR tyrosine kinase domain), and 3QRJ (ABL1 kinase domain). Assessment of the biochemical, hematological, and histopathological parameters in mice upheld the security and adequacy of the nanoconjugate compared to free drug. Although perspective investigations are warranted, in a condition like drug resistance in leukemia, this nanoconjugate would display a productive approach in cancer therapeutics.
authors.affiliation: 1 Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre (RCC), Thiruvananthapuram, India.
authors.forename: Alphy Rose
authors.initials: AR
authors.lastname: James
authors.affiliation: 1 Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre (RCC), Thiruvananthapuram, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Unnikrishnan
authors.affiliation: 2 Indian Institute of Information Technology and Management-Kerala (IIITM-K), Thiruvananthapuram, India.
authors.forename: R
authors.initials: R
authors.lastname: Priya
authors.affiliation: 1 Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre (RCC), Thiruvananthapuram, India.|3 Chemical Sciences & Technology Division (CSTD), CSIR - National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Thiruvananthapuram, India.
authors.forename: Manu M
authors.initials: MM
authors.lastname: Joseph
authors.affiliation: 2 Indian Institute of Information Technology and Management-Kerala (IIITM-K), Thiruvananthapuram, India.
authors.forename: T K
authors.initials: TK
authors.lastname: Manojkumar
authors.affiliation: 4 Clinical Laboratory Services, Regional Cancer Centre (RCC), Thiruvananthapuram, India.
authors.forename: K
authors.initials: K
authors.lastname: Raveendran Pillai
authors.affiliation: 1 Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre (RCC), Thiruvananthapuram, India.
authors.forename: R
authors.initials: R
authors.lastname: Shiji
authors.affiliation: 1 Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre (RCC), Thiruvananthapuram, India.
authors.forename: G U
authors.initials: GU
authors.lastname: Preethi
authors.affiliation: 5 Division of Pediatric Oncology, Regional Cancer Centre (RCC), Thiruvananthapuram, India.
authors.forename: P
authors.initials: P
authors.lastname: Kusumakumary
authors.affiliation: 1 Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre (RCC), Thiruvananthapuram, India.
authors.forename: T T
authors.initials: TT
authors.lastname: Sreelekha
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D026942:DNA Topoisomerases / Q000235:genetics; D003692:Delayed-Action Preparations / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics; D005936:Glucans / Q000627:therapeutic use*; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D058726:Nanoconjugates / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D005936:Glucans; D058726:Nanoconjugates; D011993:Recombinant Fusion Proteins; D000068877:Imatinib Mesylate; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D026942:DNA Topoisomerases
keywords: Cytotoxicity; P-glycoprotein; imatinib; multidrug resistance; polysaccharide