title: Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy.
abstract: Combination therapy of multiple drugs through a single system is exhibiting high therapeutic effects. We investigate nanocarrier mediated inhibitory effects of topotecan (TPT) and quercetin (QT) on triple negative breast cancer (TNBC) (MDA-MB-231) and multi drug resistant (MDR) type breast cancer cells (MCF-7) with respect to cellular uptake efficiency and therapeutic mechanisms as in vitro and in vivo. The synthesized mesoporous silica nanoparticle (MSN) pores used for loading TPT; the outer of the nanoparticles was decorated with poly (acrylic acid) (PAA)-Chitosan (CS) as anionic inner-cationic outer layer respectively and conjugated with QT. Subsequently, grafting of arginine-glycine-aspartic acid (cRGD) peptide on the surface of nanocarrier (CPMSN) thwarted the uptake by normal cells, but facilitated their uptake in cancer cells through integrin receptor mediated endocytosis and the dissociation of nanocarriers due to the ability to degrade of CS and PAA in acidic pH, which enhance the intracellular release of drugs. Subsequently, the released drugs induce remarkable molecular activation as well as structural changes in tumor cell endoplasmic reticulum, nucleus and mitochondria that can trigger cell death. The valuable CPMSNs may open up new avenues in developing targeted therapeutic strategies to treat cancer through serving as an effective drug delivery podium.
authors.affiliation: Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, Periyar University, Salem-636011, TamilNadu, INDIA.
authors.forename: Chandran
authors.initials: C
authors.lastname: Murugan
authors.affiliation: Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, Periyar University, Salem-636011, TamilNadu, INDIA.
authors.forename: Kathirvel
authors.initials: K
authors.lastname: Rayappan
authors.affiliation: King Institute of Preventive Medicine &Research, Guindy, Chennai 600 032, Tamil Nadu, INDIA.
authors.forename: Ramar
authors.initials: R
authors.lastname: Thangam
authors.affiliation: Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, Periyar University, Salem-636011, TamilNadu, INDIA.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Bhanumathi
authors.affiliation: Department of Zoology, Bharathiar University, Coimbatore, 641 046, Tamil Nadu, INDIA.
authors.forename: Krishnamurthy
authors.initials: K
authors.lastname: Shanthi
authors.affiliation: Department of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200 240, CHINA.
authors.forename: Raju
authors.initials: R
authors.lastname: Vivek
authors.affiliation: Department of Animal Science, Bharathidasan University, Tiruchirappalli, 620 024, Tamil Nadu, INDIA.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Thirumurugan
authors.affiliation: Nanotechnology Section, Department of Biomedical Engineering, Rajiv Gandhi Institute of Technology and Research Centre, Hebbal, Bangalore, 560 032, Karnataka, INDIA.
authors.forename: Atanu
authors.initials: A
authors.lastname: Bhattacharyya
authors.affiliation: King Institute of Preventive Medicine &Research, Guindy, Chennai 600 032, Tamil Nadu, INDIA.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Sivasubramanian
authors.affiliation: King Institute of Preventive Medicine &Research, Guindy, Chennai 600 032, Tamil Nadu, INDIA.
authors.forename: Palani
authors.initials: P
authors.lastname: Gunasekaran
authors.affiliation: Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, Periyar University, Salem-636011, TamilNadu, INDIA.
authors.forename: Soundarapandian
authors.initials: S
authors.lastname: Kannan
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology; D012822:Silicon Dioxide / Q000737:chemistry / Q000494:pharmacology; D019772:Topotecan / Q000737:chemistry / Q000494:pharmacology; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D009842:Oligopeptides; C006903:carbopol 940; D012822:Silicon Dioxide; C047981:arginyl-glycyl-aspartic acid; D019772:Topotecan; D048271:Chitosan; D011794:Quercetin