title: HER2 Targeted Breast Cancer Therapy with Switchable "Off/On" Multifunctional "Smart" Magnetic Polymer Core-Shell Nanocomposites.
abstract: Multifunctional magnetic polymer nanocombinations are gaining importance in cancer nanotheranostics due to their safety and their potential in delivering targeted functions. Herein, we report a novel multifunctional core-shell magnetic polymer therapeutic nanocomposites (NCs) exhibiting pH dependent "Off-On" release of drug against breast cancer cells. The NCs are intact in blood circulation ("Off" state), i.e., at physiological pH, whereas activated ("On" state) at intracellular acidic pH environment of the targeted breast cancer cells. The NCs are prepared by coating the cannonball (iron nanocore) with hydrophobic nanopockets of pH-responsive poly(d,l-lactic-co-glycolic acid) (PLGA) polymer nanoshell that allows efficient loading of therapeutics. Further, the nanocore-polymer shell is stabilized by poly(vinylpyrrolidone) (PVP) and functionalized with a targeting HER2 ligand. The prepared Her-Fe3O4@PLGA-PVP nanocomposites facilitate packing of anticancer drug (Tamoxifen) without premature release in the bloodstream, recognizing the target cells through binding of Herceptin antibody to HER2, a cell surface receptor expressed by breast cancer cells to promote HER2 receptor mediated endocytosis and finally releasing the drug at the intracellular site of tumor cells ("On" state) to induce apoptosis. The therapeutic efficiency of hemo/cytocompatible NCs drug delivery system (DDS) in terms of targeted delivery and sustained release of therapeutic agent against breast cancer cells was substantiated by in vitro and in vivo studies. The multifunctional properties of Her-Tam-Fe3O4@PLGA-PVP NCs may open up new avenues in cancer therapy through overcoming the limitations of conventional cancer therapy.
authors.affiliation: Proteomics & Molecular Cell Physiology Laboratory, Department of Zoology, Bharathiar University , Coimbatore 641 046, Tamil Nadu, India.
authors.forename: Raju
authors.initials: R
authors.lastname: Vivek
authors.affiliation: Proteomics & Molecular Cell Physiology Laboratory, Department of Zoology, Bharathiar University , Coimbatore 641 046, Tamil Nadu, India.|King Institute of Preventive Medicine & Research , Guindy, Chennai 600 032, Tamil Nadu, India.
authors.forename: Ramar
authors.initials: R
authors.lastname: Thangam
authors.affiliation: Department of Nanoscience and Technology, Bharathiar University , Coimbatore 641 046, Tamil Nadu, India.
authors.forename: Selvaraj Rajesh
authors.initials: SR
authors.lastname: Kumar
authors.affiliation: Proteomics & Molecular Cell Physiology Laboratory, Department of Zoology, Bharathiar University , Coimbatore 641 046, Tamil Nadu, India.
authors.forename: Chandrababu
authors.initials: C
authors.lastname: Rejeeth
authors.forename: Gopal Senthil
authors.initials: GS
authors.lastname: Kumar
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: Loyola Institute of Frontier Energy (LIFE), Loyola College , Chennai 600 034 Tamil Nadu, India.
authors.forename: Savariar
authors.initials: S
authors.lastname: Vincent
authors.forename: Dhanaraj
authors.initials: D
authors.lastname: Gopi
authors.forename: Soundarapandian
authors.initials: S
authors.lastname: Kannan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D060328:Magnetic Phenomena; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D058990:Molecular Targeted Therapy; D053761:Nanocomposites / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen
keywords: HER2 receptor; breast cancer; iron oxide; magnetic PLGA; pH-responsiveness; poly(d,l-lactic-co-glycolic acid); targeted cancer therapy