title: Multifunctional particles for melanoma-targeted drug delivery.
abstract: New magnetic-based core-shell particles (MBCSPs) were developed to target skin cancer cells while delivering chemotherapeutic drugs in a controlled fashion. MBCSPs consist of a thermo-responsive shell of poly(N-isopropylacrylamide-acrylamide-allylamine) and a core of poly(lactic-co-glycolic acid) (PLGA) embedded with magnetite nanoparticles. To target melanoma cancer cells, MBCSPs were conjugated with Gly-Arg-Gly-Asp-Ser (GRGDS) peptides that specifically bind to the α(5)β(3) receptors of melanoma cells. MBCSPs consist of unique multifunctional and controlled drug delivery characteristics. Specially, they can provide dual drug release mechanisms (a sustained release of drugs through degradation of PLGA core and a controlled release in response to changes in temperature via thermo-responsive polymer shell), and dual targeting mechanisms (magnetic localization and receptor-mediated targeting). Results from in vitro studies indicate that GRGDS-conjugated MBCSPs have an average diameter of 296 nm and exhibit no cytotoxicity towards human dermal fibroblasts up to 500 μg ml(-1). Further, a sustained release of curcumin from the core and a temperature-dependent release of doxorubicin from the shell of MBCSPs were observed. The particles also produced a dark contrast signal in magnetic resonance imaging. Finally, the particles were accumulated at the tumor site in a B16F10 melanoma orthotopic mouse model, especially in the presence of a magnet. Results indicate great potential of MBCSPs as a platform technology to target, treat and monitor melanoma for targeted drug delivery to reduce side effects of chemotherapeutic reagents.
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, 500 UTA Blvd, Arlington, TX 76019, USA.
authors.forename: Aniket S
authors.initials: AS
authors.lastname: Wadajkar
authors.forename: Zarna
authors.initials: Z
authors.lastname: Bhavsar
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Ko
authors.forename: Bhanuprasanth
authors.initials: B
authors.lastname: Koppolu
authors.forename: Weina
authors.initials: W
authors.lastname: Cui
authors.forename: Liping
authors.initials: L
authors.lastname: Tang
authors.forename: Kytai T
authors.initials: KT
authors.lastname: Nguyen
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D057446:Hydrodynamics; D019344:Lactic Acid / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D019047:Phantoms, Imaging; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013499:Surface Properties / Q000187:drug effects
chemical_list: D000180:Acrylic Resins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C052970:poly-N-isopropylacrylamide; D011100:Polyglycolic Acid; D019344:Lactic Acid