title: Polymer-albumin conjugate for the facilitated delivery of macromolecular platinum drugs.
abstract: The delivery of macromolecular platinum drugs into cancerous cells is enhanced by conjugating the polymer to albumin. The monomers N-(2-hydroxypropyl)methacrylamide (HPMA) and Boc protected 1,3-diaminopropan-2-yl acrylate (Ac-DAP-Boc) are copolymerized in the presence of a furan protected maleimide functionalized reversible addition-fragmentation chain transfer (RAFT) agent. The resulting polymer with a composition of P(HPMA14 -co-(Ac-DAP-Boc)9 ) and a molecular weight of Mn = 7600 g mol(-1) (Đ = 1.24) is used as a macromolecular ligand for the conjugation to the platinum drug. Thermogravimetric analysis reveals full conjugation. After deprotection of the maleimide functionality of the polymer, the reactive polymer is conjugated to albumin using the Cys34 functionality. The conjugation is monitored using size exclusion chromatography, MALDI-TOF (matrix assisted laser desorption ionization time-of-flight), and SDS Page (sodium dodecyl sulphate polyacrylamide gel electrophoresis). The polymer-albumin conjugates self-assemble in water into nanoparticles of sizes of around 80 nm thanks to the hydrophobic nature of the platinum drugs. The albumin coated nanoparticles are readily taken up by ovarian cancer cell lines and they show superior toxicity compared to a control sample without protein coating.
authors: Centre for Advanced Macromolecular Design, School of Chemistry and School of Chemical Engineering, University of New South Wales, Sydney, 2052, Australia.|Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bezmialem Vakif University, 34093, Fatih, Istanbul, Turkey.
authors: Aydan
authors: A
authors: Dag
authors: Centre for Advanced Macromolecular Design, School of Chemistry and School of Chemical Engineering, University of New South Wales, Sydney, 2052, Australia.
authors: Yanyan
authors: Y
authors: Jiang
authors: Centre for Advanced Macromolecular Design, School of Chemistry and School of Chemical Engineering, University of New South Wales, Sydney, 2052, Australia.|Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia (UTM), 81310, UTM Skudai, Johor, Malaysia.
authors: Khairil Juhanni Abd
authors: KJ
authors: Karim
authors: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, 2052, Australia.
authors: Gene
authors: G
authors: Hart-Smith
authors: Centre for Advanced Macromolecular Design, School of Chemistry and School of Chemical Engineering, University of New South Wales, Sydney, 2052, Australia.
authors: Wei
authors: W
authors: Scarano
authors: Centre for Advanced Macromolecular Design, School of Chemistry and School of Chemical Engineering, University of New South Wales, Sydney, 2052, Australia.
authors: Martina H
authors: MH
authors: Stenzel
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000179:Acrylates / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers; D004339:Drug Compounding; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D020128:Inhibitory Concentration 50; D008301:Maleimides / Q000737:chemistry; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000737:chemistry*
chemical_list: D000178:Acrylamides; D000179:Acrylates; D000970:Antineoplastic Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008301:Maleimides; D012710:Serum Albumin, Bovine; D016650:Fluorescein-5-isothiocyanate; D002945:Cisplatin; C032976:N-(2-hydroxypropyl)methacrylamide
keywords: Albumin; micelles; nanoparticles; platinum drugs; polymer-protein conjugates