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Jiang, Yanyan
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article
Polymer-albumin conjugate for the facilitated delivery of macromolecular platinum drugs
Abstract
<p>The delivery of macromolecular platinum drugs into cancerous cells is enhanced by conjugating the polymer to albumin. The monomers <i>N</i>-(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(HPMA<sub>14</sub>-co-(Ac-DAP-Boc)<sub>9</sub>) and a molecular weight of <i>M</i><sub>n</sub> = 7600 g mol<sup>-1</sup> (<i>Ð</i> = 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.</p>