Design of smart HPMA copolymer-based nanomedicines

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• 作者：Jiyuan Yang^a ; Jindřich Kopeček^a ; ^b ; ^{jindrich.kopecek@utah.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Degradable polymeric carriers ; Drug-free macromolecular therapeutics ; HPMA ; Oligonucleotides ; Coiled-coil peptides ; Self-assembly
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 October 2016
• 年：2016
• 卷：240
• 期：Complete
• 页码：9-23
• 全文大小：1841 K

文摘

The state-of-the art in water-soluble macromolecular therapeutics has been reviewed. First the design principles for polymer-drug conjugates are discussed followed by two recent developments in the field: a) The design, synthesis and properties of backbone degradable N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates. The enhanced intravascular half-life of such conjugates creates a concentration gradient (blood vs. tumor) for an extended time interval resulting in increased solid tumor accumulation by enhanced permeability and retention (EPR) effect with concomitant increase in efficacy. b) Drug-free macromolecular therapeutics is a new paradigm in macromolecular therapeutics. Apoptosis in malignant cell is induced by crosslinking of cell surface non-internalizing receptors. Crosslinking of receptors is mediated by the biorecognition of two nanoconjugates containing high-fidelity complementary motifs (peptides or oligonucleotides). Results for the treatment of B cell lymphomas in animal models and patient cells demonstrate the high translational potential of this approach.