Design of smart HPMA copolymer-based nanomedicines

JOURNAL OF CONTROLLED RELEASE

卷:240

Article

Yang, Jiyuan¹  Kopecek, Jindrich^1,2 

[1] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA

[2] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA

关键词: Degradable polymeric carriers;    Drug-free macromolecular therapeutics;    HPMA;    Oligonucleotides;    Coiled-coil peptides;    Self-assembly;   

DOI  :  10.1016/j.jconrel.2015.10.003

来源: Elsevier

【 摘 要 】

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. (C) 2015 Elsevier B.V. All rights reserved.

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