title: Design of smart HPMA copolymer-based nanomedicines.
abstract: 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.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA; Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: jindrich.kopecek@utah.edu.
authors.forename: Jindřich
authors.initials: J
authors.lastname: Kopeček
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015195:Drug Design; D006801:Humans; D008689:Methacrylates / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D050997:Nanomedicine / Q000379:methods* / Q000639:trends; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008689:Methacrylates; D011108:Polymers; C032802:hydroxypropyl methacrylate
keywords: Coiled-coil peptides; Degradable polymeric carriers; Drug-free macromolecular therapeutics; HPMA; Oligonucleotides; Self-assembly