Design of smart HPMA copolymer-based nanomedicines

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)methacrylamid...

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Published inJournal of controlled release Vol. 240; pp. 9 - 23
Main Authors Yang, Jiyuan, Kopeček, Jindřich
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 28.10.2016
Subjects
Animals
Apoptosis - drug effects
Apoptosis - physiology
Coiled-coil peptides
Degradable polymeric carriers
Drug Design
Drug-free macromolecular therapeutics
HPMA
Humans
Methacrylates - administration & dosage
Methacrylates - chemistry
Methacrylates - metabolism
Nanomedicine - methods
Nanomedicine - trends
Neoplasms - drug therapy
Neoplasms - metabolism
Oligonucleotides
Polymers - administration & dosage
Polymers - chemistry
Polymers - metabolism
Self-assembly
Self-assembly
Degradable polymeric carriers
Coiled-coil peptides
HPMA
Drug-free macromolecular therapeutics
Oligonucleotides
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Summary: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. [Display omitted]
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-3
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ObjectType-Review-2
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2015.10.003