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Development of Functional Poly(amido amine) CXCR4 Antagonists with the Ability to Mobilize Leukocytes and Deliver Nucleic Acids
Author(s) -
Wang Yan,
Hazeldine Stuart T.,
Li Jing,
Oupický David
Publication year - 2015
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201400608
Subject(s) - chemokine receptor , nucleic acid , cationic polymerization , cxcr4 , chemokine , chemistry , cxcr4 antagonist , cancer cell , transfection , cancer research , receptor , monomer , pharmacology , biochemistry , cancer , combinatorial chemistry , medicine , polymer , organic chemistry , gene
CXCR4 chemokine receptor plays a crucial role in metastatic spread of multiple types of cancer. The present study reports on synthesis of functional polymers based on newly synthesized CXCR4‐inhibiting monomers. The resultant linear polymeric CXCR4 antagonists (PCX) show improved ability to inhibit CXCR4 when compared with the monomers. The CXCR4 antagonism provides PCX with the ability to mobilize leukocytes from bone marrow to peripheral blood and to inhibit cancer cell invasion. Due to their cationic nature, PCX can form polyplexes with DNA and mediate efficient transfection. The reported findings validate PCX as promising dual‐function polymeric drugs that can deliver therapeutic nucleic acids and improve cancer therapy by simultaneously inhibiting CXCR4 chemokine receptor.