"Clickable" polymer-caged nanobins as a modular drug delivery platform.
Modularly clickable polymer-caged nanobins (PCNs) were prepared from liposome templates using a drop-in cholesterol-modified poly(acrylic acid) reagent followed by cross-linking with alkyne-functionalized diamine linker that allows for the conjugation of azide-modified targeting ligands via click ligation. These PCNs possess pH-responsive characteristics that can be used to trigger the release of encapsulated doxorubicin (DXR) payload inside the liposomal core under mild acidic conditions. After click-conjugation with azide-modified folate as an active targeting ligand, the resulting folate-conjugated, DXR-loaded PCNs (f-PCN(DXR)) demonstrated enhanced potency to folate receptor (FR)-positive tumor cells such as KB and OvCa432 over FR-negative MCF7 cells. f-PCN(DXR) can readily discriminate FR-positive tumor cells as a function of the level of cellular FR-expression, showing different degrees of potentiation in each cell. With both targeting functionalities and pH-sensitive drug-releasing triggers, f-PCN(DXR) was fifty-times more potent than the untargeted agent toward cancer cells that overexpress the folate target receptors.
Lee
Sang-Min
SM
Department of Chemistry, and the Center of Cancer Nanotechnology Excellence, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, USA.
Chen
Haimei
H
O'Halloran
Thomas V
TV
Nguyen
SonBinh T
ST
D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D001386:Azides / Q000737:chemistry; D002277:Carcinoma / Q000188:drug therapy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D003432:Cross-Linking Reagents; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy; D049329:Nanostructures / Q000737:chemistry*; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism
D000180:Acrylic Resins; D000903:Antibiotics, Antineoplastic; D001386:Azides; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes; D011956:Receptors, Cell Surface; D011092:Polyethylene Glycols; C006903:carbopol 940; D004317:Doxorubicin; D005492:Folic Acid; D002784:Cholesterol