title: Click conjugation of peptide to hydrogel nanoparticles for tumor-targeted drug delivery.
abstract: Here we introduce a modified peptide-decorated polymeric nanoparticle (NP) for cancer cell targeting, which can deliver drugs, such as doxorubicin (Dox), to several kinds of cancer cells. Specifically, we employ a nucleolin-targeting NP, with a matrix based on a copolymer of acrylamide (AAm) and 2-carboxyethyl acrylate (CEA). The negatively charged co(CEA-AAm) NP was conjugated with a nucleolin-targeting F3 peptide using a highly efficient and specific copper(I) catalyzed azide-alkyne click reaction. F3 peptide binds to angiogenic tumor vasculatures and other nucleolin overexpressing tumor cells. Attaching F3 peptide onto the NP increases the NP uptake by the nucleolin-expressing glioma cell line 9L and the breast cancer cell line MCF-7. Notably, the F3-conjugated NPs show much higher uptake by the nucleolin-overexpressing glioma cell line 9L than that by the breast cancer cell line MCF-7, the latter having a lower expression of nucleolin on its plasma membrane surface. Moreover, the F3 peptide also dramatically enhances the uptake of co(CEA-AAm) NPs by the drug-resistant cell line NCI/ADR-RES. Also, with this F3-conjugated co(CEA-AAm) NP, a high loading and slow release of doxorubicin were achieved.
authors.affiliation: Department of Chemistry and ‡Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Qin
authors.forename: Hong
authors.initials: H
authors.lastname: Zong
authors.forename: Raoul
authors.initials: R
authors.lastname: Kopelman
mesh_terms: D020106:Acrylamide / Q000494:pharmacology; D000179:Acrylates / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage*; D010455:Peptides / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D011108:Polymers / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D000097796:Nucleolin
chemical_list: D020106:Acrylamide; D000179:Acrylates; D004317:Doxorubicin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D010455:Peptides; D010750:Phosphoproteins; D011108:Polymers; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C056360:3-acryloyloxypropionic acid