title: "Clickable" Nanogels via Thermally Driven Self-Assembly of Polymers: Facile Access to Targeted Imaging Platforms using Thiol-Maleimide Conjugation.
abstract: Multifunctionalizable nanogels are fabricated using thermally driven self-assembly and cross-linking of reactive thermoresponsive copolymers. Nanogels thus fabricated can be easily conjugated with various appropriately functionalized small molecules and/or ligands to tailor them for various applications in delivery and imaging. In this study, a poly(ethylene glycol)-methacrylate-based maleimide-bearing copolymer was cross-linked with a dithiol-based cross-linker to synthesize nanogels. Because of lower critical solution temperature (LCST) around 55 °C in aqueous media, these copolymers assemble into nanosized aggregates when heated to this temperature, and they are cross-linked using the thiol-maleimide conjugation. Nanogels thus fabricated contain both thiol and maleimide groups in the same cross-linked nanogels. Postgelation functionalization of the residual maleimide and thiol groups is demonstrated through conjugation of a thiol-bearing hydrophobic dye (BODIPY-SH) and N-(fluoresceinyl) maleimide, respectively. In addition, to demonstrate the utility of multifunctionality of these nanogels, a thiol-bearing cyclic-peptide-based targeting group, cRGDfC, and N-(fluoresceinyl)-maleimide-based fluorescent tag was conjugated to nanogels in aqueous media. Upon treatment with breast cancer cell lines, MDA-MB-231, it was deduced from cellular internalization studies using fluorescence microscopy and flow cytometry that the peptide carrying constructs were preferentially internalized. Overall, a facile synthesis of multifunctionalizable nanogels that can be tailored using effective conjugation chemistry under mild conditions can serve as promising candidates for various applications.
authors.affiliation: Department of Chemistry, Bogazici University , 34342 Bebek, Istanbul, Turkey.
authors.forename: Bugra
authors.initials: B
authors.lastname: Aktan
authors.affiliation: Department of Chemistry, Bogazici University , 34342 Bebek, Istanbul, Turkey.
authors.forename: Laura
authors.initials: L
authors.lastname: Chambre
authors.affiliation: Department of Chemistry, Bogazici University , 34342 Bebek, Istanbul, Turkey.|Center for Life Sciences and Technologies, Bogazici University , 34342 Bebek, Istanbul, Turkey.
authors.forename: Rana
authors.identifier: 0000-0003-4803-5811
authors.initials: R
authors.lastname: Sanyal
authors.affiliation: Department of Chemistry, Bogazici University , 34342 Bebek, Istanbul, Turkey.|Center for Life Sciences and Technologies, Bogazici University , 34342 Bebek, Istanbul, Turkey.
authors.forename: Amitav
authors.identifier: 0000-0001-5122-8329
authors.initials: A
authors.lastname: Sanyal
mesh_terms: D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008301:Maleimides / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D058105:Polymerization; D011108:Polymers / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013696:Temperature; D014407:Tumor Cells, Cultured
chemical_list: D005456:Fluorescent Dyes; D008301:Maleimides; D000080385:Nanogels; D011108:Polymers; D013438:Sulfhydryl Compounds; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine