期刊
REACTIVE & FUNCTIONAL POLYMERS
卷 71, 期 3, 页码 315-323出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.reactfunctpolym.2010.10.011
关键词
Block copolymer; Nanogel; Atom transfer radical polymerization; Targeting; TAG-72; mAb CC49
资金
- USA National Institute of Health (NIH) [CA116590]
- Department of Defense USA MRMC [06108004]
- NIH [RR021937]
Novel surface-functionalized cross-linked nanogels were developed as a platform to allow conjugation of monoclonal antibodies (mAb) for targeted drug delivery. Well-defined diblock copolymers of poly(ethylene glycol)-b-poly(methacrylic acid) (PEG-b-PMA) with PEG terminal aldehyde functionality were synthesized by atom transfer radical polymerization (ATRP) and characterized by GPC and H-1 NMR. These copolymers were used to prepare nanogels via condensation of PEG-b-PMA with Ca2+ ions into micelle-like aggregates, cross-linking of the PMA/Ca2+ cores and removal of Ca2+ ions. The resulting nanogels represent highly swollen spherical polyelectrolyte particles with free terminal aldehyde functionalities at the nonionic PEG chains. A reductive amination reaction between aldehyde groups and amino groups of mAb resulted in effective conjugation to the nanogels of mAb CC49 against tumor-associated glycoprotein 72 (TAG-72). The mAb retained the binding affinity to bovine submaxillary mucin after conjugation as shown by surface plasmon resonance (SPR). Therefore, aldehyde-functionalized nanogels can be linked to mAb using a simple, one-step approach. They may have potential for targeted delivery of diagnostic and therapeutic agents to tumors. (C) 2010 Elsevier Ltd. All rights reserved.
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