Atom transfer radical polymerization in inverse miniemulsion: A versatileroute toward preparation and functionalization of microgelsanogels fortargeted drug delivery applications

摘要

This short review describes application of atom transfer radical polymerization (ATRP) in inverse min-iemulsion and disulfide-thiol exchange to prepare well-defined biodegradable functional nanogels(ATRP-nanogels). Due to the formation of uniform network, the ATRP-nanogels have higher swellingratios, better colloidal stability, and controlled degradation, as compared to nanogels prepared byconventional free-radical polymerization. Various water-soluble biomolecules such as anticancer drugs,carbohydrates, proteins, and star branched polymers were incorporated into ATRP-nanogels at highloading level, by in-situ physical loading or by in-situ chemical incorporation via covalent bonds. Thenanogels crosslinked with disulfide or polyester linkages were degraded either in the presence ofbiocompatible reducing agents or by hydrolysis for controllable release of the encapsulated drugs. ATRP-nanogels contain bromine end groups that enable further chain extension and functionalization withbiorelated molecules. They are also easily functionalized by copolymerization with functional monomersor use of functional ATRP initiator during synthesis. These functional nanogels have capability to befurther chemically modified and bioconjugated with cell-targeting proteins, antibodies, and integrin-binding peptides to increase cellular uptake via clathrin-mediated endocytosis. These results suggest thatsuch well-defined functional nanogels have great potential for targeted drug delivery applications.