Well-Defined Single Polymer Nanoparticles for the Antibody-Targeted Delivery of Chemotherapeutic Agents

Abstract

Aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization was employed to prepare a series of linear copolymers of N,N-dimethylacrylamide (DMA) and 2-hydroxyethylacrylamide (HEAm) with narrow values over a molecular weight range spanning three orders of magnitude (103 to 106 Da). Trithiocarbonate-based RAFT chain transfer agents (CTAs) were grafted onto these scaffolds using carbodiimide chemistry catalyzed with DMAP. The resultant graft chain transfer agent (gCTA) was subsequently employed to synthesize polymeric brushes with a number of important vinyl monomer classes including acrylamido, methacrylamido, and methacrylate. Brush polymerization kinetics were evaluated for the aqueous RAFT polymerization of DMA from a 10 arm gCTA. Polymeric brushes containing hydroxyl functionality were further functionalized in order to prepare 2nd generation gCTAs which were subsequently employed to prepare polymers with a brushed-brush architecture with molecular weights in excess of 106 Da. The resultant single particle nanoparticles (SNPs) were employed as drug delivery vehicles for the anthracycline-based drug doxorubicin via copolymerization of DMA with a protected carbazate monomer (bocSMA). Cell-specific targeting functionality was also introduced via copolymerization with a biotin-functional monomer (bioHEMA). Drug release of the hydrazone linked doxorubicin was evaluated as function of pH and serum and chemotherapeutic activity was evaluated in SKOV3 ovarian cancer cells.

Department(s)

Materials Science and Engineering

Keywords and Phrases

Acrylic monomers; Chains; Copolymerization; Copolymers; Drug delivery; Free radical polymerization; Grafting (chemical); Living polymerization; Molecular weight; Monomers; Nanoparticles; Polymerization, Chemotherapeutic activity; Chemotherapeutic agents; Drug delivery vehicles; Hydroxyl functionality; N ,n-dimethylacrylamide; Polymerization kinetics; Reversible addition-fragmentation chain transfer polymerization; Three orders of magnitude, Polymers

International Standard Serial Number (ISSN)

1759-9954

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2015 Royal Society of Chemistry, All rights reserved.

Publication Date

01 Feb 2015

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