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Research Article Open access CC BY 3.0

Block Copolymer Crosslinked Nanoassemblies Co-Entrapping Acridine Yellow and Doxorubicin for Cancer Theranostics

Pengxiao Cao, Andrei Ponta, JiAe Kim, Younsoo Bae

Journal of Pharmaceutical Research International · pp. 523–535 · Published 15 May 2013

10.9734/BJPR/2013/4574

Abstract

Aims: To develop block copolymer crosslinked nanoassemblies (CNAs) that co-entrap an imaging dye (Acridine Yellow: AY) and therapeutic agent (doxorubicin: DOX) as novel nanoparticle drug carriers for a combined application of drug delivery-based therapy and diagnostic imaging technologies (theranostics). Study Design: Physicochemical properties of AY-CNAs, such as molecular weight, particle size, surface charge, drug entrapment yield, and drug release profiles, were characterized prior to determining intracellular uptake profile, in vitro cytotoxicity, and in vivo tissue distribution patterns of the particles. Place and Duration of Study: Department of Pharmaceutical Sciences (University of Kentucky), between June 2012 and January 2013. Methodology: The AY-crosslinked CNAs (CNAs) were synthesized from biocompatible poly(ethylene glycol)-poly(aspartate) block copolymers by using AY as a crosslinker while DOX was physically entrapped in the particle through an ionic interaction. AY-CNAs and AY-CNAs with DOX were characterized to determine their particle properties (molecular weight, size, and optical properties), intracellular uptake and cytotoxicity in an in vitro cell culture system using human colon HT29 and lung A549 cancer cell lines, and tissue accumulation and tumor-preferential drug delivery efficiency ex vivo with a xenograft mouse tumor model. Results: AY-CNAs maintained nanoscale particle sizes (< 20 nm), fluorescence optical properties, and negative surface charge before and after drug entrapment. AY-CNAs with DOX were confirmed to kill cancer cells as effectively as free drug formulations, and to enhance intracellular uptake in vitro and tumor accumulation ex vivo. Conclusion: These results demonstrate that block copolymer nanoassemblies crosslinked with an imaging dye are promising platforms for the development of theranostic nanoparticle drug carriers.

Nanoparticles nanoassemblies drug carriers drug delivery imaging theranostics

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