A drug-specific nanocarrier design for efficient anticancer therapy

Changying Shi, Dandan Guo, Kai Xiao, Xu Wang, Lili Wang and Juntao Luo ()
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Changying Shi: State University of New York Upstate Medical University
Dandan Guo: State University of New York Upstate Medical University
Kai Xiao: Laboratory of Non-human Primate Disease Model Research, National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University
Xu Wang: State University of New York Upstate Medical University
Lili Wang: State University of New York Upstate Medical University
Juntao Luo: State University of New York Upstate Medical University

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: Abstract The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here we customize telodendrimers (linear dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug-binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumour targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery.

Date: 2015
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DOI: 10.1038/ncomms8449

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