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Nat Commun. 2015 Jul 9;6:7449. doi: 10.1038/ncomms8449.

A drug-specific nanocarrier design for efficient anticancer therapy.

Author information

1
Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York 13210, USA.
2
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, Chengdu 610041, China.

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.

PMID:
26158623
PMCID:
PMC4499863
DOI:
10.1038/ncomms8449
[Indexed for MEDLINE]
Free PMC Article

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