A drug-specific nanocarrier design for efficient anticancer therapy

Changying Shi, Dandan Guo, Kai Xiao, Xu Wang, Lili Wang, Juntao Luo

Research output: Contribution to journalArticle

75 Citations (Scopus)

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.

Original languageEnglish (US)
Article number7449
JournalNature Communications
Volume6
DOIs
StatePublished - Jul 9 2015
Externally publishedYes

Fingerprint

therapy
drugs
Pharmaceutical Preparations
Drug delivery
Doxorubicin
Molecules
delivery
Therapeutics
affinity
Small Molecule Libraries
Chemical properties
molecules
Feasibility Studies
Toxicity
Tumors
Nanoparticles
Copolymers
versatility
toxicity
peptides

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

A drug-specific nanocarrier design for efficient anticancer therapy. / Shi, Changying; Guo, Dandan; Xiao, Kai; Wang, Xu; Wang, Lili; Luo, Juntao.

In: Nature Communications, Vol. 6, 7449, 09.07.2015.

Research output: Contribution to journalArticle

Shi, Changying ; Guo, Dandan ; Xiao, Kai ; Wang, Xu ; Wang, Lili ; Luo, Juntao. / A drug-specific nanocarrier design for efficient anticancer therapy. In: Nature Communications. 2015 ; Vol. 6.
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