A structure-property relationship study of the well-defined telodendrimers to improve hemocompatibility of nanocarriers for anticancer drug delivery

Changying Shi, Dekai Yuan, Shikha Nangia, Gaofei Xu, Kit Lam, Juntao Luo

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

A series of telodendrimer (a linear polyethyelene glycol-block-dendritic oligo-cholic acid) have been synthesized via a bottom-up approach to optimize the hemocompatibility of the nanocarrier. Numbers of hydrophilic glycerol groups were introduced onto the polar surface of cholic acid to reduce the plasma membrane lytic activity of telodendrimers. An interesting result was observed: only an optimum number of glycerol introduced could reduce the hemolytic properties of the nanocarrier; on the contrary, more glycerols or the amino-glycerol substitution onto cholic acid significantly increased the hemolytic properties of the nanocarriers. To further elucidate the structure-property relationship, the molecular dynamic approach was used to simulate the conformation of the subunits of telodendrimers with different glycerol substitution, and the binding energies and the polar surface areas of the hairpin conformations were calculated to explain the membrane activities of nanocarriers. In addition, these telodendrimer subunits were synthesized and their membrane activities were tested directly, which validated the computational prediction and correlated with the observed hemolytic activity of nanocarriers. The glycerol substitution sustained the facial amphiphilicity of cholic acid, maintaining the superior drug loading capacity (paclitaxel and doxorubicin), stability, cell uptake, and anticancer efficacy of payloads. The in vivo optical imaging study indicated that the optimized nanocarriers can specifically deliver drug molecules to the tumor sites more efficiently than free drug administration, which is essential for the enhanced cancer treatment.

Original languageEnglish (US)
Pages (from-to)6878-6888
Number of pages11
JournalLangmuir
Volume30
Issue number23
DOIs
StatePublished - Jun 17 2014

ASJC Scopus subject areas

  • Electrochemistry
  • Condensed Matter Physics
  • Surfaces and Interfaces
  • Materials Science(all)
  • Spectroscopy

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