Cytotoxic enhancement of hexapeptide-conjugated micelles in EGFR high-expressed cancer cells

Abstract

Objectives: The aim of this study was to develop the hexapeptide-conjugated active targeting micelles for delivery of doxorubicin (DOX) and paclitaxel (PTX) to EGFR high-expressed cancer cells.

Methods: A hexapeptide, which mimicked the EGFR, was applied as a targeting ligand. The active targeting micelles were prepared using the synthesized poly(D,L-lactide-co-glycolide)–PEG copolymer conjugated with the hexapeptide. The micelles were used for encapsulating DOX and/or PTX, and the cellular uptake, in vitro drug release and cellular viability of drug-loaded peptide-conjugated and peptide-free micelles were investigated.

Results: The particle size of drug-loaded peptide-conjugated and peptide-free micelles was < 150 nm with narrow size distribution. The uptake of peptide-conjugated micelles was more efficient in EGFR high-expressed MDA-MB-468 and SKOV3 cells than in EGFR low-expressed HepG2 cells. The in vitro release of DOX and PTX was faster in pH 4.0 (500 U lipase) than in pH 7.4 release medium. The cytotoxicity in terms of IC₅₀ of DOX/PTX-loaded peptide-conjugated micelles was 4.8-folds lower than that of peptide-free micelles and 18.2-folds lower than DOX/PTX drug solution in SOKV3 cells.

Conclusion: The peptide-conjugated micelles acted as a nanocarrier to increase intracellular accumulation of anticancer drugs in EGFR high-expressed SKOV3 cancer cells to enhance cell cytotoxicity.

Keywords::

• doxorubicin
• EGFR
• hexapeptide
• micelles
• paclitaxel

Acknowledgment

The authors thank Chia Wen Liu for cellular co-localization study and Fu Hsiung Chang for Zetasizer usage.

Notes