Vitamin B12-conjugated sericin micelles for targeting CD320-overexpressed gastric cancer and reversing drug resistance

Abstract

Aim: Our previous research has introduced sericin micelles to reverse drug resistance. However, these micelles could not selectively bind to gastric cancer (GC) cells. We developed vitamin B12 (VB12) conjugated sericin micelles for targeted GC therapy.

Materials & methods: We used VB12, sericin, synthetic poly(γ-benzyl-L-glutamate) (PBLG) and paclitaxel (PTX) to develop VB12-conjugated and PTX-loaded micelles (VB12-sericin-PBLG-PTX). Then we explored their physicochemical properties, cellular uptake and antitumor mechanism.

Results: VB12-sericin-PBLG-PTX micelles were proved to be of appropriate particle size, have good dispersion and are bio-safe. Following transcobalamin II (CD320)-receptor-mediated endocytosis, these swallowed micelles with GC-targeting and enhanced cellular uptake abilities, alter mitochondrial transmembrane potential/apoptosis pathway and reverse drug resistance.

Conclusion: VB12-sericin-PBLG-PTX micelles are promising materials for GC-targeted clinical applications.

Keywords: drug resistance; gastric cancer; micelle; sericin; vitamin B12.