Cancer cell membrane-coated sulindac-ortho ester nanoprodrug for inhibiting COX-2 expression and chemo-photothermal synergistic antitumor therapy

Abstract

The paper reported a cancer cell membrane bio-mimetic nanodrug to inhibit the expression of COX-2 in tumor area and realize enhanced chemo-photothermal synergistic anti-tumor effect. Ortho ester bond-coupled sulindac dimer (SU-OE) was first synthesized and co-assembled with doxorubicin to obtain pH-sensitive nanodrug (SU-OE@DOX NPs). Indocyanine green (ICG)-encapsulated H22 cell membrane vesicles (HM) were then co-extruded with SU-OE@DOX NPs to give the bio-mimetic nanoparticles (HM@I/NPs). HM@I/NPs displayed excellent stability and photothermal conversion efficiency. Compared to naked nanoparticles, the cell membrane-coated nanoparticles improved H22 cell uptake through homotypic targeting and effectively reduced internalization of macrophages. In vivo imaging results demonstrated that the nanoparticles could be enriched at tumor site and could raise the temperature of the tumor area to 56.7 °C under NIR laser irradiation. The released SU from HM@I/NPs can inhibit the expression of COX-2, and finally enhanced the chemo-PTT synergistic anti-tumor effect.