Delivery of coumarin-containing all-trans retinoic acid derivatives via targeted nanoparticles encapsulating indocyanine green for chemo/photothermal/photodynamic therapy of breast cancer

Abstract

Development of chemo/photothermal/photodynamic therapy with nanoplatforms offers a promising strategy for effective cancer treatment. Recently, all-trans retinoic acid (ATRA), as a potential antitumor drug, has attracted great attention due to its antitumor activity. In this study, a novel coumarin-containing ATRA (AC) and indocyanine green (ICG) dye-loaded nanoparticles with the targeted ligand cyclic (Arg-Gly-Asp-D-Phe-Lys) (cRGD) peptide were fabricated by self-assembly and used as a new theranostic nanoplatform for chemo/photothermal/photodynamic therapy. The as-formed nanoparticles (AC/ICG-TNPs) had a diameter of around 133 nm with uniform monodispersity. Additionally, AC/ICG-TNPs showed marked stability under normal physiological conditions. However, it could rapidly release drugs in a mild acidic microenvironment. Moreover, confocal microscopic observations confirmed that the uptake of AC/ICG-TNPs increased in the breast cancer cells, particularly in MDA-MB-231 cells, probably mediated by cRGD via specific recognition of the overexpressed integrin α_vβ₃. Moreover, free AC exhibited stronger cytotoxic effects than free ATRA in the MTT assay, and AC/ICG-TNPs were demonstrated to possess excellent antitumor efficacy when exposed to NIR irradiation through the combination therapy. Hence, the therapeutic method designed in this study is a good candidate for improved bioactivity of ATRA and site-specific combinational therapy against breast cancer.