Losartan-IR820-Loaded Polydopamine Nanoparticles for CO2-Generating Ultrasound Imaging-Guided Photothermal/Photodynamic Therapies of Triple-Negative Breast Cancer

Abstract

Constructing efficient theranostic nanoparticles (NPs) to improve the therapeutic effect is a great challenge for triple-negative breast cancer (TNBC). Theranostic NPs fail to reach an ideal therapeutic effect due to high tumor solid stress and poor penetration in the extracellular matrix. The LST-IR820-CaNPs are rationally designed with desired therapeutic and ultrasound imaging properties, in which polydopamine (PDA) in conjunction with glutathione (GSH) is used as the template for CaCO3 mineralization in situ, equipped with the antihypertensive agent losartan (LST) and the photosensitizer new indocyanine green (IR820). The biocompatibility, drug release, photothermal and photodynamic effects, ultrasound imaging, and antitumor evaluation are investigated thoroughly. Under near-infrared (NIR) laser irradiation, LST-IR820-CaNPs produce singlet oxygen (1O2) and heat by converting absorbed laser energy. The LST-IR820-CaNPs possess effective antitumor activity, which is benefited from synergistic photothermal (PTT)/photodynamic (PDT) therapy and exploitation of LST to reduce solid stress of the tumor through depletion of collagen I. The NPs generate echogenic signals in an acidic form from carbon dioxide (CO2) bubbles generated from CaCO3, expressing stable ultrasound (US) imaging functions. The LST-IR820-CaNPs exhibit negligible systemic toxicity and excellent biocompatibility, thus being potential theranostic NPs for US imaging and therapy of TNBC.