A Hybrid Membrane-Biomimetic Nanoplatform for Synergistic Photothermal/Photodynamic Therapy of Hypoxic Tumors

Abstract

Breast cancer continues to be the primary malignancy impacting women globally. Traditional therapies are frequently limited by non-specific distribution of drugs, systemic toxic effects, and resistance to multiple drugs. Biomimetic nanotechnology offers a promising solution to overcome these barriers by enhancing tumor accumulation and therapeutic efficiency. Herein, we develop a biomimetic nanoparticle delivery system with bovine serum albumin (BSA) serving as a carrier molecule to co-load the photosensitizer indocyanine green (ICG) and the oxygen-carrying material perfluorohexane (PFH). These nanoparticles are camouflaged with a hybrid membrane obtained from 4T1 tumor cells and erythrocytes. The results demonstrated that this hybrid coating conferred these nanoparticles with prolonged circulation and homologous targeting capabilities, dramatically boosting localization at the neoplastic location. Moreover, PFH can alleviate the hypoxic microenvironment of malignant tumors. Under 808 nm laser illumination, the nanoparticle-based synergistic photothermal and amplified photodynamic therapy effectively ablated tumors and demonstrated robust antitumor efficacy, lengthening the life expectancy of laboratory mice harboring established tumor xenografts. This study thus offers a hybrid membrane-based biomimetic nanoplatform for effective therapy of hypoxic tumors.