Modulation of Intracellular Oxygen Pressure by Dual-Drug Nanoparticles to Enhance Photodynamic Therapy

Oxygen plays an essential role in the photodynamic therapy (PDT) of cancer. However, hypoxia inside tumors severely attenuates the therapeutic effect of PDT. To address this issue, a novel strategy is reported for cutting off the oxygen consumption pathway by using sub-50 nm dual-drug nanoparticles (NPs) to attenuate the hypoxia-induced resistance to PDT and to enhance PDT efficiency. Specifically, dual-drug NPs that encapsulate photosensitizer (PS) verteporfin (VER) and oxygen-regulator atovaquone (ATO) with sub-50 nm diameters can penetrate deep into the interior regions of tumors and effectively deliver dual-drug into tumor tissues. Then, ATO released from NPs efficiently reduce in advance cellular oxygen consumption by inhibition of mitochondria respiratory chain and further heighten VER to generate greater amounts of O-1(2) in hypoxic tumor. As a result, accompanied with the upregulated oxygen content in tumor cells and laser irradiation, the dual-drug NPs exhibit powerful and overall antitumor PDT effects both in vitro and in vivo, and even tumor elimination. This study presents a potential appealing clinical strategy in photodynamic eradication of tumors.