Localized Fe(II)-Induced Cytotoxic Reactive Oxygen Species Generating Nanosystem for Enhanced Anticancer Therapy

The anticancer therapy on the basis of reactive oxygen species (ROS)-mediated cellular apoptosis has achieved great progress. However, this kind of theraputic strategy still faces some challenges such as light, photosensitizer and oxygen (O₂) dependence. In this article, a ROS-mediated anticancer therapy independent of light, photosensitizer and oxygen was established based on a Fe²⁺-induced ROS-generating nanosystem. First, artemisinin (ART) was loaded in porous magnetic supraparticles (MSP) by a nanodeposition method. Then, the poly(aspartic acid)-based polymer, which consisted of dopamine, indocyanine green, and polyethylene glycol side chain, was coated onto the surface of ART-loaded MSP. When the nanoparticles entered into cancer cells, a reaction of Fe²⁺-mediated cleavage of the endoperoxide bridge contained in ART occurred and subsequent a large amount of ROS was generated. Moreover, a NIR light was used to effectively increase the local temperature of tumor in virtue of the superior photothermal effects of MSP, which enabled us to accelerate the ROS generation and achieved an enhanced ROS yield. The newly developed nanodrug system displayed a high level of intracellular ROS generation, leading to the desired killing efficacy against malignant cells and solid tumor. This smart nanosystem holds great potential to overcome the existing barrier in PDT and opens a promising avenue for anticancer therapy.