Eradication of Plasmodium falciparum from Erythrocytes by Controlled Reactive Oxygen Species via Photodynamic Inactivation Coupled with Photofunctional Nanoparticles

We investigated the antimalarial effect of photodynamic inactivation (PDI) coupled with magnetic nanoparticles (MNPs) as a potential strategy to combat the emergence of drug-resistant malaria and resurgence of malaria after treatment. Because the malarial parasite proliferates within erythrocytes, PDI agents need to be taken up by erythrocytes to eradicate the parasite. We used photofunctional MNPs as the PDI agent because nanosized particles were selectively taken up by Plasmodium-infected erythrocytes and remained within the intracellular space due to the enhanced permeability and retention effect. Also, the magnetism of Fe₃O₄ nanoparticles can easily be utilized for the collection of photofunctional nanoparticles (PFNs), and the uptaken PFNs infected the erythrocytes after photodynamic treatment with external magnetics. Photofunctionality was provided by a photosensitizer, namely, pheophorbide A, which generates reactive oxygen species (ROS) under irradiation. PAs were covalently bonded to the surface of the MNPs. The morphology and structural characteristics of the MNPs were investigated by scanning electron microscopy and X-ray diffraction (XRD), whereas the photophysical properties of the PFNs were studied with Fourier transform infrared, absorption, and emission spectroscopies. Generation of singlet oxygen, a major ROS, was directly confirmed with time-resolved phosphorescence spectroscopy. To evaluate the ability of PFNs to kill malarial parasites, the PDI effect of PFNs was evaluated within the infected erythrocytes. Furthermore, malarial parasites were completely eradicated from the erythrocytes after PDI treatment using PFNs on the basis of an 8 day erythrocyte culture test.