Smart Hybrid Nanocomposite for Photodynamic Inactivation of Cancer Cells with Selectivity.

Photodynamic therapy has been efficiently applied for cancer therapy. Here, we have fabricated the folic acid (FA)- and pheophorbide A (PA)-conjugated FA/PA@Fe3O4 nanoparticle (smart hybrid nanocomposite, SHN) to enhance the photodynamic inactivation (PDI) of specific cancer cells. SHN coated with the PDI agent is designed to have selectivity for the folate receptor (FR) expressed on cancer cells. Structural characteristics and morphology of the fabricated MNPs were studied with X-ray diffraction and scanning electron microscopy. The photophysical properties of SHN were investigated with absorption, emission spectroscopies, and Fourier transform infrared spectroscopy. In addition, the magnetic property of Fe3O4 nanoparticle (MNP) can be utilized for the collection of SHNs by an external magnetic field. The photofunctionality was given by the photosensitizer, PA, which generates reactive oxygen species by irradiation of visible light. Generation of singlet oxygen was directly evaluated with time-resolved phosphorescence spectroscopy. Biocompatibility and cellular interaction of SHN were also analyzed by using various cancer cells, such as KB, HeLa, and MCF-7 cells which express different levels of FR on the surface. Cellular adsorption and the PDI effect of SHN on the various cancer cells in vitro were correlated well with the surface expression levels of FR, suggesting potential applicability of SHN on specific targeting and PDI of FR-positive cancers.

Target-oriented photofunctional nanoparticles (TOPFNs) for selective photodynamic inactivation of Methicillin-resistant Staphylococcus aureus (MRSA).

To inactivate methicillin-resistant Staphylococcus aureus (MRSA) with minimum damage to host cells and tissue, target-oriented photofunctional nanoparticles (TOPFNs) were fabricated and characterized. MRSA is a predominant infective pathogen even in hospital and non-hospital environments due to its ability to develop high levels of resistance to several classes of antibiotics through various pathways. To solve this major problem, photodynamic inactivation (PDI) method applies to treat antibiotic-resistant bacteria. PDI involves the photosensitizer (PS) and light with a specific wavelength to be able to apply for a non-invasive therapeutic procedure to treat pathogenic bacteria by inducing apoptosis or necrosis of microorganisms. However, most current PDI researches have suffered from the instability of PDI agents in the biological environment due to the lack of selectivity and low solubility of PDI agents, which leads to the low PDI efficiency. In this study, the TOPFNs were fabricated by an esterification reaction to introduce hematoporphyrin (HP) and MRSA antibody to the surface of Fe3O4 nanoparticles. The TOPFNs were designed as dispersible PDI agent in biological condition, which was effectively used for selectively capturing and killing of MRSA. The capture efficiency TOPFNs was compared with PFNs as a negative control. The results showed that the capture efficiency of TOPFNs and PFNs was 95.55% and 6.43% in MRSA and L-929 cell mixed condition, respectively. And TOPFNs have a selective killing ability for MRSA with minimum damage to L-929 cells. Furthermore, PDI effect of TOPFNs was evaluated on the mice in vivo condition in order to check the possibility of practical medical application.

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.

Functional manipulation of dendritic cells by photoswitchable generation of intracellular reactive oxygen species.

Reactive oxygen species (ROS) play an important role in cellular signaling as second messengers. However, studying the role of ROS in physiological redox signaling has been hampered by technical difficulties in controlling their generation within cells. Here, we utilize two inert components, a photosensitizer and light, to finely manipulate the generation of intracellular ROS and examine their specific role in activating dendritic cells (DCs). Photoswitchable generation of intracellular ROS rapidly induced cytosolic mobilization of Ca(2+), differential activation of mitogen-activated protein kinases, and nuclear translocation of NF-κB. Moreover, a transient intracellular ROS surge could activate immature DCs to mature and potently enhance migration in vitro and in vivo. Finally, we observed that intracellular ROS-stimulated DCs enhanced antigen specific T-cell responses in vitro and in vivo, which led to delayed tumor growth and prolonged survival of tumor-bearing mice when immunized with a specific tumor antigen. Therefore, a transient intracellular ROS surge alone, if properly manipulated, can cause immature DCs to differentiate into a motile state and mature forms that are sufficient to initiate adaptive T cell responses in vivo.

Photosensitizer and vancomycin-conjugated novel multifunctional magnetic particles as photoinactivation agents for selective killing of pathogenic bacteria.

Novel multifunctional magnetic particles (MMPs) conjugated with photosensitizer and vancomycin were fabricated by surface modification of Fe(3)O(4) particles. The capacities to target, capture and inactivate pathogenic bacteria and good biocompatibility suggest that the MMPs have great potentials as photodynamic inactivation agents for serious bacterial contamination.