In-vitro investigation of cold atmospheric plasma induced photodynamic effect by Indocyanine green and Protoporphyrin IX.

BACKGROUND: Photodynamic therapy (PDT) is one of the non-invasive methods for the treatment of superficial malignant cancers. One of the limiting challenges of PDT is the hypoxic conditions during treatment that reduces PDT Efficiency. Because of ROS and free radicals in plasma flame output, Cold atmospheric plasma (CAP) may improve treatment efficiency. In this study, the effect of plasma-induced photodynamic effect of two Photosensitizers (PSs) include Indocyanine green (ICG) and Protoporphyrin IX (PPIX) on two cell lines (MCF-7 and HT-29) was investigated. METHODS: First, toxicity of different concentrations of PSs (5-50 µM) were examined on cell lines. After that, we surveyed low toxicity of PSs concentrations with different plasma radiation doses. To quantitative of cell survival, MTT assay was performed after 48 h. Finally, in order to statistical analysis of data, we used SPSS software (version 20) and also in order to better comparison the results, we used indexes such as Plasma sensitivity index and Synergism index. RESULTS: The results indicate that in most irradiant conditions; for ICG + CAP group, PSI > 1 and SI < 1 in the both of cell line (P < 0.05). Also for PPIX + CAP group in most irradiant conditions, only in the HT-29 cell line can it be said with certainty that both indexes (PSI and SI) are higher than 1 (P < 0-05). CONCLUSION: The results show that the plasma-induced photodynamic therapy with ICG and PPIX has more effective results on MCF-7 (breast cancer) and HT-29 (colon cancer) cell line, respectively. Also, the synergistic effect was observed only for PPIX in the HT-29 cell line.

Investigation of the emission spectra and cytotoxicity of TiO2 and Ti-MSN/PpIX nanoparticles to induce photodynamic effects using X-ray.

BACKGROUND: Photodynamic therapy (PDT) has been recognized as an effective method for cancer treatment; however, it suffers from limited tissue penetration depth. X-rays are ideal excitation sources for activating self-lighting nanoparticles that can penetrate through deep tumor tissues and convert the X-rays to visible light. In this study, Ti-MSN/PpIX nanoparticles for X-ray induced photodynamic therapy was synthesized. Preparation, characterization, and emission spectrum of Ti-MSN/PpIX nanoparticles as well as PDT activity and toxicity of the nanoparticles on HT-29 cell line were investigated. METHODS: Firstly, mesoporous silica nanoparticles (MSN) were synthesized through sol-gel method. Then, TiO2 and PpIX were loaded in MSN. Next, the emission spectra of TiO2, Ti-MSN, and Ti-MSN/PpIX nanoparticles, while activated by X-ray (6 MVp), were recorded. In addition, viability of cells after treatment by Ti-MSN/PpIX nanoparticles and X-ray irradiation was studied. RESULTS: SEM, TEM and FESEM images of the spherical composite nanoparticles showed that their dimensions were changed by incorporating Ti and organic compound of PpIX. Two-dimensional hexagonal structure with d100-spacing was about 3.5 nm with particle sizes of 70-110 nm. The optical characteristics of TiO2 nanoparticles showed strong emission lines, which effectively overlapped with the absorption wavelengths of protoporphyrin IX (PpIX). Cellular experiments showed Ti-MSN/PpIX nanoparticles have proper biocompatibility, however, after X-ray irradiation, significant decrease of cell viability in the presence of the nanoparticles was observed. CONCLUSION: The presented X-PDT method could enhance RT efficacy and is enable that allows for reducing X-ray dose exposure to healthy tissues to overcome radio-resistant tumors.

A comparative study on generating hydroxyl radicals by single and two-frequency ultrasound with gold nanoparticles and protoporphyrin IX.

Sonodynamic therapy (SDT) is a new manner of killing cancer cells based on the cytotoxic interactions of ultrasound with sonosensitizing agents. It is shown that gold nanoparticles (GNPs) increase the efficiency of cavitation activity of ultrasound. In this study the influence of a single and/or two frequencies of ultrasound waves to generate hydroxyl radicals (·OH) was assessed in the presence of protoporphyrin IX (PpIX) and/or GNPs. Ultrasound cavitation activity was determined by recording fluorescence signals from chemical terephthalic acid (TA) dosimeters with or without PpIX and/or GNPs at the frequencies of 0.8 and 2.4 MHz individually and aggregately. To study hydroxyl radicals, experiments were performed with and without hydroxyl radical scavengers mannitol, histidine, and sodium azide. Cavitation activity was amplified by increasing ultrasound intensity and exposure time. The cavitation activity induced by dual ultrasound frequency was remarkably higher than the summation of effects produced by individual frequencies. All three scavengers reduced the fluorescence signal level. The effect of GNPs on intensifying cavitation activity at higher frequency was greater than that of lower frequency. PpIX showed a more effective sonosensitizing property at the lower frequency. Also, estimated synergism at dual frequency irradiation was improved in the presence of GNPs. We found that GNPs increased hydroxyl radical production at 2.4 MHz and that PpIX increased hydroxyl radical production at 0.8 MHz. Dual frequency exposure was more effective than single frequency exposure. PpIX at low frequency and gold nanoparticles at high frequency both enhance sonodynamic treatment efficacy.