Synergistic Effect of Cold Atmospheric Plasma and Drug Loaded Core-shell Nanoparticles on Inhibiting Breast Cancer Cell Growth

Abstract

Nano-based drug delivery devices allowing for effective and sustained targeted delivery of therapeutic agents to solid tumors have revolutionized cancer treatment. As an emerging biomedical technique, cold atmospheric plasma (CAP), an ionized non-thermal gas mixture composed of various reactive oxygen species, reactive nitrogen species, and UV photons, shows great potential for cancer treatment. Here we seek to develop a new dual cancer therapeutic method by integrating promising CAP and novel drug loaded core-shell nanoparticles and evaluate its underlying mechanism for targeted breast cancer treatment. For this purpose, core-shell nanoparticles were synthesized via co-axial electrospraying. Biocompatible poly (lactic-co-glycolic acid) was selected as the polymer shell to encapsulate anti-cancer therapeutics. Results demonstrated uniform size distribution and high drug encapsulation efficacy of the electrosprayed nanoparticles. Cell studies demonstrated the effectiveness of drug loaded nanoparticles and CAP for synergistic inhibition of breast cancer cell growth when compared to each treatment separately. Importantly, we found CAP induced down-regulation of metastasis related gene expression (VEGF, MTDH, MMP9, and MMP2) as well as facilitated drug loaded nanoparticle uptake which may aid in minimizing drug resistance-a major problem in chemotherapy. Thus, the integration of CAP and drug encapsulated nanoparticles provides a promising tool for the development of a new cancer treatment strategy.

Cold atmospheric plasma manipulation of proteins in food systems

“…Chen et al (2016) reported up to 162% increase in the activity of α-amylase in brown rice treated by low-pressure plasma at 3kV power input over 24 hours of germination (Chen et al, 2016). This result is in agreement with the findings of Lee et al (2016). Puač et al (2014) also found that the activity of superoxide dismutase (SOD) and catalase (CAT) enzymes increased following the exposure of carrot cells to atmospheric radio-frequency plasma.…”

“…However, there is still a lack of investigation on the possible benefits of ACP treatment for improving the 18 encapsulation efficiency. Zhu et al (2016) observed that thermal stability, electrical properties, and mechanical strength of drug-encapsulated nanoparticles are ameliorated by the impact of ACP. Hasirci et al (2010) suggest that plasma exposure can lead to the higher hydrophilicity of poly D, L-lactide-co-glycolide (PLGA) films and consequently enhanced cell adhesion.…”

“…A number of recent papers (Takai, et al, 2012;Surowsky et al, 2013 andTammineedi et al, 2013;Bußler et al, 2015;Mirsa et al, 2015;Zhang et al, 2015;Bahrami et al, 2016;Lee et al, 2016;Mirsa et al, 2016;Segat et al, 2016) have concentrated on the fundamental reactions between atmospheric-pressure plasma and proteins, particularly enzymes, in the model of food systems. They discuss the impacts of plasma on the activity and the structure of endogenous/exogenous enzymes, and on techno-functional properties of proteins.…”

Cold Atmospheric Plasma induces silver nanoparticle uptake, oxidative dissolution and enhanced cytotoxicity in Glioblastoma multiforme cells

“…Since then, studies using nanomaterials with various sizes and compositions have been used. For example, electrosprayed core-shell nanoparticle fabricated with 5-Fluorouracil synergistically inhibited cell growth of epithelial breast cancer cells MBA-MD-231 when used with CAP [31]. The plasma jet device using helium and oxygen gas in combination with Iron NPs significantly decreased viability of human breast adenocarcinoma cancer cells, MCF-7 [32].…”

Low dose Cold Atmospheric Plasma induces membrane oxidation, stimulates endocytosis and enhances uptake of nanomaterials in Glioblastoma multiforme cells

“…Meanwhile, AuNPs are known to be readily manufactured and designed for targeting delivery of various compounds into cells. Therefore, they have emerged as a promising reagent, combined with CAP, for anti-cancer therapy in recent studies 4,9,10 . In our previous study, we explored the potential of a combination treatment of CAP with gold nanoparticles, which showed promising synergistic cytotoxicity to U373MG Glioblastoma multiforme (GBM) cells 11 .…”