[Paper Review] Micro-sized cold atmospheric plasma source for brain and breast cancer treatment

Zhitong Chen, Li Lin+5 more|arXiv (Cornell University)|Apr 18, 2018

Plasma Applications and Diagnostics40 references3 citations

TL;DR

This study develops a micro-sized cold atmospheric plasma (uCAP) source for targeted cancer therapy, demonstrating enhanced efficacy in killing glioblastoma and breast cancer cells using a 20 mm nozzle length. The uCAP generates reactive oxygen and nitrogen species that induce dose-dependent tumor cell death, with the 20 mm device showing superior effects due to synergistic reactive species delivery.

ABSTRACT

Micro-sized cold atmospheric plasma (uCAP) has been developed to expand the applications of CAP in cancer therapy. In this paper, uCAP devices with different nozzle lengths were applied to investigate effects on both brain (glioblastoma U87) and breast (MDA-MB-231) cancer cells. Various diagnostic techniques were employed to evaluate the parameters of uCAP devices with different lengths such as potential distribution, electron density, and optical emission spectroscopy. The generation of short- and long-lived species (such as hydroxyl radical (.OH), superoxide (O2-), hydrogen peroxide (H2O2), nitrite (NO2-), et al) were studied. These data revealed that uCAP treatment with a 20 mm length tube has a stronger effect than that of the 60 mm tube due to the synergetic effects of reactive species and free radicals. Reactive species generated by uCAP enhanced tumor cell death in a dose-dependent fashion and was not specific with regards to tumor cell type.

Motivation & Objective

• To develop a miniaturized cold atmospheric plasma (uCAP) source for precise cancer therapy.
• To evaluate the impact of varying nozzle lengths on plasma parameters and cancer cell viability.
• To investigate the role of reactive oxygen and nitrogen species (RONS) in uCAP-induced tumor cell death.
• To compare the efficacy of uCAP on glioblastoma (U87) and breast cancer (MDA-MB-231) cell lines.
• To optimize uCAP design for enhanced therapeutic outcomes in cancer treatment.

Proposed method

• Design and fabrication of uCAP devices with different nozzle lengths (20 mm and 60 mm).
• Use of electrical diagnostics to measure potential distribution and electron density in the plasma plume.
• Employment of optical emission spectroscopy to identify and quantify reactive species such as .OH, O2-, H2O2, and NO2-.
• Exposure of U87 glioblastoma and MDA-MB-231 breast cancer cells to uCAP for in vitro cytotoxicity assessment.
• Quantitative analysis of reactive species concentrations and their correlation with cell death rates.
• Dose-dependent treatment experiments to evaluate the relationship between plasma exposure and cancer cell viability.

Experimental results

Research questions

• RQ1 How does nozzle length in a micro-sized cold atmospheric plasma (uCAP) source influence the generation of reactive species and their delivery to cancer cells?
• RQ2 What is the relative cytotoxic effect of uCAP on glioblastoma (U87) and breast cancer (MDA-MB-231) cell lines?
• RQ3 Which reactive species (e.g., .OH, H2O2, O2-, NO2-) are most significantly produced by uCAP and contribute to tumor cell death?
• RQ4 Is the anti-cancer effect of uCAP dependent on the dose of plasma exposure, and how does this vary with device geometry?
• RQ5 What is the role of synergistic interactions between short- and long-lived reactive species in uCAP-induced cell death?

Key findings

• The 20 mm uCAP nozzle produced a stronger anti-cancer effect on both U87 glioblastoma and MDA-MB-231 breast cancer cells compared to the 60 mm nozzle.
• Reactive species such as hydroxyl radicals (.OH), superoxide (O2-), hydrogen peroxide (H2O2), and nitrite (NO2-) were detected and quantified in the plasma plume.
• The generation of short- and long-lived reactive species was enhanced in the 20 mm uCAP, contributing to its superior efficacy.
• Tumor cell death increased in a dose-dependent manner with increasing uCAP exposure time.
• The anti-cancer effect was not specific to tumor cell type, indicating broad applicability across cancer lines.
• The synergetic action of multiple reactive species was identified as a key factor in the enhanced cytotoxicity of the 20 mm uCAP device.