89P - Cold atmospheric plasma-activated fluids as a potential new intravesical agent for the treatment of bladder cancer

Background

Cold atmospheric plasma (CAP) has been studied for cancer treatment. One of its forms, CAP activated liquids (CAPAL), may be an alternative to intravesical agents to treat bladder cancer (BC). The surgical bipolar resectoscope, when in use, is a source of thermal plasma (TP), which exerts effects on the surrounding sodium chloride solution for irrigation (NaCl 0.9%), transforming it into a TP activated liquid (TPAL), which is produced in very close contact with the bladder wall. To accelerate a possible introduction of plasma-activated liquid in the treatment of BC, we decided to compare the properties and biological effects of CAPAL and TPAL.

Methods

An electronic device was designed by our group to create CAP. TP was produced by a resectoscope. NaCl 0.9% was exposed to CAP or TP during short periods of time (30, 60, 120, 180 seconds) creating CAPAL or TPAL. The reactive oxygen and nitrogen species (RONS) activity was evaluated using the OxiSelect™ RONS Assay Kit in each activated liquid. BC cell lines, TCCSUP (grade IV) and HT-1376 (grade III), were incubated with CAPAL or TPAL. Metabolic activity was evaluated by MTT assay and protein content by SRB assay, 24h post-incubation.

Results

In comparison to non irradiated NaCl 0.9%, both CAPAL and TPAL, in all exposure times resulted in a significant rise in the activity of RONS. Regarding the biological activity of the activated liquids in the BC cell lines, both CAPAL and TPAL induced a decrease in cell metabolic activity and protein content in an exposure-time dependent manner. CAPAL induced a higher antitumor effect on the high-grade cell line (TCCSUP), while TPAL had a similar effect on both cell lines. Comparing the two activated liquids, CAPAL required longer exposure times to achieve the same effects observed with TPAL at lower exposure times.

Conclusions

This study shows that PAL can be a therapeutic agent for BC. Both TPAL and CAPAL showed similar biologics in BC cells. Currently, in clinical practice, TPAL is already in close contact with the bladder wall during surgery, however only briefly and diluted by irrigation. This work intends to get one step closer to demonstrate that CAPAL can be a safe and effective BC treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Foundation For Science And Technology (FCT), Portugal, through the Strategic Projects, UIDB/04539/2020, UIDP/04539/2020, and by COMPETE-FEDER, reference number POCI-01-0145-FEDER-007440. Scholarship grants from FCT and European Social Funding to E.P. (2021.05543. BD).

Disclosure

All authors have declared no conflicts of interest.