Nanoparticles derived from insect exoskeleton modulates NLRP3 inflammasome complex activation in cervical cancer cell line model

Abstract Background: Immune evasion is an important hallmark of cancer progression and tumourigenesis. Among the cancer types, cervical cancer has very high global prevalence, severely affecting female reproductive health. Its preponderance is also observed in the Indian health sector. Results: The NLRP3 inflammasome, an intracellular complex regulates the innate immune activity and a variant gene of it has been significantly associated with cervical cancer development. We aimed to evaluate the potential role of our chitosan engineered nanoparticles (CSNP) and gallic acid conjugated chitosan (gCSNP), to modulate the NLRP3 inflammasome complex in cervical cancer cell lines to explore their novel physicochemical properties. The encapsulation of gallic acid (GA) with chitosan was performed using ion gelation method. The CSNP and gCSNP nanoparticles ranged between 155 - 181 nm as determined by zeta sizer. The conjugations were validated by FTIR and XRD analysis. In the cervical cell line model, CSNP suppressed NLRP3 inflammasome activation in contrast to gCSNP at higher doses. Conclusion: In contrast to gCSNP, the CSNP not only demonstrated inhibitory effect on the expression of genes coding for the NLRP3 inflammasome complex (signal 1 – priming) but also decreased relative expression of gene involved in the activation of NLRP3 inflammasome complex (signal 2 – activation). Conjugation of gallic acid reversed the immunosuppressor mimicking action of CSNP in cervical cancer cell line. Future research can reveal the immunomodulatory mechanism of CSNP may have its translational significance as potential treatment strategies targeting immune evasion as an important hallmark of cancer.