Abstract
BackgroundImmune 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.ResultsThe 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 and 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.ConclusionIn 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.Graphical abstract
Highlights
Immune evasion is an important hallmark of cancer progression and tumourigenesis
The FTIR of CS was compared with Gallic acid conjugated chitosan nanoparticle (gCSNP)
The gCSNP displayed a decrease in the peak at 1320 and 1380 cm−1 attributed to the NH bending observed in the glucosamine units and at 1420 cm−1 when compared with chitosan engineered nanoparticles (CSNP)
Summary
Immune evasion is an important hallmark of cancer progression and tumourigenesis. Cervical cancer has very high global prevalence, severely affecting female reproductive health. Cervical malignancy is the fourth most prevalent neoplasm globally and second most common among Indian women (Arbyn et al 2020; Mishra et al 2016). Inflammation induced through microbial or danger signals affects all stages of tumor development. The pro-inflammatory cytokines, IL-1β and IL-6, are important mediators for inflammation-induced tumourigenesis (Moossavi et al 2018). The NLRP3 inflammasome is a multimeric protein complex that regulates the innate immune activity through modulation of the production of pro-inflammatory cytokines. The role of NLRP3 inflammasome activation in tumourigenesis, transformation and invasion, remains a conundrum (Moossavi et al 2018). There is a lack of adequate therapeutic strategies targeting key immune signaling pathways involving the inflammasome complex in cancer treatment
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