Tumor microenvironment remodeling in oral cancer: Application of plant derived-natural products and nanomaterials.

Oral cancers consist of squamous cell carcinoma (SCC) and other malignancies in the mouth with varying degrees of invasion and differentiation. For many years, different modalities such as surgery, radiation therapy, and classical chemotherapy drugs have been used to control the growth of oral tumors. Nowadays, studies have confirmed the remarkable effects of the tumor microenvironment (TME) on the development, invasion, and therapeutic resistance of tumors like oral cancers. Therefore, several studies have been conducted to modulate the TME in various types of tumors in favor of cancer suppression. Natural products are intriguing agents for targeting cancers and TME. Flavonoids, non-flavonoid herbal-derived molecules, and other natural products have shown promising effects on cancers and TME. These agents, such as curcumin, resveratrol, melatonin, quercetin and naringinin have demonstrated potency in suppressing oral cancers. In this paper, we will review and discuss about the potential efficacy of natural adjuvants on oral cancer cells. Furthermore, we will review the possible therapeutic effects of these agents on the TME and oral cancer cells. Moreover, the potential of nanoparticles-loaded natural products for targeting oral cancers and TME will be reviewed. The potentials, gaps, and future perspectives for targeting TME by nanoparticles-loaded natural products will also be discussed.