Mucoadhesive Nucleoside-Based Hydrogel Delays Oral Leukoplakia Canceration

Area of Science:

• Biomaterials Science
• Oral Medicine
• Cancer Research

Background:

• Oral squamous cell carcinomas (OSCCs) often develop from oral potentially malignant disorders (OPMDs), with oral leukoplakia (OLK) being the most common.
• Current treatments for OLK face challenges due to limited efficacy and poor adhesion of traditional chemotherapeutic drugs.
• There is a need for novel agents combining mucoadhesion with anti-OLK effects to prevent malignant transformation.

Purpose of the Study:

• To fabricate and evaluate a novel isoguanosine-tannic acid (isoG-TA) supramolecular hydrogel for treating OLK.
• To investigate the anti-OLK efficacy and underlying mechanisms of isoG-TA and guanosine-tannic acid (G-TA) hydrogels.
• To assess the potential of these hydrogels in preventing the progression of OLK to OSCC.

Main Methods:

• Fabrication of isoG-TA supramolecular hydrogel using dynamic borate esters.
• In vitro assessment of cell viability using dysplastic oral keratinocytes (DOKs).
• In vivo evaluation of hydrogels in an OLK model to assess canceration prevention.
• Investigation of isoG and TA mechanisms, including adenosine kinase (ADK) and mammalian target of rapamycin (mTOR) pathway interactions, and reactive oxygen species (ROS) reduction.

Main Results:

• Both isoG-TA and G-TA hydrogels demonstrated ideal mucoadhesive properties and integrated anti-OLK activities.
• In vitro studies showed that isoG and TA inhibited DOK proliferation.
• In vivo studies indicated that both hydrogels have potential in preventing OLK canceration, with G-TA showing a statistically better effect.
• IsoG was found to inhibit DOK proliferation by affecting the mTOR pathway via ADK binding.
• TA reduced ROS in DOKs, potentially inhibiting proliferation by inducing G0/G1 cell cycle arrest.

Conclusions:

• An innovative isoG-TA hydrogel with excellent adhesion and anti-OLK properties was successfully developed.
• Both isoG and TA exhibit in vitro inhibition of DOKs, suggesting therapeutic potential.
• IsoG-TA and G-TA hydrogels show promise in delaying OLK malignant transformation, offering a potential strategy for OLK management and OSCC prevention.