A pH-Sensitive Smart Monomer Prevents Oral Cancer Progression

Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide, and the development of anti-OSCC materials is urgent. The tumor microenvironment has been identified as a significant characteristic of cancer, with the pHe value in OSCC ranging from 6.56 to 6.97. Given the acidic nature of OSCC, the creation of pH-sensitive antitumor materials has become a prominent area of research. A pH-sensitive tertiary amine monomer, dodecylmethylaminoethyl methacrylate (DMAEM), has been previously synthesized. This study aims to evaluate the impact of DMAEM on OSCC. The results demonstrated that DMAEM inhibited the proliferation, migration, and invasion of OSCC cells. Furthermore, it promoted apoptosis and autophagy of OSCC cells, with its anti-OSCC effect being strengthened in the acidic environment. In a subcutaneous transplantation tumor model, DMAEM inhibited the growth of OSCC and expression of Ki-67. The analysis of 16S rDNA sequencing data revealed that DMAEM had no significant impact on the Alpha/Beta diversity of the gastrointestinal tract microbiota in mice and had minimal effect on its composition. Overall, this study suggests that DMAEM exhibits pH-responsive behavior in the acidic tumor microenvironment, effectively inhibiting OSCC without disturbing the gastrointestinal microbiota. These findings highlight the potential of DMAEM for clinical applications in OSCC treatment. A pH-sensitive tertiary amine monomer dodecylmethylaminoethyl methacrylate (DMAEM) inhibited proliferation, migration, and invasion of oral squamous cell carcinoma (OSCC) cells, and promoted apoptosis and autophagy of OSCC cells. The anti-OSCC effect was strengthened in acidic environment. DMAEM displayed a pH responsive effect and inhibited OSCC. Local use of DMAEM didn't disturb the gastrointestinal microbiota. DMAEM showed a potential for clinical application in OSCC treatment.image (c) 2024 WILEY-VCH GmbH