Dental Pulp Stem Cell‐Derived Intracellular Vesicles Inhibit OSCC by Delivering PTEN to Suppress PI3K / AKT / mTOR Signalling Pathway

Oral squamous cell carcinoma (OSCC) represents a globally predominant type of oral malignancy with escalating incidence, featuring aggressive biological behaviour, prominent metastatic potential and poor clinical outcomes. Emerging evidence positions dental pulp stem cell-sourced intracellular vesicles (DPSC-IVs) as novel therapeutic vectors in regenerative oncology, citing their low immunogenicity, favourable safety profile and ability to modulate tumour microenvironment. In this study, DPSC-IVs significantly inhibited OSCC progression both in vitro and in vivo, suppressing tumour cell proliferation, invasion and colony formation while simultaneously promoting apoptosis. Notably, the antitumor effect of DPSC-IVs was further enhanced by combining them with autophagy inhibitor 3-methyladenine (3-MA), which synergistically suppressed the PI3K/AKT/mTOR pathway and enhanced mitochondrial stress while suppressing residual cytoprotective autophagy. Mechanistically, DPSC-IVs served as carriers of PTEN into OSCC cells, which in turn suppressed oncogenic PI3K/AKT signalling and induced excessive mitophagy. Taken together, this study indicated that DPSC-IVs could suppress OSCC through dual mechanisms, highlighting their potential as a promising and clinically translatable therapeutic option with advantages in safety and scalable production.