Immune-enhanced and tumor-targeted PDT cascade therapy for oral squamous cell carcinoma utilizing a carrier-free BRD4 inhibitor/PDT agent nanocomplex

Photodynamic therapy (PDT) has been a promising therapeutic approach for oral squamous cell carcinoma (OSCC) on account of its ability to provoke immunogenic cell death (ICD) properties. However, unaggressive and intolerable immune responses hinder its tumor immunotherapy efficacy. Notably, the Bromodomain-containing protein 4 (BRD4) inhibitor JQ1, which could trigger ICD and eliminate the expression of Programmed death-ligand 1(PD-L1) in tumor cells, has been noted for its potential in tumor immunotherapy. To fully combine their benefits meanwhile reduce shortcomings, for the first time, we co-formulated the PDT photosensitizers Chlorin e6 (Ce6) and BRD4 inhibitor JQ1 into a carrier-free nanocomplexes- RGD peptide (NPsR), and investigated their mechanism of action against OSCC. The study revealed that NPsR could simultaneously achieve ideal tissue penetration and proactively accumulate on tumor tissues under the assistance of RGD peptide. This nanocomplex initiated an amplifying cascade reaction for tumor treatment, thereby restoring anti-tumor immune responses and enhancing therapeutic efficacy. Therefore, this carrier-free nanocomplex offers a promising solution for immune-enhanced PDT cascade therapy for OSCC.