Efficient suppression of oral squamous cell carcinoma through spatial dimension conversion drug delivery systems-enabled immunomodulatory-photodynamic therapy

Patients with oral squamous cell carcinoma (OSCC) encounter challenges in achieving efficient antitumor immunity, primarily due to the inherent pathophysiological characteristics of solid tumors affecting drug accumulation and penetration. Insufficient T-cells and immune escape induced by tumor-associated macrophages (TAMs) further exacerbate these issues. This study utilized M1 macrophage membrane-modified spatial dimension conversion drug delivery systems (SDDDSs) and introduced photosensitizers chlorophyll Pyro and the immune agonist R848. This innovative approach enhanced tumor targeting and accumulation by transforming stimulus-responsive size-reductive SDDDSs into smaller-sized iRGD-Pyro and R848 within the extracellular tumor microenvironment (TME). This facilitated effective drug penetration into deep tumor regions and cellular uptake. The synergistic treatment strategy for OSCC, combining photodynamic therapy (PDT) and tumor immunotherapy, induced tumor cell apoptosis, triggered immunogenic cell death (ICD), polarized TAMs towards the M1 phenotype, promoted sufficient T-cell infiltration, and resulted in significant therapeutic outcomes. This approach offers a promising avenue for future OSCC therapeutic interventions.