An adjuvant codelivery nanosystem using Poria cocos polysaccharide for strengthened antitumor immunophototherapy

As novel anticancer treatment, phototherapy has recently shown promising immunotherapy effect. However, photodynamic (PDT) or photothermal (PTT) alone is not sufficient to achieve satisfactory anticancer immunities. Certain polysaccharides can stimulate immune responses, but its application as an adjuvant in anticancer phototherapy has not been clearly studied. In this study, we established PLGA nanoparticles (PPS-ICG@PLGA NPs), loading polysaccharides from Poria cocos (PPS) as adjuvant, and using ICG as phototherapeutic molecule to study its anticancer immunities. The PPS was proved to enhance the ICD and immunomodulatory activity of the nanoparticle. Following intravenous injection, the PPS-ICG@PLGA NPs can accumulate in tumor site up to 24 h. Under NIR laser irradiation, the PTT/PDT associated with PPS induced cascade anticancer effects to activate cytotoxic T lymphocytes (CTLs). In vivo antitumor studies confirmed that the administration of PPS-ICG@PLGA NPs increased the ratio of CD4⁺ and CD8⁺ T cells in both tumor and spleen, enhanced DCs maturation in tumor and reversed the intratumor infiltration of regulatory T cells (Tregs) in tumor. These results demonstrate the application potential of PPS in promoting the immunotherapy efficacy of phototherapy, and also propose PPS-ICG@PLGA as a promising nanosystem for photoimmunotherapy.