Red blood cell membrane-camouflaged nanoparticles loaded with AIEgen and Poly(I:C) for enhanced tumoral photodynamic-immunotherapy

Red blood cell (RBC)-mimicking nanoparticles (NPs) offer a promising platform for drug delivery because of their prolonged circulation time, reduced immunogenicity and specific targeting ability. Herein, we report the design and preparation of RBC membrane-bound NPs (M@AP), for tumoral photodynamic-immunotherapy. The M@AP is formed by self-assembly of the positively charged aggregation-induced emission luminogen (AIEgen) (named P2-PPh3) and the negatively charged polyinosinic:polycytidylic acid (Poly(I:C)), followed by RBC membrane encapsulation. P2-PPh3 is an AIE-active conjugated polyelectrolyte with additional photosensitizing ability for photodynamic therapy (PDT), while Poly(I:C) serves as an immune-stimulant to stimulate both tumor and immune cells to activate immunity, and thus reduces tumor cell viability. When applied in tumor-bearing mice, the M@AP NPs are enriched in both the tumor region as a result of an enhanced permeability and retention (EPR) effect, and the spleen because of the homing effect of the RBC-mimicking shell. Upon light irradiation, P2-PPh3 promotes strong ROS generation in tumor cells, inducing the release of tumor antigens (TA). The anti-tumor immunity is further enhanced by the presence of Poly(I:C) in M@AP. Thus, this strategy combines the PDT properties of the AIE-active polyelectrolyte and immunotherapy properties of Poly(I:C) to achieve synergistic activation of the immune system for anti-tumor activity, providing a novel strategy for tumor treatment. Immunotherapy has great potential, but the response of some tumors to immunotherapy is not high. Herein, we developed a biomimetic red cell membrane loaded with aggregation-induced emission luminogen and polyinosinic:polycytidylic acid nanoparticles to enhance the efficacy of tumor immunotherapy.

Automated summary

The study presents a novel strategy for tumor photodynamic-immunotherapy using red blood cell-mimicking nanoparticles, combining photodynamic therapy and immunotherapy properties to achieve synergistic immune system activation for anti-tumor activity. The nanoparticles demonstrated significant anti-tumor efficacy in a tumor-bearing mouse model, showing promising potential in enhancing tumor immunotherapy.