Near-Infrared Light-Boosted Photodynamic-Immunotherapy based on sulfonated Metal-Organic framework nanospindle

Photoactive metal–organic frameworks have achieved great success in the photodynamic therapy (PDT). However, poor therapeutic effect under near-infrared (NIR) irradiation becomes a big changllege for the fully eradication of tumors by using photodynamic MOFs. Herein, a spindle-shaped PCN-222-SO3H (PCN-SU) with the enhanced NIR absorption was synthesized by the sulfonating reaction. After sulfonation, the strong intramolecular hydrogen bonds between the introduced sulfonic anions and TCPP ligands could induce the distortion of porphyrin rings. This distortion leads to the lower energy gap of HOMO and LOMO, thereby increasing the absorption in the near-infrared region. Comparing with PCN-222, great improvements of photoactive performances in PCN-SU result in the boosting generation of singlet oxygen under NIR irradiation. Furthermore, PCN-SU gives high efficiency to trigger the immunogenic cell death (ICD) and also to stimulate the maturation of dendritic cells than that of prototype PCN-222. The combination of immune checkpoint inhibitors (anti-PD-1) with the photodynamic PCN-SU largely enhances the infiltration of cytotoxic T cells in the tumor site under NIR irradiation, and thus to obtain the tumor suppression of 99.6 % in vivo. This new sulfonating strategy provides a new idea for enhancing the photoactivity of the porphyrin-based delivery system, which is beneficial to the improvement of PDT and related combined treatments.