Nanoplatform Self-assembly From Small Molecules of Porphyrin Derivatives for NIR-II Fluorescence Imaging Guided Photothermal-immunotherapy

Abstract Combinatorial photothermal and immunotherapy have demonstrated great potential to remove primary tumors, suppress metastases, and prevent tumor recurrence. However, this strategy still confronts with many limitations, such as complex components, sophisticated construction and inadequate therapeutic efficacy. In this work, we develop small molecules of porphyrin derivatives (PPor) which can self-assemble into monodispersed nanoparticles without supplement of any other ingredients or surfactants. The formed PPor nanoparticles (PPor NPs) exhibit highly photothermal conversion efficiency of 70% and NIR-II luminous abilities originated from the strong intramolecular charge transfer (ICT) effect of D-A structure under 808 nm laser irradiation, thus achieving NIR-II fluorescence imaging guided photothermal therapy (PTT) against primary tumor with a high cure rate. More importantly, tumor-associated antigens (TAAs) together with damage-associated molecular patterns (DAMPs) released from PTT-treated cancer cells are proved to elicit immune responses in some degree. After combination with programmed cell death-1 (PD-1) antibody, a robust systematic antitumor immunity are generated to restrain both primary and abscopal tumors growth, prolong survival, prevent pulmonary metastasis on an aggressive 4T1 murine breast tumor model. Thus, this study provides a promising therapeutic paradigm with porphyrin derivatives nano-assembly as phototheranostic agents for the treatment of aggressive tumor with high efficiency.