Nano-combined immunotherapy strategies have great advantages in primary tumor and metastases treatment. Targeted nanomaterials can regulate and strengthen the key steps in the cascade reaction of immune system, such as antigen release and presentation, immune cell-mediated killing, etc., so as to enhance the tumor immune cycle and best activate the immune system. At the same time, nano materials regulate tumor microenvironment, which can overcome tumor immune escape and increase therapeutic effects. However, great challenges still exist, such as biosafety of nanomaterials, tumor targeting, long-term stimulation of tumor immunogenicity and immune escape based on nanomaterials. Regarding these above, Chunfu Zhang’s team in our school carried out a wide range of work in tumor immunity regulation by nanomaterials.

At first, they developed a robust, dual drug-loaded, chemo-photothermal theranostic system based on SWNHs, termed SWNHs/C 18 PMH/mPEGPLA-DOX-Pt, for PAI-guided tumor therapy. By rationally engineering the surface of SWNHs with C 18 PMH and mPEG-PLA, DOX and cisplatin could be sequentially loaded onto the nanohorns with high efficiency and lack of interference and released in a pH-responsive, tandem, and sustainable manner. More significantly, SWNHs/C 18 PMH/mPEG-PLADOX-Pt demonstrated both dual drug chemotherapeutic and chemo-photothermal synergetic anti-tumor effects. As a result, tumor cells were completely ablated by chemo-photothermal therapy using relatively mild conditions. For solid tumor treatment, dual drug-loaded SWNHs exhibited prolonged blood circulation and could simultaneously and efficiently target both the primary tumors and their lung metastases. Consequently, chemo-photothermal treatment of primary tumors guided by PAI eradicated the primary and metastatic tumors. Our study demonstrates the considerable potential of SWNHs/C 18 PMH/mPEG-PLA-DOX-Pt for tumor chemo-photothermal combination therapy (Theranostics 2018, 8, 1966).

Furthermore, Gd³⁺ and chlorin e6 loaded single-walled carbon nanohorns (Gd-Ce6@SWNHs) are developed, and it was demonstrated that they were a strong immune adjuvant, and had high tumor targeting and penetration efficiency. Then, three in vivo mouse cancer models were established, and it was found that sequential PDT and PTT using Gd-Ce6@SWNHs synergistically promoted systemic antitumor immune responses, where PTT stimulated dendritic cells (DCs) to secrete IL-6 and TNF-