Rationale: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world. Apart from traditional surgical resection, radiotherapy, and chemotherapy, more recent techniques such as nano-photothermal therapy and biotherapy are gradually being adopted for the treatment of HCC. This project intends to combine the advantages of nanoscale drug delivery systems with the targeting ability of CAR-T cells.

Tumor hypoxia compromises the effects of photodynamic therapy that consumes oxygen in the therapeutic process. Herein, a platinum (Pt)-carbon-integrated nanozyme with favorable catalase-like activity and photosensitizing properties was successfully constructed by immobilizing an ultrasmall Pt nanozyme into a MOF-derived carbon nanozyme through an in situ reduction strategy. The integration of a Pt nanozyme significantly improves the catalase activity of a carbon nanozyme that can effectively catalyze the decomposition of endogenous hydrogen peroxide to produce oxygen to improve the effects of photodynamic therapy. In addition, the integration of a Pt nanozyme also enhances the intrinsic photothermal performance of a carbon nanozyme. Combining the improved catalase-like activity with the enhanced photothermal properties together, the Pt-carbon nanozyme exhibits remarkable tumor inhibition ability in vivo. Thus, utilizing the enzymatic activity and photothermal/photosensitizing properties of nanozymes has great potential to overcome the limitations of traditional therapeutic strategies, and could inspire new directions for nanozyme-based biomedical applications.

Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much attention because of their excellent immune escapability; meanwhile, gold nanocages (AuNs) have been extensively used for cancer therapy due to their photothermal effect and drug delivery capability. The combination of the RBC membrane coating and AuNs may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we design erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy. First, anti-EpCam antibodies were used to modify the RBC membranes to target 4T1 cancer cells. Second, the antitumor drug paclitaxel (PTX) was encapsulated into AuNs. Then, the AuNs were coated with the modified RBC membranes. These new nanoparticles were termed EpCam–RPAuNs. We characterized the capability of the EpCam–RPAuNs for selective tumor targeting via exposure to near-infrared irradiation. The experimental results demonstrate that EpCam–RPAuNs can effectively generate hyperthermia and precisely deliver the antitumor drug PTX to targeted cells. We also validated the biocompatibility of the EpCam–RAuNs in vitro . By combining the molecularly modified targeting RBC membrane and AuNs, our approach provides a new way to design biomimetic nanoparticles to enhance the surface functionality of nanoparticles. We believe that EpCam–RPAuNs can be potentially applied for cancer diagnoses and therapies.