Prevention of supercritical carbon dioxide fluid extract from Chrysanthemum indicum Linnén on cutaneous squamous cell carcinomas progression following UV irradiation in mice.

Chrysanthemum indicum Linnén (C. indicum), a medicinal and food herb with various bioactive components, may be of beneficial use in cosmetics and the treatment of skin-related diseases. However, to date, few studies have been reported on its potential preventive and therapeutic effects on skin cancer. Therefore, the present study aimed to investigate the effect and potential mechanism of action of supercritical carbon dioxide extract from C. indicum (CISCFE) on UV-induced skin cancer in a mouse model. Kunming mice were allocated randomly to five treatment groups: Sham, model, low concentration CISCFE, high concentration CISCFE and positive control nicotinamide groups. The dorsal skin of mice was irradiated with UV light for 31 weeks. Histopathological changes, ELISA assays, immunohistochemical analysis and western blotting were performed to investigate the potential therapeutic effects of CISCFE. The results showed that CISCFE alleviated skin oxidative and inflammatory damage in a UV-induced mouse model of skin cancer. Moreover, CISCFE suppressed abnormal activation of proto-oncogene c-Myc and the overexpression of Ki-67 and VEGF, and increased expression of the anti-oncogene PTEN, thereby reducing abnormal proliferation of the epidermis and blood vessels. Additionally, CISCFE increased the protein expression levels of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), Kelch-like ECH associated protein 1 (Keap1) and inhibited the expression of nuclear factor 2 erythroid 2-related factor 2 (Nrf2), phosphorylated (p)-p62 (Ser 349), p-p65 and acetyl-p65 proteins in a UV-induced skin cancer mouse model. In summary, CISCFE exhibited potent anti-skin cancer activity, which may be attributed its potential effects on the p62/Keap1-Nrf2 and SIRT1/NF-κB pathways.

Virus-Like Nanotherapeutic for Spatiotemporally Enhancing Antigen Presentation and Cross-Presentation toward Potential Personalized Immunotherapy.

One of the major causes of immunotherapy resistance is the loss of major histocompatibility complex class I (MHC-I) molecules in tumor cells or the downregulation of the class I antigen presentation pathway. In this study, a novel virus-like nanotherapeutic (siRNA@HCM) is developed via encapsulating nanosized siRNA nanoparticles in a hybrid membrane comprising a personalized tumor cell membrane and a universal 293T membrane expressing the mutant vesicular stomatitis virus glycoprotein (mVSV-G). Upon intravenous administration, siRNA@HCM accumulates at the tumor site and provides two potent driving forces for antitumor immunity. First, mVSV-G induces the fusion of siRNA@HCM with tumor cell membranes and directly injects siRNAs into the cytoplasm, significantly improving tumor intrinsic MHC-I antigen presentation. Moreover, mVSV-G can promote the maturation of dendritic cells, thereby achieving highly efficient antigen cross-presentation. The results demonstrate that spatiotemporally enhancing tumor intrinsic antigen presentation and cross-presentation via siRNA@HCM can achieve satisfactory antitumor efficacy and excellent biocompatibility. Immune infiltration analysis shows that siRNA@HCM treatment turns cold tumors into hot tumors. In addition, it significantly promotes the therapeutic effect of programmed death-1 inhibitor. In summary, virus-like nanotherapeutics present a promising approach to enhance the antitumor immune response, with distinct advantages for potential personalized therapy and clinical applications.

Constructing Spatiotemporally Controllable Biocatalytic Cascade in RBC Nanovesicles for Precise Tumor Therapy Based on Reversibly Induced Glucose Oxidase-Magnetoferritin Dimers.

Chemodynamic therapy is a promising tumor treatment strategy. However, it remains a great challenge to overcome the unavoidable off-target damage to normal tissues. In this work, it is discovered that magnetoferritin (M-HFn, biomimic peroxidase) can form nanocomplexes with glucose oxidase (GOD) in the presence of glucose, thus inhibiting the enzyme activity of GOD. Interestingly, GOD&M-HFn (G-M) nanocomplexes can dissociate under near-infrared (NIR) laser, reactivating the enzyme cascade. Based on this new finding, a spatiotemporally controllable biocatalytic cascade in red blood cell (RBC) nanovesicles (G-M@RBC-A) is fabricated for precise tumor therapy, which in situ inhibits enzyme cascade between GOD and M-HFn during blood circulation and reactivates the cascade activity in tumor site by NIR laser irradiation. In RBC nanovesicles, GOD is grabbed by M-HFn to form G-M nanocomplexes in the presence of glucose, thus inhibiting the Fenton reaction and reducing side effects. However, after NIR laser irradiation, G-M nanocomplexes are spatiotemporally dissociated and the cascade activity is reactivated in the tumor site, initiating reactive oxygen species damage to cancer cells in vivo. Therefore, this work provides new insight into the fabrication of spatiotemporally controllable biocatalytic cascade for precise cancer therapy in the future.