Designing Selenium Nanoadjuvant as Universal Agent for Live-Killed Virus-Based Vaccine.

Inactivated virus vaccines with whole antigen spectra and good safety are the commonly used modality for preventing infections. However, the poor immunogenicity greatly limits its clinical applications. Herein, by taking advantages of the crucial roles of Se in the functions of immune cells and its biomineralization property, it successfully in-situ synthesized Se nanoadjuvant on inactivated viruses such as porcine epidemic diarrhea virus (PEDV), pseudorabies virus (PRV), and porcine reproductive and respiratory syndrome virus (PRRSV) in a facile method, which is universal to construct other inactivated virus vaccines. The nanovaccine can highly effectively enhance the uptake of PEDV/PRV/PRRSV into dendritic cells (DCs) and activate DCs via triggering TLR4 signaling pathways and regulating selenoproteins expressions. Furthermore, it exhibited better activities in triggering macrophages and natural killer cells-mediated innate immunity and T cells-mediated cellular immunity compared to PEDV and the commercial inactivated PEDV vaccine on both mice and swine models. This study provides a universal Se nanoadjuvant for developing inactivated viruses-based nanovaccines for preventing virus infections.

Metabolic Reprogramming of NK Cells by Black Phosphorus Quantum Dots Potentiates Cancer Immunotherapy.

Low persistence, metabolic dysfunction in microenvironment, and tumor-derived immunosuppression of Natural killer (NK) cells in patients are greatly limited the successful clinical application of NK cell-based cancer immunotherapy. Interestingly, herein that human serum albumin-encapsulated black phosphorus quantum dots (BPQDs@HSA) can effectively augment antitumor efficacy of clinical patients-derived NK cell immunotherapy is found. As the donor of phosphate group, BPQDs@HSA binds with the protein of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1A) and activates the downstream PI3K-Akt and mTOR signaling pathways to reprogram cell metabolism of glycolysis and further promote the oxidative phosphorylation, sequentially maintains the cell viability and immunity of NK cells. And multiomics analysis is therefore conducted to reveal the underlying immunoregulation mechanisms, and that BPQDs@HSA can interact with the Toll-like receptor (TLR) on the NK cell surface and increase the expression level of mTOR, and thus activate downstream NF-κB signalling pathways to regulate cytokine secretion and enhance immune tumoricidal is found. BPQDs@HSA can also enhance immune surveillance, relieve immune suppression, and inhibit tumor immune escape. Collectively, this study not only demonstrates a successful strategy for nanomedicine-potentiated immune-cancer therapy, but also sheds light on the understanding of interface between nanomedicine and immune cells activation.

Designing immunogenic nanotherapeutics for photothermal-triggered immunotherapy involving reprogramming immunosuppression and activating systemic antitumor responses.

Low tumor mutational burden and absence of T cells within the tumor sites are typical characteristics of "cold immune tumors" that paralyzes the immune system. The strategy of reversing "cold tumors" to "hot tumors" infiltrated high degree of T cells in order to activate anti-tumor immunity has attracted lots of attentions. Herein, immunogenic core-shell Au@Se NPs is fabricated by gold-selenium coordination bond to realize nanoparticles-mediated local photothermal-triggered immunotherapy. As expected, incorporation of gold nanostars (AuNSs) with improved photothermal stability and conversion efficiency promotes the disintegration and transformation of selenium nanoparticles (SeNPs), thus leading to enhanced cancer cells apoptosis by producing higher hyperthermia. Moreover, the results of in vivo experiments demonstrate that the synergy between SeNPs-mediated chemotherapy and AuNSs-induced photothermal therapy not only generated a localized antitumor-immune response with excellent cancer killing effect under the presence of tumor-associated antigens, but also effectively reprogrammed the tumor associated macrophages (TAMs) from M2 to M1 phenotype with tumoricidal activity to devour distant tumors. Without a doubt, this study not only provides a potent strategy to reverse the immunosuppressive tumor microenvironment, but also offers a new insight for potential clinical application in tumor immunotherapy.

Comparison of nanomedicine-based chemotherapy, photodynamic therapy and photothermal therapy using reduced graphene oxide for the model system.

Given the complexity of tumors, several nanomaterial-based treatment modalities like chemotherapy (CT), photodynamic therapy (PDT) and photothermal therapy (PTT) have been developed for combating cancers. However, it is still unclear which strategy is better or how to select optimal approaches for combination treatment since each strategy has been investigated under different conditions. Inspired by its good payload capacity and unique near-infrared absorption, reduced graphene oxide (rGO) was selected in this study as the carrier for loading of doxorubicin (DOX), a chemotherapy drug, and chlorin e6 (Ce6), a photosensitizer. The therapeutic efficacies of PTT, CT and PDT were systematically investigated in vitro using 2D culture and multicellular tumor spheroid (3D) models. Interestingly, while all three types of therapies delivered by rGO appeared to be effective in the conventional 2D cell culture model, only PTT but not CT and PDT showed great treatment efficacy in the 3D tumor spheroid model at the tested concentrations. Such a difference is due to the fact that heat diffusion is much more efficient than the diffusion of therapeutic molecules inside the tumor. Furthermore, in vivo evidence also confirmed the unique advantage of PTT compared to the other two treatment modalities using the TdT-mediated dUTP nick end labeling (TUNEL) staining assay. This study highlights the unique advantages of nanomedicine-based photothermal therapy among these three modalities in cancer treatment in terms of killing tumor cells located far from tumor blood vessels.

Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy.

A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.

Emerging nanomedicine approaches fighting tumor metastasis: animal models, metastasis-targeted drug delivery, phototherapy, and immunotherapy.

Metastasis is directly or indirectly responsible for the majority of cancer deaths. Anti-metastasis treatment is thus the key to cure cancer. Recent development in nanomedicine has shown great promise for tackling cancer metastasis. In recent years, nanoparticle-based drug delivery systems have been extensively explored for improving cancer treatment, showing the ability to reduce the risk of tumor metastasis compared with conventional chemotherapy. Photothermal therapy, by employing nano-theranostic agents, has also been found to be able to inhibit lymphatic tumor metastasis. Moreover, the post-immunological effects of certain types of nano-therapies may also be utilized to treat tumor metastasis, presenting an exciting new avenue towards successful cancer treatment. In this review article, we would like to summarize the latest research advances in the development of various emerging nanomedicine approaches for cancer metastasis treatment, and discuss future prospects in this emerging field as well as the clinical translation potential of these techniques.

Immunological responses triggered by photothermal therapy with carbon nanotubes in combination with anti-CTLA-4 therapy to inhibit cancer metastasis.

Photothermal ablation of primary tumors with single-walled carbon nanotubes is demonstrated to be able to trigger significant adaptive immune responses, which are not observed if tumors are removed by surgical resection. Such a treatment in combination with anti-CTLA-4 antibody therapy is able to prevent the development of tumor metastasis, which is a major cause of cancer death.