Metal-Phenolic Network-Facilitated "Foe-to-Friend" Conversion of Melittin for Cancer Immunotherapy with Boosted Abscopal Effect.

As a naturally occurring cytolytic peptide, melittin (Mel) has strong cytolytic activity and is a potent therapeutic peptide for cancer therapy. However, the serious hemolytic activity of Mel largely impedes its clinical applications. In this work, based on the strong interactions between proteins/peptides and polyphenols, we develop a tannic acid-Fe3+ metal-phenolic network (MPN)-based strategy that can convert Mel from foe to friend via shielding its positive charges and reducing its hemolytic activity. Besides, an immune adjuvant resiquimod (R848) is also introduced for immunostimulation, affording the final Mel- and R848-coloaded nanodrug. The Mel-caused membrane disruption can induce immunogenic cell death for immunostimulation, R848 can act as an immune adjuvant to further facilitate the immunostimulatory effect, and the tannic acid-Fe3+ MPN-mediated Fenton reaction can produce reactive oxygen species for cancer treatment. Further experiments reveal that the nanodrug can effectively cause immunogenic cell death of tumor cells and arouse robust intratumoral and systemic antitumor immunostimulation. In the bilateral tumor-bearing mouse models, the nanodrug considerably destroys the primary tumor and also boosts the abscopal effect to ablate the distant tumor. Collectively, the MPN-facilitated "foe-to-friend" strategy may promote the practical applications of Mel and foster the development of cancer immunotherapeutics.

In situ generation of micrometer-sized tumor cell-derived vesicles as autologous cancer vaccines for boosting systemic immune responses.

Cancer vaccine, which can promote tumor-specific immunostimulation, is one of the most important immunotherapeutic strategies and holds tremendous potential for cancer treatment/prevention. Here, we prepare a series of nanoparticles composed of doxorubicin- and tyrosine kinase inhibitor-loaded and hyaluronic acid-coated dendritic polymers (termed HDDT nanoparticles) and find that the HDDT nanoparticles can convert various cancer cells to micrometer-sized vesicles (1.6-3.2 µm; termed HMVs) with ~100% cell-to-HMV conversion efficiency. We confirm in two tumor-bearing mouse models that the nanoparticles can restrain tumor growth, induce robust immunogenic cell death, and convert the primary tumor into an antigen depot by producing HMVs in situ to serve as personalized vaccines for cancer immunotherapy. Furthermore, the HDDT-healed mice show a strong immune memory effect and the HDDT treatment can realize long-term protection against tumor rechallenge. Collectively, the present work provides a general strategy for the preparation of tumor-associated antigen-containing vesicles and the development of personalized cancer vaccines.

Ultralight, Conductive Ti3C2Tx MXene/PEDOT:PSS Hybrid Aerogels for Electromagnetic Interference Shielding Dominated by the Absorption Mechanism.

MXene aerogels with a porous microstructure are a promising electromagnetic interference (EMI) shielding material due to its low density and excellent electrical conductivity, which has attracted widespread attention. Compared with traditional EMI shielding materials that rely on reflection as the primary mechanism, MXene aerogels with absorption as the dominant mechanism have greater potential for development as a novel EMI shielding material because of its ability to reduce environmental contamination from reflected electromagnetic (EM) waves from materials. In this study, a novel Ti3C2Tx MXene/PEDOT:PSS hybrid aerogel was presented by freeze-drying and thermal annealing using few-layered Ti3C2Tx MXene and the conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS). PEDOT:PSS not only improved the gelling ability of Ti3C2Tx but also successfully established a conductive bridge between MXene nanosheets. The experimental results demonstrated that the hybrid aerogel exhibited an obvious porous microstructure, which was beneficial for the multiple scattering of EM waves within the materials. The EMI shielding effectiveness and specific shielding effectiveness reached up to 59 dB and 10,841 dB·cm2·g-1, respectively, while the SER/SET ratio value was only 0.05, indicating superior wave absorption performance. Furthermore, the good impedance matching, due to the electrical conductance loss and polarization loss effect of the composites, plays a critical role in their excellent wave absorption and EMI shielding performance. Therefore, this work provides a practical approach for designing and fabricating lightweight absorption-dominated EMI shielding materials.

A Glucose/Oxygen-Exhausting Nanoreactor for Starvation- and Hypoxia-Activated Sustainable and Cascade Chemo-Chemodynamic Therapy.

Fenton reaction-mediated chemodynamic therapy (CDT) can kill cancer cells via the conversion of H2 O2 to highly toxic HO•. However, problems such as insufficient H2 O2 levels in the tumor tissue and low Fenton reaction efficiency severely limit the performance of CDT. Here, the prodrug tirapazamine (TPZ)-loaded human serum albumin (HSA)-glucose oxidase (GOx) mixture is prepared and modified with a metal-polyphenol network composed of ferric ions (Fe3+ ) and tannic acid (TA), to obtain a self-amplified nanoreactor termed HSA-GOx-TPZ-Fe3+ -TA (HGTFT) for sustainable and cascade cancer therapy with exogenous H2 O2 production and TA-accelerated Fe3+ /Fe2+ conversion. The HGTFT nanoreactor can efficiently convert oxygen into HO• for CDT, consume glucose for starvation therapy, and provide a hypoxic environment for TPZ radical-mediated chemotherapy. Besides, it is revealed that the nanoreactor can significantly elevate the intracellular reactive oxygen species content and hypoxia level, decrease the intracellular glutathione content, and release metal ions in the tumors for metal ion interference therapy (also termed "ion-interference therapy" or "metal ion therapy"). Further, the nanoreactor can also increase the tumor's hypoxia level and efficiently inhibit tumor growth. It is believed that this tumor microenvironment-regulable nanoreactor with sustainable and cascade anticancer performance and excellent biosafety represents an advance in nanomedicine.