Nanomaterial combined engineered bacteria for intelligent tumor immunotherapy.

Cancer remains the leading cause of human death worldwide. Compared to traditional therapies, tumor immunotherapy has received a lot of attention and research focus due to its potential to activate both innate and adaptive immunity, low toxicity to normal tissue, and long-term immune activity. However, its clinical effectiveness and large-scale application are limited due to the immunosuppression microenvironment, lack of spatiotemporal control, expensive cost, and long manufacturing time. Recently, nanomaterial combined engineered bacteria have emerged as a promising solution to the challenges of tumor immunotherapy, which offers spatiotemporal control, reversal of immunosuppression, and scalable production. Therefore, we summarize the latest research on nanomaterial-assisted engineered bacteria for precise tumor immunotherapies, including the cross-talk of nanomaterials and bacteria as well as their application in different immunotherapies. In addition, we further discuss the advantages and challenges of nanomaterial-engineered bacteria and their future prospects, inspiring more novel and intelligent tumor immunotherapy.

Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy.

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Microfluidic Synthesis of CuH Nanoparticles for Antitumor Therapy through Hydrogen-Enhanced Apoptosis and Cuproptosis.

Cuproptosis has drawn enormous attention in antitumor material fields; however, the responsive activation of cuproptosis against tumors using nanomaterials with high atom utilization is still challenging. Herein, a copper-based nanoplatform consisting of acid-degradable copper hydride (CuH) nanoparticles was developed via a microfluidic synthesis. After coating with tumor-targeting hyaluronic acid (HA), the nanoplatform denoted as HA-CuH-PVP (HCP) shows conspicuous damage toward tumor cells by generating Cu+ and hydrogen (H2) simultaneously. Cu+ can induce apoptosis by relying on Fenton-like reactions and lead to cuproptosis by causing mitochondrial protein aggregation. Besides, the existence of H2 can enhance both cell death types by causing mitochondrial dysfunction and intracellular redox homeostatic disorders. In vivo experimental results further exhibit the desirable potential of HCP for killing tumor cells and inhibiting lung metastases, which will broaden the horizons of designing copper-based materials triggering apoptosis and cuproptosis for better antitumor efficacy.

Self-Metallized Whole Cell Vaccines Prepared by Microfluidics for Bioorthogonally Catalyzed Antitumor Immunotherapy.

Tumor whole cell, carrying a complete set of tumor-associated antigens and tumor-specific antigens, has shown great potential in the construction of tumor vaccines but is hindered by the complex engineering means and limited efficacy to cause immunity. Herein, we provided a strategy for the self-mineralization of autologous tumor cells with palladium ions in microfluidic droplets, which endowed the engineered cells with both immune and catalytic functions, to establish a bioorthogonally catalytic tumor whole-cell vaccine. This vaccine showed strong inhibition both in the occurrence and recurrence of tumor by invoking the immediate antitumor immunity and building a long-term immunity.

Silver-Modified Ba1-xCo0.7Fe0.2Nb0.1O3-δ Perovskite Performing as a Cathodic Catalyst of Intermediate-Temperature Solid Oxide Fuel Cells.

A series of silver (Ag)-modified barium cobalt ferrous niobate (Ba1-xCo0.7Fe0.2Nb0.1O3-δ, BCFN) materials were fabricated using a solid-state method by doping silver cations into the A-site of this perovskite matrix (Ag-BCFN). The electrochemical analyses indicated that the Ag-BCFN cathodic catalysts performed superior to the nonmodified catalysts when applied in intermediate-temperature solid oxide fuel cells (IT-SOFCs). These Ag-BCFN cathodic catalysts displayed a cubic perovskite structure (PDF 75-0227, Pm3̅m, α = 90°) with a high degree of crystallinity, as demonstrated by X-ray powder diffraction analyses. It was also found that the in situ exsolution of the silver ion (Ag+) occurred, where 57.9% of doped Ag+ was reduced into metallic Ag particles with size ranging from 5 to 10 nm, as shown by electron microscopic analyses. The cerium gadolinium oxide (Ce0.9Gd0.1O2-δ) electrolyte-supported symmetrical half cell using different Ag-BCFN formulations of Ba1-xAgxCo0.7Fe0.2Nb0.1O3-δ as electrodes showed a polarization resistance as low as 0.233 Ω·cm2 and an exchange current density of 85.336 mA·cm-2 at 650 °C under ambient pressure. The improved electrochemical kinetics is anticipated to be attributed to two reasons: doping of ions (Ag+) in the A-site of perovskite and in situ exsolved silver nanoparticles (Ag NPs) along the edge and on the surface of BCFNs improving the mobile charge and electrical properties of the material. The remaining Ag+ in the A-site induced the electron redistribution, whereas the Ag NPs were found to increase the electrochemically active sites and enable the formation of a triple-phase boundary. These explanations were confirmed by the density functional theory study, indicating that Ag-doping processes lead to a decrease in the formation energy of oxygen vacancies from 1.72 to 1.42 eV upon the partial substitution of Ba2+ by Ag+ cations.