Pyroptosis is a lytic and inflammatory form of programmed cell death and could be induced by chemotherapy drugs via caspase-3 mediation. However, the key protein gasdermin E (GSDME, translated by the DFNA5 gene) during the caspase-3-mediated pyroptosis process is absent in most tumor cells because of the hypermethylation of DFNA5 (deafness autosomal dominant 5) gene. Here, we develop a strategy of combining decitabine (DAC) with chemotherapy nanodrugs to trigger pyroptosis of tumor cells by epigenetics, further enhancing the immunological effect of chemotherapy. DAC is pre-performed with specific tumor-bearing mice for demethylation of the DFNA5 gene in tumor cells. Subsequently, a commonly used tumor-targeting nanoliposome loaded with cisplatin (LipoDDP) is used to administrate drugs for activating the caspase-3 pathway in tumor cells and trigger pyroptosis. Experiments demonstrate that the reversal of GSDME silencing in tumor cells is achieved and facilitates the occurrence of pyroptosis. According to the anti-tumor activities, anti-metastasis results, and inhibition of recurrence, this pyroptosis-based chemotherapy strategy enhances immunological effects of chemotherapy and also provides an important insight into tumor immunotherapy.

Synthetic biology based on bacteria has been displayed in antitumor therapy and shown good performance. In this study, an engineered bacterium Escherichia coli MG1655 is designed with NDH‐2 enzyme (respiratory chain enzyme II) overexpression (Ec‐pE), which can colonize in tumor regions and increase localized H2O2 generation. Following from this, magnetic Fe3O4 nanoparticles are covalently linked to bacteria to act as a catalyst for a Fenton‐like reaction, which converts H2O2 to toxic hydroxyl radicals (•OH) for tumor therapy. In this constructed bioreactor, the Fenton‐like reaction occurs with sustainably synthesized H2O2 produced by engineered bacteria, and severe tumor apoptosis is induced via the produced toxic •OH. These results show that this bioreactor can achieve effective tumor colonization, and realize a self‐supplied therapeutic Fenton‐like reaction without additional H2O2 provision.

A photothermal bacterium (PTB) is reported for tumor‐targeted photothermal therapy (PTT) by using facultative anaerobic bacterium Shewanella oneidensis MR‐1 (S. oneidensis MR‐1) to biomineralize palladium nanoparticles (Pd NPs) on its surface without affecting bacterial activity. It is found that PTB possesses superior photothermal property in near infrared (NIR) regions, as well as preferential tumor‐targeting capacity. Zeolitic imidazole frameworks‐90 (ZIF‐90) encapsulating photosensitizer methylene blue (MB) are hybridized on the surface of living PTB to further enhance PTT efficacy. MB‐encapsulated ZIF‐90 (ZIF‐90/MB) can selectively release MB at mitochondria and cause mitochondrial dysfunction by producing singlet oxygen (1O2) under light illumination. Mitochondrial dysfunction further contributes to adenosine triphosphate (ATP) synthesis inhibition and heat shock proteins (HSPs) down‐regulated expression. The PTB‐based therapeutic platform of PTB@ZIF‐90/MB demonstrated here will find great potential to overcome the challenges of tumor targeting and tumor heat tolerance in PTT.

By leveraging the ability of Shewanella oneidensis MR-1 (S.oneidensis MR-1) to anaerobically catabolize lactate through the transfer of electrons to metal minerals for respiration, al actate-fueled biohybrid (Bac@MnO 2)w as constructed by modifying manganese dioxide (MnO 2)n anoflowers on the S. oneidensis MR-1 surface.T he biohybrid Bac@MnO 2 uses decorated MnO 2 nanoflowers as electron receptor and the tumor metabolite lactate as electron donor to make ac omplete bacterial respiration pathway at the tumor sites,which results in the continuous catabolism of intercellular lactate.A dditionally,d ecorated MnO 2 nanoflowers can also catalyze the conversion of endogenous hydrogen peroxide (H 2 O 2)into generate oxygen (O 2), which could prevent lactate production by downregulating hypoxia-inducible factor-1a (HIF-1a)e xpression. As lactate playsacritical role in tumor development, the biohybrid Bac@MnO 2 could significantly inhibit tumor progression by coupling bacteria respiration with tumor metabolism.

is generally treated with medication (2, 3-dimercaptosuccinic acid, DMSA or edetate calcium disodium, EDTA) [11] and hemodialysis [12] to eliminate internal lead ion in clinical, though these treatments are accompanied with inevitable nonselection, strong side effects, and high expenses. Worse still, there is no efficient precaution for chronic lead poisoning in lead exposure districts. [11][12][13] Consequently, it is quite necessary to develop a practical and economic therapy method for lead poisoning.Noteworthy, as the oldest living creature worldwide, bacteria present remarkable resistance to heavy metals in nature. [14][15][16] Profiting from diversified ingenious measures including adsorption, [17] ion exchange, [18] surface complexation, [16] and precipitation, [19,20] bacteria could survive in harsh environment with excess heavy metals, and further bioadsorb metal ions to reduce concentration level. Based on these, bacteria are regarded as highefficiency bioreactors to sequester metal ions from ppm to ppb levels mainly by bioadsorption. [17] Many nonpathogenic bacteria or probiotics have been widely modified by nanotechnology [21] or edited by synthetic biology [22][23][24][25] for disease treatment. Therein, modification of macromolecules inside biological contexts site-specifically and target-selectively through bioorthogonal reaction was successful without disturbing active life activities in biological systems. [26,27] Bio-orthogonal reaction was used to conjugate bacteria and inorganic nanoparticles through metabolic glycoengineering originated with unnatural sugars to construct a bioreactor for surface modification of bacteria. In comparison to conventional treatments, bacteria can accumulate to targeted organs with higher specificity, [28] lower systemic toxicity, and greater efficiency, [29] which means bacteria-based bioreactors could be an intelligent antidote in lead-enriched organs for lead poisoning. [30] Additionally, lead poisoning not merely causes direct damages, but also breaks the balance between the production of reactive oxygen species (ROS) and the generation of antioxidants. [3,13] The imbalance results in excessive oxidative stress accompanied by persistent lipid membrane damage. [31] Detoxification of reactive intermediates to reduce oxidative stress, further repair the resulting damage is as well as important.Here, we reported an integral biotic/abiotic hybrid bioreactor to integrate lead detoxification and ROS elimination, and to further achieve remission of lead injury. Briefly, a Multitudinous industrial products in daily life put human health at risk of heavy metal exposure, and natural bacteria have displayed superior performance in bioadsorption and biodegradation of heavy metal. In this study, a bacteria-based bioreactor is developed to precisely bioadsorb lead (Pb) ions, eliminate concomitant reactive oxygen species (ROS), and remit the injury of acute/chronic Pb poisoning. A nonpathogenic bacteria Escherichia coli MG1655 (Bac) is decorated with antioxidative cerium oxide...