Catechol-Isolated Atomically Dispersed Nanocatalysts for Self-Motivated Cocatalytic Tumor Therapy.

Nanocatalytic tumor therapy based on Fenton nanocatalysts has attracted considerable attention because of its therapeutic specificity, enhanced outcomes, and high biocompatibility. Nevertheless, the rate-determining step in Fenton chemistry, which involves the transition of a high-valence metallic center (FeIII ) to a Fenton-active low-valence metallic center (FeII ), has hindered advances in nanocatalyst-based therapeutics. In this study, we constructed mesoporous single iron atomic nanocatalysts (mSAFe NCs) by employing catechols from dopamine to coordinate and isolate single iron atoms. The catechols also serve as reductive ligands, generating a field-effect-based cocatalytic system that instantly reduces FeIII species to FeII species within the mSAFe NCs. This self-motivated cocatalytic strategy enabled by mSAFe NCs accelerates the kinetics of the Fenton catalytic reaction, resulting in remarkable performance for nanocatalytic tumor therapy both in vitro and in vivo.

Photosynthetic Cyanobacteria-Hybridized Black Phosphorus Nanosheets for Enhanced Tumor Photodynamic Therapy.

Photodynamic therapy (PDT) has attracted tremendous attention due to its advantages such as high safety and effectiveness compared to traditional radiotherapy and chemotherapy. However, the intratumoral hypoxic microenvironment will inevitably compromise the PDT effect of the highly oxygen-dependent type II photosensitizers, implicating the urgent demand for continuous intratumoral oxygenation. Herein, biocompatible photosynthetic cyanobacteria have been modified with inorganic two-dimensional black phosphorus nanosheets (BPNSs) to be a novel bioreactor termed as Cyan@BPNSs. Upon 660 nm laser irradiation, the photosynthetic cyanobacteria generate oxygen continuously in situ through photosynthesis, followed by the photosensitization of BPNSs for activating oxygen into singlet oxygen (1 O2 ), resulting in a large amount of 1 O2 accumulation at the tumor site and the consequent strong tumor cell killing effect both in vitro and in vivo. This work provides an attractive strategy for efficient and biocompatible PDT, meanwhile extends the scope of microbiotic nanomedicine by hybridizing microorganisms with inorganic nanophotosensitizer.

Hybridized and engineered microbe for catalytic generation of peroxynitrite and cancer immunotherapy under sonopiezo initiation.

Living therapeutics is an emerging antitumor modality by living microorganisms capable of selective tropism and effective therapeutics. Nevertheless, primitive microbes could only present limited therapeutic functionalities against tumors. Hybridization of the microbes with multifunctional nanocatalysts is of great significance to achieve enhanced tumor catalytic therapy. In the present work, nitric oxide synthase (NOS)-engineered Escherichia coli strain MG1655 (NOBac) was used to hybridize with the sonopiezocatalytic BaTiO3 nanoparticles (BTO NPs) for efficient tumor-targeted accumulation and antitumor therapy. Under ultrasound irradiation, superoxide anions created by the piezocatalytic reaction of BTO NPs could immediately react with nitric oxide (NO) generated from NOBac to produce highly oxidative peroxynitrite ONOO- species in cascade, resulting in robust tumor piezocatalytic therapeutic efficacy, prompting prominent and sustained antitumoral immunoactivation simultaneously. The present work presents a promising cancer immunotherapy based on the engineered and hybridized microbes for highly selective and sonopiezo-controllable tumor catalytic therapy.

Genetically engineered probiotics as catalytic glucose depriver for tumor starvation therapy.

Cancer cells predominantly adapt the frequent but less efficient glycolytic process to produce ATPs rather than the highly efficient oxidative phosphorylation pathway. Such a regulated metabolic pattern in cancer cells offers promising therapeutic opportunities to kill tumors by glucose depletion or glycolysis blockade. In addition, to guarantee tumor-specific therapeutic targets, effective tumor-homing, accumulation, and retention strategies toward tumor regions should be elaborately designed. In the present work, genetically engineered tumor-targeting microbes (transgenic microorganism EcM-GDH (Escherichia coli MG1655) expressing exogenous glucose dehydrogenase (GDH) have been constructed to competitively deprive tumors of glucose nutrition for metabolic intervention and starvation therapy. Our results show that the engineered EcM-GDH can effectively deplete glucose and trigger pro-death autophagy and p53-initiated apoptosis in colorectal tumor cells/tissues both in vitro and in vivo. The present design illuminates the promising prospects for genetically engineered microbes in metabolic intervention therapeutics against malignant tumors based on catalytically nutrient deprivation, establishing an attractive probiotic therapeutic strategy with high effectiveness and biocompatibility.

Concurrent antibiosis and anti-inflammation against bacterial pneumonia by zinc hexacyanoferrate nanocatalysts.

The bacterial pneumonia has been demonstrated to cause acute and severe pathological lung injury as well as the uncontrollable oxidative cytokine storms. The effective therapeutics against bacterial pneumonia demands highly efficient pathogen elimination, oxidative stress alleviation and anti-inflammation. Nevertheless, current therapeutics fail to achieve these goals by a single medicine with satisfactory performance. Herein, we report a self-assembled zinc-doped prussian blue-analogue - zinc hexacyanoferrate nanocatalysts (ZnPBA NCs) possessing excellent broad-spectrum anti-bacterial activity and antioxidative catalytic activities against multiple reactive oxygen species (ROS) and the associated cytokine storm as well. By employing various oxidative substances and in vivo murine bacterial pneumoniae models, we verified that the synthetic zinc hexacyanoferrate nanocatalysts could concurrently eliminate the bacterial infection and largely alleviate infection-induced oxidative stress and inflammation, demonstrating the promising clinical application potentials against diverse bacterial infection-related diseases.