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.
A bacteria‐based photothermal therapeutic platform comprising PTB@ZIF‐90/MB is developed, which reveals great potential to augment photothermal therapy efficacy by tackling the challenges of tumor targeting and heat resistance.
Bacteria preferentially accumulating in tumor microenvironments can be utilized as natural vehicles for tumor targeting. However, neither current chemical nor genetic approaches alone can fully ...satisfy the requirements on both stability and high efficiency. Here, we propose a strategy of "charging" bacteria with a nano-photocatalyst to strengthen their metabolic activities. Carbon nitride (C
N
) is combined with Escherichia coli (E. coli) carrying nitric oxide (NO) generation enzymes for photo-controlled bacterial metabolite therapy (PMT). Under light irradiation, photoelectrons produced by C
N
can be transferred to E. coli to promote the enzymatic reduction of endogenous NO
to cytotoxic NO with a 37-fold increase. In a mouse model, C
N
loaded bacteria are perfectly accumulated throughout the tumor and the PMT treatment results in around 80% inhibition of tumor growth. Thus, synthetic materials-remodeled microorganism may be used to regulate focal microenvironments and increase therapeutic efficiency.
The unsatisfactory response rate of immune checkpoint blockade (ICB) immunotherapy severely limits its clinical application as a tumor therapy. Here, we generate a vaccine-based nanosystem by ...integrating siRNA for Cd274 into the commercial human papillomavirus (HPV) L1 (HPV16 L1) protein. This nanosystem has good biosafety and enhances the therapeutic response rate of anti-tumor immunotherapy. The HPV16 L1 protein activates innate immunity through the type I interferon pathway and exhibits an efficient anti-cancer effect when cooperating with ICB therapy. For both resectable and unresectable breast tumors, the nanosystem decreases 71% tumor recurrence and extends progression-free survival by 67%. Most importantly, the nanosystem successfully induces high response rates in various genetically modified breast cancer models with different antigen loads. The strong immune stimulation elicited by this vaccine-based nanosystem might constitute an approach to significantly improve current ICB immunotherapy.
Flexible in many aspects: inkjet printing of metal‐organic frameworks permits their larger area, high‐resolution deposition in any desired pattern, even in the form of gradients or shades. When ...flexible substrates are used, many applications can be envisioned, such as sensing and capture of hazardous gases for personal safety measures.
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, a lactate‐fueled ...biohybrid (Bac@MnO2) was constructed by modifying manganese dioxide (MnO2) nanoflowers on the S. oneidensis MR‐1 surface. The biohybrid Bac@MnO2 uses decorated MnO2 nanoflowers as electron receptor and the tumor metabolite lactate as electron donor to make a complete bacterial respiration pathway at the tumor sites, which results in the continuous catabolism of intercellular lactate. Additionally, decorated MnO2 nanoflowers can also catalyze the conversion of endogenous hydrogen peroxide (H2O2) into generate oxygen (O2), which could prevent lactate production by downregulating hypoxia‐inducible factor‐1α (HIF‐1α) expression. As lactate plays a critical role in tumor development, the biohybrid Bac@MnO2 could significantly inhibit tumor progression by coupling bacteria respiration with tumor metabolism.
MnO2 nanoflowers were modified on the cell surface of electrochemically active bacteria, S. oneidensis MR‐1. The biohybrids, which couple bacterial respiration with tumor metabolism, can catabolize intercellular lactate and prevent intracellular lactate production in the tumor, thereby inducing significant tumor inhibition.
Hypoxia, a typical feature of solid tumors, remarkably restricts the efficiency of photodynamic therapy (PDT). Here, a carbon nitride (C3N4)-based multifunctional nanocomposite (PCCN) for ...light-driven water splitting was used to solve this problem. Carbon dots were first doped with C3N4 to enhance its red region absorption because red light could be used to trigger the in vivo water splitting process. Then, a polymer containing a protoporphyrin photosensitizer, a polyethylene glycol segment, and a targeting Arg-Gly-Asp motif was synthesized and introduced to carbon-dot-doped C3N4 nanoparticles. In vitro study showed that PCCN, thus obtained, could increase the intracellular O2 concentration and improve the reactive oxygen species generation in both hypoxic and normoxic environments upon light irradiation. Cell viability assay demonstrated that PCCN fully reversed the hypoxia-triggered PDT resistance, presenting a satisfactory growth inhibition of cancer cells in an O2 concentration of 1%. In vivo experiments also indicated that PCCN had superior ability to overcome tumor hypoxia. The use of water splitting materials exhibited great potential to improve the intratumoral oxygen level and ultimately reverse the hypoxia-triggered PDT resistance and tumor metastasis.
Photothermal therapy (PTT) has drawn extensive research attention as a promising approach for tumor treatment. In this study, a bacteria‐assisted strategy relying on the selective reduction of ...perylene diimide derivative based supramolecular complex (CPPDI) to radical anions (RAs) by Escherichia coli in hypoxic tumors is developed to realize highly precise PTT of tumors. Noninvasive E. coli are first injected intravenously for selectively accumulating and replicating in the tumor due to the hypoxia tropism. Then, CPPDI is loaded in a peptide‐hybrid matrix metalloproteinase‐2 (MMP‐2) responsive liposome (MRL) and injected intravenously. After accumulated and released from MRL in the tumor where MMP‐2 is overexpressed, CPPDI is reduced by E. coli in the hypoxic tumor environment to produce CPPDI RAs (CRAs), which serve as effective photothermal agents for tumor cells thermal ablation under near‐infrared light irradiation. Since E. coli accumulate and grow in tumor sites selectively, this strategy accurately limits the production of CRAs in tumors for highly selective PTT, which will find great potential for precise tumor inhibition.
A bacteria‐assisted photothermal therapy is reported, to realize highly precise tumor treatment. The therapy relies on the selective reduction of perylene diimide derivative based supramolecular complex to radical anions by Escherichia coli in hypoxic tumors.
Discovering advanced materials for regulating cell death is of great importance in the development of anticancer therapy. Herein, by harnessing the recently discovered oxidative stress regulation ...ability of p53 and the Fenton reaction inducing capability of metal–organic network (MON), MON encapsulated with p53 plasmid (MON-p53) was designed to eradicate cancer cells via ferroptosis/apoptosis hybrid pathway. After confirming the detailed mechanism of MON-p53 in evoking ferroptosis, we further discovered that MON-p53 mediated a “bystander effect” to further sensitize cancer cells toward the MON-p53 induced ferroptosis. A 75-day anticancer experiment indicated that MON-p53 treatment not only suppressed the tumor growth but also prolonged the life-span of tumor bearing mice. Owing to its ability to promote intracellular oxidative stress, MON-p53 decreased the blood metastasis, lung metastasis, and liver metastasis. As a consequence, discovering methods to induce cell ferroptosis would provide a new insight in designing anticancer materials.
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 H
O
generation. Following from this, magnetic Fe
O
nanoparticles are covalently linked to bacteria to act as a catalyst for a Fenton-like reaction, which converts H
O
to toxic hydroxyl radicals (•OH) for tumor therapy. In this constructed bioreactor, the Fenton-like reaction occurs with sustainably synthesized H
O
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 H
O
provision.
To exchange information, recurrent mobility of population occurs among different communities in the network. Many researches have shown that spreading process of diseases is affected by the mobility ...dynamics of population. In this paper, we use the discrete-time Markov-chain approach to study the spreading process of diseases with recurrent population mobility. The epidemic threshold is given. We analyze some factors that affect the spreading of infectious diseases, including community size, mobility ratio, and the number of communities. The results show that a small-scale community structure, high mobility ratio of community population and a large number of temporal communities are conducive to preventing infectious diseases. As the infectious rate is close to 1, the fraction of infected individuals is only determined by the recovery rate. The numerical simulations further support our conclusions.
•A dynamic model is proposed to study the spreading of diseases with recurrent mobility of community population.•The epidemic threshold is given.•Many factors which affect the epidemic spreading are analyzed.
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