Engineered NIR light-responsive bacteria as anti-tumor agent for targeted and precise cancer therapy

Pan, Huizhuo; Li, Lianyue; Pang, Gaoju; Han, Chien‐Chung; Liu, Baona; Zhang, Yingying; Shen, Yue; Sun, Tao; Liu, Jing; Chang, Jin; Wang, Hanjie

doi:10.1016/j.cej.2021.130842

Cited by 34 publications

(25 citation statements)

References 24 publications

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“…Alternatively, rare-earth upconversion materials can convert long wavelength NIR light to short wavelength visible light. As long wavelength light has been known to have stronger tissue-penetrating ability than visible light, the upconversion material is especially suitable for deep tissue application, which has been widely combined with traditional optogenetics operations for plenty of biological regulations. ,− Guided by this thinking, we attempted to use upconversion optogenetics to regulate deep tissue bacterial activity. The thulium (Tm)–coped–rod-shape upconversion material (UCR) has been successfully synthesized with a length around ∼1.5 μm, which emits ∼475 nm blue light upon excitation of 980 nm light (Figure a,b and Figure S2a).…”

Section: Resultsmentioning

confidence: 99%

Light-Sensitive Lactococcus lactis for Microbe–Gut–Brain Axis Regulating via Upconversion Optogenetic Micro-Nano System

et al. 2022

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The discovery of the gut–brain axis has proven that brain functions can be affected by the gut microbiota’s metabolites, so there are significant opportunities to explore new tools to regulate gut microbiota and thus work on the brain functions. Meanwhile, engineered bacteria as oral live biotherapeutic agents to regulate the host’s healthy homeostasis have attracted much attention in microbial therapy. However, whether this strategy is able to remotely regulate the host’s brain function in vivo has not been investigated. Here, we engineered three blue-light-responsive probiotics as oral live biotherapeutic agents. They are spatiotemporally delivered and controlled by the upconversion optogenetic micro–nano system. This micro–nano system promotes the small intestine targeting and production of the exogenous L. lactis in the intestines, which realizes precise manipulation of brain functions including anxiety behavior, Parkinson’s disease, and vagal afferent. The noninvasive and real-time probiotic intervention strategy makes the communiation from the gut to the host more controllable, which will enable the potential for engineered microbes accurately and effectively regulating a host’s health.

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Section: Resultsmentioning

confidence: 99%

Light-Sensitive Lactococcus lactis for Microbe–Gut–Brain Axis Regulating via Upconversion Optogenetic Micro-Nano System

et al. 2022

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“…Similarly, EL222 was used in Sinorhizobium meliloti (Pirhanov et al, 2021). Applications of none of these three optogenetic circuits are restricted to Gram-negative bacteria but extend to for instance bacilli e.g., B. subtilis (Castillo-Hair et al, 2019), and Lactococcus lactis (Pan et al, 2021;Pan et al, 2022;Zhang et al, 2021). While in most of these studies the optogenetic setups were used essentially unmodified, other reports required the optimization of plasmid backbones, promoters, ribosome-binding sites, and chromophore supply to elicit and boost light-dependent gene-expression responses (Castillo-Hair et al, 2019;Hueso-Gil et al, 2020).…”

Section: Applications Of Optogenetic Expression Control In Bacteriamentioning

confidence: 99%

“…The efficiency of the approach was at least partially ascribed to the synergistic activation of the immune system. Along similar lines, NIR light and UNPs activated the expression of the tumor necrosis factor α (TNF-α) from the EL222 circuit in E. coli Nissle (Pan et al, 2021). Bacteria harboring this optogenetic circuit were injected into the tail vein of mice together with the UNPs.…”

Section: Theranostics and Towards Biomedical Applicationsmentioning

confidence: 99%

Light-regulated gene expression in Bacteria: Fundamentals, advances, and perspectives

Ohlendorf

Möglich²

2022

Front. Bioeng. Biotechnol.

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Numerous photoreceptors and genetic circuits emerged over the past two decades and now enable the light-dependent i.e., optogenetic, regulation of gene expression in bacteria. Prompted by light cues in the near-ultraviolet to near-infrared region of the electromagnetic spectrum, gene expression can be up- or downregulated stringently, reversibly, non-invasively, and with precision in space and time. Here, we survey the underlying principles, available options, and prominent examples of optogenetically regulated gene expression in bacteria. While transcription initiation and elongation remain most important for optogenetic intervention, other processes e.g., translation and downstream events, were also rendered light-dependent. The optogenetic control of bacterial expression predominantly employs but three fundamental strategies: light-sensitive two-component systems, oligomerization reactions, and second-messenger signaling. Certain optogenetic circuits moved beyond the proof-of-principle and stood the test of practice. They enable unprecedented applications in three major areas. First, light-dependent expression underpins novel concepts and strategies for enhanced yields in microbial production processes. Second, light-responsive bacteria can be optogenetically stimulated while residing within the bodies of animals, thus prompting the secretion of compounds that grant health benefits to the animal host. Third, optogenetics allows the generation of precisely structured, novel biomaterials. These applications jointly testify to the maturity of the optogenetic approach and serve as blueprints bound to inspire and template innovative use cases of light-regulated gene expression in bacteria. Researchers pursuing these lines can choose from an ever-growing, versatile, and efficient toolkit of optogenetic circuits.

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“…FA@UCNP(l) was prepared according to the published paper in our laboratory . The particle size was measured by a DLS instrument (Malvern, Westborough MA, U.S.A.).…”

Section: Methodsmentioning

confidence: 99%

Upconversion Optogenetic Engineered Bacteria System for Time-Resolved Imaging Diagnosis and Light-Controlled Cancer Therapy

Zhang

Xue

Fang

et al. 2022

ACS Appl. Mater. Interfaces

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Engineering bacteria can achieve targeted and controllable cancer therapy using synthetic biology technology and the characteristics of tumor microenvironment. Besides, the accurate tumor diagnosis and visualization of the treatment process are also vital for bacterial therapy. In this paper, a light control engineered bacteria system based on upconversion nanoparticles (UCNP)-mediated time-resolved imaging (TRI) was constructed for colorectal cancer theranostic and therapy. UCNP with different luminous lifetimes were separately modified with the tumor targeting molecule (folic acid) or anaerobic bacteria (Nissle 1917, EcN) to realize the co-localization of tumor tissues, thus improving the diagnostic accuracy based on TRI. In addition, blue light was used to induce engineered bacteria (EcN-pDawn-φx174E/TRAIL) lysis and the release of tumor apoptosis-related inducing ligand (TRAIL), thus triggering tumor cell death. In vitro and in vivo results indicated that this system could achieve accurate tumor diagnosis and light-controlled cancer therapy. EcN-pDawn-φx174E/TRAIL with blue light irradiation could inhibit 53% of tumor growth in comparison to that without blue light irradiation (11.8%). We expect that this engineered bacteria system provides a new technology for intelligent bacterial therapy and the construction of cancer theranostics.

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Engineered NIR light-responsive bacteria as anti-tumor agent for targeted and precise cancer therapy

Cited by 34 publications

References 24 publications

Light-Sensitive Lactococcus lactis for Microbe–Gut–Brain Axis Regulating via Upconversion Optogenetic Micro-Nano System

Light-Sensitive Lactococcus lactis for Microbe–Gut–Brain Axis Regulating via Upconversion Optogenetic Micro-Nano System

Light-regulated gene expression in Bacteria: Fundamentals, advances, and perspectives

Upconversion Optogenetic Engineered Bacteria System for Time-Resolved Imaging Diagnosis and Light-Controlled Cancer Therapy

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