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Calcium phosphate engineered photosynthetic microalgae to combat hypoxic-tumor by in-situ modulating hypoxia and cascade radio-phototherapy.

ABSTRACT: Rationale: Hypoxia is one of the crucial restrictions in cancer radiotherapy (RT), which leads to the hypoxia-associated radioresistance of tumor cells and may result in the sharp decline in therapeutic efficacy. Methods: Herein, living photosynthetic microalgae (Chlorella vulgaris, C. vulgaris), were used as oxygenators, for in situ oxygen generation to relieve tumor hypoxia. We engineered the surface of C. vulgaris (CV) cells with calcium phosphate (CaP) shell by biomineralization, to form a biomimetic system (CV@CaP) for efficient tumor delivery and in-situ active photosynthetic oxygenation reaction in tumor. Results: After intravenous injection into tumor-bearing mice, CV@CaP could remarkably alleviate tumor hypoxia by continuous oxygen generation, thereby achieving enhanced radiotherapeutic effect. Furthermore, a cascade phototherapy could be fulfilled by the chlorophyll released from photosynthetic microalgae combined thermal effects under 650 nm laser irradiation. The feasibility of CV@CaP-mediated combinational treatment was finally validated in an orthotropic breast cancer mouse model, revealing its prominent anti-tumor and anti-metastasis efficacy in hypoxic-tumor management. More importantly, the engineered photosynthetic microalgae exhibited excellent fluorescence and photoacoustic imaging properties, allowing the self-monitoring of tumor therapy and tumor microenvironment. Conclusions: Our studies of this photosynthetic microsystem open up a new dimension for solving the radioresistance issue of hypoxic tumors.

SUBMITTER: Zhong D

PROVIDER: S-EPMC7914342 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Calcium phosphate engineered photosynthetic microalgae to combat hypoxic-tumor by in-situ modulating hypoxia and cascade radio-phototherapy.

Zhong Danni D Li Wanlin W Hua Shiyuan S Qi Yuchen Y Xie Tingting T Qiao Yue Y Zhou Min M

Theranostics 20210122 8

Rationale: Hypoxia is one of the crucial restrictions in cancer radiotherapy (RT), which leads to the hypoxia-associated radioresistance of tumor cells and may result in the sharp decline in therapeutic efficacy. Methods: Herein, living photosynthetic microalgae (Chlorella vulgaris, C. vulgaris), were used as oxygenators, for in situ oxygen generation to relieve tumor hypoxia. We engineered the surface of C. vulgaris (CV) cells with calcium phosphate (CaP) shel ...[more]

PMID: 33664849

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Project description:The global threat to public health posed by emerging multidrug-resistant bacteria in the past few years necessitates the development of novel approaches to combat bacterial infections. Endolysins encoded by bacterial viruses (or phages) represent one promising avenue of investigation. These enzyme-based antibacterials efficiently kill Gram-positive bacteria upon contact by specific cell wall hydrolysis. However, a major hurdle in their exploitation as antibacterials against Gram-negative pathogens is the impermeable lipopolysaccharide layer surrounding their cell wall. Therefore, we developed and optimized an approach to engineer these enzymes as outer membrane-penetrating endolysins (Artilysins), rendering them highly bactericidal against Gram-negative pathogens, including Pseudomonas aeruginosa and Acinetobacter baumannii. Artilysins combining a polycationic nonapeptide and a modular endolysin are able to kill these (multidrug-resistant) strains in vitro with a 4 to 5 log reduction within 30 min. We show that the activity of Artilysins can be further enhanced by the presence of a linker of increasing length between the peptide and endolysin or by a combination of both polycationic and hydrophobic/amphipathic peptides. Time-lapse microscopy confirmed the mode of action of polycationic Artilysins, showing that they pass the outer membrane to degrade the peptidoglycan with subsequent cell lysis. Artilysins are effective in vitro (human keratinocytes) and in vivo (Caenorhabditis elegans). Importance: Bacterial resistance to most commonly used antibiotics is a major challenge of the 21st century. Infections that cannot be treated by first-line antibiotics lead to increasing morbidity and mortality, while millions of dollars are spent each year by health care systems in trying to control antibiotic-resistant bacteria and to prevent cross-transmission of resistance. Endolysins--enzymes derived from bacterial viruses--represent a completely novel, promising class of antibacterials based on cell wall hydrolysis. Specifically, they are active against Gram-positive species, which lack a protective outer membrane and which have a low probability of resistance development. We modified endolysins by protein engineering to create Artilysins that are able to pass the outer membrane and become active against Pseudomonas aeruginosa and Acinetobacter baumannii, two of the most hazardous drug-resistant Gram-negative pathogens.

Dataset Information

Calcium phosphate engineered photosynthetic microalgae to combat hypoxic-tumor by in-situ modulating hypoxia and cascade radio-phototherapy.

Publications

Calcium phosphate engineered photosynthetic microalgae to combat hypoxic-tumor by <i>in-situ</i> modulating hypoxia and cascade radio-phototherapy.

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