Light-triggered photosynthetic engineered bacteria for enhanced-photodynamic therapy by relieving tumor hypoxic microenvironment.

Background: Singlet oxygen (1O2) has received considerable research attention in photodynamic therapy (PDT) due to its cytotoxic solid features. However, the inherent hypoxic state of the tumor microenvironment (TME) leads to the meager 1O2 quantum yield of inorganic PDT reagents, and their application in vivo remains elusive. Methods: We developed a novel strategy to fabricate active photosynthetic bacteria/photosensitizer/photothermal agent hybrids for photosynthetic tumor oxygenation and PDT and PTT tumor therapy under different laser irradiation sources. Photosynthetic bacteria combined with Ce6 photosensitizer and Au NPs photothermal agent, the obtained Bac@Au-Ce6 effectively targets tumor tissues and further enhances the tumor accumulation of Au-Ce6. Results: The results showed that the Au-Ce6-loaded engineered bacteria (Bac@Au-Ce6) maintained the photosynthetic properties of Syne. After i.v. injection, Bac@Au-Ce6 efficiently aggregates at tumor sites due to the tumor-targeting ability of active Syne. With 660 nm laser irradiation at the tumor site, the photoautotrophic Syne undergoes sustained photosynthetic O2 release and immediately activates O2 to 1O2 via a loaded photosensitizer. PTT was subsequently imparted by 808 laser irradiations to enhance tumor killing further. Conclusions: This work provides a new platform for engineering bacteria-mediated photosynthesis to promote PDT combined with PTT multi-faceted anti-tumor.

Live bio-nano-sonosensitizer targets malignant tumors in synergistic therapy.

Sonosensitizers that can increase the concentration of reactive oxygen species (ROS) within a tumor microenvironment is a high priority for sonodynamic therapy (SDT). In this study, a functionalized, smart nanosonosensitizer based on Au-RuO2 nanoparticles (NPs) and selenium nanoparticles (Se NPs) that were electrostatically self-assembled onto the surface of Listeria innocua (LI) was used to create Bac@ARS. Au NPs provided the core in which RuO2 was deposited to form Au-RuO2 NPs. Additionally, the underlying properties of the Au NPs and Se NPs were used to optimize the sonosensitivity performance. Compared with pristine RuO2 NPs, Bac@ARS exhibits highly efficient ROS-producing activity. Furthermore, Bac@ARS remodeled the hypoxic tumor microenvironment, enabling overproduction of ROS. Importantly, Bac@ARS exploits the natural tropism of LI to selectively accumulate in tumors, which improved the treatment precision at hypoxic tumor sites after sonodynamic activation. However, the activity of LI was greatly reduced after ultrasound (US) irradiation, ensuring the biosafety of Bac@ARS. Bac@ARS was also used to monitor tumors, in real time, using photoacoustic imaging of the gold-based nanoparticles. Therefore, Bac@ARS is a promising microbial sonosensitizer providing a new platform for the optimization of sonosensitizers for tumor treatment. STATEMENT OF SIGNIFICANCE: A bio-nano-sonosensitizer was designed using a Au nanoparticle (NP) core modified with RuO2 NPs. The Au-RuO2 NPs together with Se-NPs are attached via electrostatic adsorption to a live bacterium Listeria innocua (LI), creating Bac@ARS. The role of the NPs was to optimize the sonosensitivity performance at the target tumor site. Bac@ARS reshaped the tumor microenvironment and overcame tumor hypoxia leading to ROS overproduction. This activated a potent ICD-mediated cellular immunity and anti-tumor activity. Importantly, Bac@ARS exploited the natural tropism of LI to selectively accumulate in tumors, resulting in more precise delivery of the therapeutic effect while exhibiting reduced effects on healthy tissues.

EGCG-coated silver nanoparticles self-assemble with selenium nanowires for treatment of drug-resistant bacterial infections by generating ROS and disrupting biofilms.

Bacterial infections pose a serious threat to human health, and the development of new antibiotics has not kept pace with the development of bacterial resistance. Therefore, there is an urgent need to design antibiotic-like nano-formulations that break through bacterial resistance mechanisms. In this work, we successfully synthesized a safe and effective antibacterial nano-formulation of Se@Ag@EGCG by self-assembly of epigallocatechin gallate (EGCG)-coated silver nanoparticles (Ag) on the surface of selenium nanowires (Se). Thein vitrobacteriostatic results showed that 40µg ml-1Se@Ag@EGCG had significant antibacterial activity against drug-resistantStaphylococcus aureus(S. aureus) andEscherichia coli(E. coli) by destroying the formation of bacterial biofilm, promoting the production of high concentration reactive oxygen species and destroying bacterial cell wall. In addition, the results ofin vivoantibacterial experiments showed that subcutaneous administration of 10 mg kg-1of Se@Ag@EGCG could promote wound healing by reducing apoptosis and inflammatory responses in infected wounds. It is worth mentioning that the reduced and modified Se@Ag@EGCG by this natural product has negligiblein vivotoxicity. This development strategy of nano-antibacterial materials, which breaks through the drug resistance mechanism, provides new ideas for the development of drugs for drug-resistant bacterial infections.