Photosynthetic Bacteria: Light-Responsive Biomaterials for Anti-Tumor Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is a promising noninvasive tumor treatment modality that relies on generating reactive oxygen species (ROS) and requires an adequate oxygen supply to the target tissue. However, hypoxia is a common feature of solid tumors and profoundly restricts the anti-tumor efficacy of PDT. In recent years, scholars have focused on exploring nanomaterial-based strategies for oxygen supplementation and integrating non-oxygen-consuming treatment approaches to overcome the hypoxic limitations of PDT. Some scholars have harnessed the photosynthetic oxygen production of cyanobacteria under light irradiation to overcome tumor hypoxia and engineered them as carriers of photosensitizers instead of inorganic nanomaterials, resulting in photosynthetic bacteria (PSB) attracting significant attention. Recent studies have shown that light-triggered PSB can exhibit additional properties, such as photosynthetic hydrogen production, ROS generation, and photothermal conversion, facilitating their use as promising light-responsive biomaterials for enhancing the anti-tumor efficacy of PDT. Therefore, understanding PSB can provide new insights and ideas for future research. This review mainly introduces the characteristics of PSB and recent research on light-triggered PSB in anti-tumor PDT to enrich our knowledge in this area. Finally, the challenges and prospects of using PSB to enhance the anti-tumor efficacy of PDT were also discussed.

Keywords: PDT; PTT; cyanobacteria; hypoxia; photosynthetic bacteria; purple bacteria.

Figure 1

Schematic representation of photosynthetic oxygen production and hydrogen production in PSB.

Figure 2

(A) Schematic illustration of the synthesis and and mechanism of ceCyan. Reproduced from Huo M, Wang L, Zhang L, Wei C, Chen Y et al. Photosynthetic Tumor Oxygenation by Photosensitizer-Containing Cyanobacteria for Enhanced Photodynamic Therapy. Angew Chem Int Ed Engl. 2020; 59: 1906–1913. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (B) Schematic illustration of the synthesis and and mechanism of UR-Cyan cells. Reproduced from Huo M, Liu P, Zhang L, Wei C, Wang L et al. Upconversion Nanoparticles Hybridized Cyanobacterial Cells for Near-Infrared Mediated Photosynthesis and Enhanced Photodynamic Therapy. Advanced Functional Materials. 2021; 31: 2,010,196. © 2021 Wiley-VCH GmbH.

Figure 3

(A) Schematic illustration of the synthesis and mechanism of UCNPs/S7942/RB-RHY. Reprinted from Colloids Surf B Biointerfaces. Volume 201, Zhang X, Zhang Y, Zhang C, Yang C, Tian R et al. An injectable hydrogel co-loading with cyanobacteria and upconversion nanoparticles for enhanced photodynamic tumor therapy. 111640, Copyright 2021, with permission from Elsevier. (B) Schematic illustration of the synthesis and animal experiments of ALG-MI-S2973, and tumor growth curves of tumor-bearing mice with different treatments (**P < 0.01 compared with untreated group). Reproduced from Sun T, Zhang Y, Zhang C et al. Cyanobacteria-Based Bio-Oxygen Pump Promoting Hypoxia-Resistant Photodynamic Therapy. Front Bioeng Biotechnol. 2020; 8: 237. Creative Commons.

Figure 4

(A) Schematic illustration of the synthesis and mechanism of Bac@Au-Ce6, and transmission electron microscope (TEM) images of Au NPs, Au-Ce6, and Bac@Au-Ce6. Reproduced Yin C, Wang Z, Dai C et al. Light-triggered photosynthetic engineered bacteria for enhanced-photodynamic therapy by relieving tumor hypoxic microenvironment. Theranostics. 2023; 13:1632–1648. Creative Commons. (B) Schematic illustration of the synthesis and mechanism of Cyan@BPNSs. Reproduced from Qi F, Ji P, Chen Z, Wang L, Yao H et al. Photosynthetic Cyanobacteria-Hybridized Black Phosphorus Nanosheets for Enhanced Tumor Photodynamic Therapy. Small. 2021; 17: e2102113. © 2021 Wiley-VCH GmbH. (C) Schematic illustration of the synthesis and mechanism of SpiD. Reproduced with permission from An X, Zhong D, Wu W, Wang R, Yang L et al. Doxorubicin-Loaded Microalgal Delivery System for Combined Chemotherapy and Enhanced Photodynamic Therapy of Osteosarcoma. ACS Appl Mater Interfaces. 2024; 16: 6868–6878. Copyright © 2024 American Chemical Society.