In Situ Photocatalyzed Oxygen Generation with Photosynthetic Bacteria to Enable Robust Immunogenic Photodynamic Therapy in Triple‐Negative Breast Cancer

Abstract

Hypoxia in the tumor microenvironment is a major hurdle dampening the antitumor effect of photodynamic therapy (PDT). Herein, active photosynthetic bacteria (Synechococcus 7942, Syne) are utilized for tumor‐targeted photosensitizer delivery and in situ photocatalyzed oxygen generation to achieve photosynthesis‐boosted PDT. Photosensitizer‐encapsulated nanoparticles (HSA/ICG) are assembled by intermolecular disulfide crosslinking and attached to the surface of Syne with amide bonds to form a biomimetic system (S/HSA/ICG). S/HSA/ICG combined the photosynthetic capability of Syne and the theranostic effect of HSA/ICG. Syne capable of photoautotrophy exhibit a moderate immune stimulation effect and a certain photodynamic role under 660 nm laser irradiation. Upon intravenous injection into tumor‐bearing mice, S/HSA/ICG can effectively accumulate in tumors and generate oxygen continuously under laser irradiation through photosynthesis, which remarkably relieve tumor hypoxia and enhance reactive oxygen species production, thereby completely eliminating primary tumors. This photosynthesis‐boosted PDT can also effectively reverse the tumor immunosuppressive microenvironment and robustly evoke systematic antitumor immune responses, which exhibit excellent effect on preventing tumor recurrence and metastasis inhibition in a metastatic triple‐negative breast cancer mouse model. Hence, this photosynthetic bacteria‐based photosynthesis‐boosted immunogenic PDT offers a promising approach to eliminate both local and metastatic tumors.

Recent advances in innovative strategies for enhanced cancer photodynamic therapy

“…Reproduced with permission from Ref. 116 , Copyright © 2020, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Abbreviations: ICG: indocyanine green; PDT: photodynamic therapy; PA: photoacoustic.…”

“…The cascade process could produce large amounts of 1 O 2 to destroy cancer cells both in vitro and in vivo with a single-wavelength laser light source. Considering that photosynthetic bacteria ( Synechococcus 7942, Syne) possess stronger tumor targeting ability than Cyan, Liu et al 116 utilized Syne as the PS carrier and in situ photocatalyzed O 2 generation to realize photosynthesis-boosted PDT ( Figure 9 A ). ICG-encapsulated NPs (HSA/ICG) were assembled and then connected with the surface of Syne via amide bonds to form a PDT system (S/HSA/ICG).…”

Immunogenicity of Externally Activated Nanoparticles for Cancer Therapy

“…To overcome hypoxia, Liu et al [35] synthesized a biomimetic system composed of photosynthetic bacteria, Synechococcus 7942, bound to a photosensitizer, indocyanine green coated with human serum albumin. Once the bacteria infiltrated the tumor microenvironment, laser light was used to activate both the bacteria to produce oxygen and the photosensitizer to produce ROS.…”

“…A table summarizing types of nanoparticles vs triggers is shown in Table 1 which exhibits the role of nanoparticles in different systems. Ferrites [19,29,30], pure iron [31] Photodynamic therapy NIR Zinc phthalocyanine [33], indocyanine green [34], gold nanoparticle [35], chlorine e6 [20,21,29,38,41,42]…”

Peripheral RAFT Polymerization on a Covalent Organic Polymer with Enhanced Aqueous Compatibility for Controlled Generation of Singlet Oxygen

“…[1,9] To combat this issue, numerous approaches have been developed to enhance the efficiency of 1 O 2 generation such as the increase of the oxygen concentration with shuttles or the generation of oxygen in situ. [9,10] Among these efforts, nanoscale covalent organic polymers (COPs) or covalent organic frameworks (COFs) have emerged as materials of interest applied for enhanced photodynamic therapy owing to their porous structures and modular synthesis. [11] For instance, porphyrin and perfluoro have been used to construct COPs as oxygen nanoshuttles for improved tumor oxygenation and enhanced photodynamic therapy.…”