Photosynthetic Tumor Oxygenation by Photosensitizer‐Containing Cyanobacteria for Enhanced Photodynamic Therapy

Abstract

Sustained tumor oxygenation is of critical importance during type‐II photodynamic therapy (PDT), which depends on the intratumoral oxygen level for the generation of reactive oxygen species. Herein, the modification of photosynthetic cyanobacteria with the photosensitizer chlorin e6 (ce6) to form ce6‐integrated photosensitive cells, termed ceCyan, is reported. Upon 660 nm laser irradiation, sustained photosynthetic O2 evolution by the cyanobacteria and the immediate generation of reactive singlet oxygen species (1O2) by the integrated photosensitizer could be almost simultaneously achieved for tumor therapy using type‐II PDT both in vitro and in vivo. This work contributes a conceptual while practical paradigm for biocompatible and effective PDT using hybrid microorganisms, displaying a bright future in clinical PDT by microbiotic nanomedicine.

Development of a Novel Perfusable Solution for ex vivo Preservation: Towards Photosynthetic Oxygenation for Organ Transplantation

“…Based on this, photosynthetic therapies aim to generate a local symbiotic relationship between animal and photosynthetic cells where, in the presence of light, both metabolisms could be coupled with each other ( Chávez et al, 2020 ). This approach has been described by our group in recent in vitro ( Hopfner et al, 2014 ; Centeno-Cerdas et al, 2018 ; Chávez et al, 2021 ) and in vivo ( Schenck et al, 2015 ; Chávez et al, 2016 ) studies, and further confirmed by other independent groups, highlighting its potential application in several medical fields, including tissue engineering and regeneration ( Yamaoka et al, 2012 ; Evron et al, 2015 ; Haraguchi et al, 2017 ; Chen et al, 2020 ), heart ischemia ( Cohen et al, 2017 ), and tumor treatment ( Huo et al, 2020 ; Liu et al, 2020 ; Qiao et al, 2020 ). Moreover, an ongoing clinical trial is confirming its safety for tissue regeneration in humans ( Obaíd et al (2021) accepted for publication.…”

Oxygen Pathology and Oxygen-Functional Materials for Therapeutics

“…This paradigm provides a promising strategy for employing biocompatible photosynthetic microorganisms to treat a variety of oxygen-deficient pathologies. 96 Another interesting design concept arises from the PLANT (photosynthetic leaf-inspired abiotic/biotic nanothylakoid) system generated from vegetables (e.g., spinach, lettuce, and cabbage) ( Figure 7H). 97 The isolated thylakoid from the spinach remains active in oxygen generation upon 660-nm laser irradiation ( Figure 7I), which may provide a promising opportunity to normalize the tumor microenvironment by suppressing anaerobic respiration (Figure 7J), HIF-1a expression ( Figure 7K), and the angiogenesis outcome.…”

“…(E) Schematic illustration of the paradigm of photosynthesis-enhanced photodynamics. Reprinted with permission from Huo et al 96 generated inside the neutrophils as a potent substance to engulf foreign microorganisms. The nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidases [NOXs]) can actively convert oxygen into superoxide anions ( Figures 8C), 102 followed by the subsequent catalysis by SOD and myeloperoxidase (MPO).…”

Persistent luminescence phosphor as in-vivo light source for tumoral cyanobacterial photosynthetic oxygenation and photodynamic therapy

“…Recently, light-triggered biosynthesis as a prospective oxygen-generating modality has been employed for the normalization the tumor microenvironment [ 23 ]. As a victorious paradigm, engineering construction of photosynthetic bacteria, such as red blood cell membrane-algae [ 24 ], Ce6-cyanobacterial cells [ 25 ], indocyanine green-cyanobacteria biomimetic system [ 26 ], and Chlorella-based oxygen-affording engines [ 27 ] exhibits the intriguing PDT performance due to adequate supply of exogenous oxygen and inherent tumor-targeting property of bacteria.…”