Regulation of tumor hypoxic microenvironment by cyanobacteria-photosensitizer hybrid bioplatform for enhanced photodynamic therapy

Tumor hypoxic microenvironments limit the generation efficiency of reactive oxygen species (ROS) in photodynamic therapy (PDT) and exacerbate immune suppression, severely restricting its clinical efficacy. To overcome this bottleneck, this study developed a bio-organic hybrid delivery system based on oxygen-producing cyanobacteria and nano-photosensitizers (PCC7942@ICG-NPs), which synergistically enhances efficacy through in situ oxygen delivery and augment ROS. Specifically, indocyanine green (ICG) was loaded onto bovine serum albumin (BSA) via hydrophobic interactions to form stable nanoparticles (ICG-NPs), and the positively charged surface of the nanoparticles enabled efficient self-assembly with the oxygen-producing cyanobacterium PCC7942 by electrostatic interactions. Upon near-infrared laser activation, the cyanobacteria continuously release molecular oxygen through photosynthesis, significantly increasing the local tumor oxygen partial pressure (pO₂), which potentiates ICG-mediated photodynamic therapeutic efficacy and boosts ROS production, simultaneously improving the tumor hypoxic microenvironment and triggering systemic antitumor immunity. This work provides an innovative strategy to overcome tumor hypoxia and combined PDT therapy, showing significant clinical translation potential.