Cellular vesicle–electrically conducting polymer integrating with microalgae attenuate retinal inflammation associated with IL-6, immunomodulation, and pro-inflammatory cytokines in diabetes-related retinal disease

Diabetes-related retinal disease (DR) remains a leading cause of vision loss and is driven by a pathological retinal microenvironment marked by M1-skewed macrophage polarization, excessive reactive oxygen species (ROS), and oxidative stress. Herein, we bioengineered a microalgae-based therapeutic delivery system—microalgae C. reinhardtii @ electrically conducting polymer(ECP)/protamine(PRT)/platelet-derived vesicles—designed for intranasal administration to target retinal lesions. Under wireless 660-nm near-infrared light activation, the platform leverages the photosynthetic properties of microalgae to generate a multi-pronged therapeutic response. This mechanism affords robust immunomodulation and anti-inflammatory effects while offering biomimetic functionality. In vitro, the formulation exhibited excellent biocompatibility and protected retinal ganglion cells by markedly attenuating oxidative stress and suppressing the release of pro-inflammatory cytokines. In a streptozotocin (STZ)-induced DR model, intranasal administration significantly promoted immune regulation, with no detectable toxicity in the eyes or major organs. Collectively, this cascade strategy—integrating microenvironment normalization, immune modulation, and anti-inflammatory action—shows strong potential for DR therapy and supports future clinical translation.