Phototactic/Photosynthetic/Magnetic-Powered Chlamydomonas Reinhardtii-Metal-Organic Frameworks Micro/Nanomotors for Intelligent Thrombolytic Management and Ischemia Alleviation.

ABSTRACT

Thrombosis presents a critical health threat globally, with high mortality and incidence rates. Clinical treatment faces challenges such as low thrombolytic agent bioavailability, thrombosis recurrence, ischemic hypoxia damage, and neural degeneration. This study developed biocompatible Chlamydomonas Reinhardtii micromotors (CHL) with photo/magnetic capabilities to address these needs. These CHL micromotors, equipped with phototaxis and photosynthesis abilities, offer promising solutions. A core aspect of this innovation involves incorporating polysaccharides (glycol chitosan (GCS) and fucoidan (F)) into ferric Metal-organic frameworks (MOFs), loaded with urokinase (UK), and subsequently self-assembled onto the multimodal CHL, forming a core-shell microstructure (CHL@GCS/F-UK-MOF). Under light-navigation, CHL@GCS/F-UK-MOF is shown to penetrate thrombi, enhancing thrombolytic biodistribution. Combining CHL@GCS/F-UK-MOF with the magnetic hyperthermia technique achieves stimuli-responsive multiple-release, accelerating thrombolysis and rapidly restoring blocked blood vessels. Moreover, this approach attenuates thrombi-induced ischemic hypoxia disorder and tissue damage. The photosynthetic and magnetotherapeutic properties of CHL@GCS/F-UK-MOF, along with their protective effects, including reduced apoptosis, enhanced behavioral function, induced Heat Shock Protein (HSP), polarized M2 macrophages, and mitigated hypoxia, are confirmed through biochemical, microscopic, and behavioral assessments. This multifunctional biomimetic platform, integrating photo-magnetic techniques, offers a comprehensive approach to cardiovascular management, advancing related technologies.