Synergistic Photothermal and Chemical Therapy by Smart Dual‐Functional Graphdiyne Nanosheets for Treatment of Parkinson's Disease

Abstract Successful treatment of Parkinson's disease (PD) is impeded by limited permeability of the blood brain barrier (BBB) which causes unsatisfactory drug accumulation in the central nervous system (CNS). In the present study, a novel 2D graphdiyne (GDY)‐based nanoplatform is utilized for the delivery of minocycline (MN), one drug candidate for PD treatment. These GDY nanosheets are prepared by sonication and exhibit excellent photothermal (PT) conversion ability (≈32%) without obvious toxicity in vitro. MN can be loaded onto GDY by π–π stacking (≈90%) and near infrared (NIR) irradiation is able to trigger the release of more than 30% of the payload. The BBB permeability of GDY is confirmed in both cellular and animal models. The behavioral defects of PD mice can be corrected after the PT and chemical synergistic treatment performed by GDY, with the dopaminergic neuron counting restored to normal level. Nanosheets‐mediated PT treatment exhibits comparable therapeutic effects to that of L‐DOPA, a commercialized PD drug. No obvious damage to major organs or circulation system is detected and physiological parameters remain stable during the behavioral study. This GDY‐based delivery system can serve as a promising platform for loading chemical drugs targeting neurodegenerative disorders.