Using near-infrared enhanced thermozyme and scFv dual-conjugated Au nanorods for detection and targeted photothermal treatment of Alzheimer's disease

Investigation of targeting inhibitors of A beta aggregation, heme-A beta peroxidase-like activity and efficient detectors of A beta aggregation, are of therapeutic value and diagnostics significance for the treatment of Alzheimer's disease (AD). Due to the complex pathogenesis of AD, theranostics treatment with multiple functions are necessary. Herein we constructed the NIR absorption property of gold nanorods (GNRs) loaded with single chain variable fragment (scFv) 12B4 and thermophilic acylpeptide hydrolase (APH) ST0779 as a smart theranostic complex (GNRs-APH-scFv, GAS), which possesses both rapid detection of A beta aggregates and NIR photothermal treatment that effectively disassembles A beta aggregates and inhibits A beta-mediated toxicity. Methods: We screened targeting anti-A beta scFv 12B4 and thermophilic acylpeptide hydrolase as amyloid-degrading enzyme, synthesized GAS gold nanorods complex. The GAS was evalued by A beta inhibition and disaggregation assays, A beta detection assays, A beta mediated toxicity assays in vitro. In vivo, delaying A beta-induced paralysis in AD model of Caenorhabditis elegans was also tested by GAS. Results: In vitro, GAS has a synergistic effect to inhibit and disassociate A beta aggregates, in addition to decrease heme-A beta peroxidase-like activity. In cultured cells, treatment with GAS reduces A beta-induced cytotoxicity, while also delaying A beta-mediated paralysis in CL4176 C. elegans model of AD. Furthermore, the photothermal effect of the GAS upon NIR laser irradiation not only helps disassociate the A beta aggregates but also boosts APH activity to clear A beta. The GAS, as a targeting detector and inhibitor, allows real-time detection of A beta aggregates. Conclusion: These results firstly highlight the combination of scFv, APH and nanoparticles to be theranostic AD drugs. Taken together, our strategy provides a new thought into the design of smart compounds for use as efficiently therapeutic and preventive agents against AD. Moreover, our design provides broad prospects of biomedical strategy for further theranostics application in those diseases caused by abnormal protein.