The Combination of Upconversion Nanoparticles and Photodynamic Therapy for Alzheimer’s Disease Treatment in Real-Time Monitoring

Abstract

Alzheimer’s Disease (AD) consumes many medical resources in disease caring and delays symptoms. The aggregation of amyloid-beta (Aβ) is regarded as one of the foci of AD. It will form oligomers and polymerize into fibrotic neurofibrillary tangles leading to AD. Many research has focused on the diagnosis and risk factors of Aβ aggregation, trying to reverse the situation of Aβ aggregation by various approaches. However, there are no advantageous solutions that have been developed so far. Establishing a system from monitoring to controlling Aβ aggregation is urgently needed as a new approach for AD treatment. Once Aβ aggregation can be monitored and controlled to oxide and degrade it before forming oligomers. It will bring huge benefits to AD treatment. Therefore, this study combines photodynamic therapy (PDT) and quartz crystal micro-scale (QCM) techniques to realize the degradation of Aβ and monitor whether Aβ is degraded, and establish a complete system.PDT has been applied in the medical field, especially for cancer treatment which induced oxidative stress results in different levels of protein oxidation. However, the limited excitation source limits the application of PDT, for example, the insufficient penetration depth of the excitation source prevents in vivo treatment of AD. Therefore, it needs to be combined with other materials to achieve in-depth treatment. This study proposes to modify photosensitizers on upconverting nanoparticles (UCNPs), and use 980 nm near-infrared to excite and then emit visible light to perform PDT. The combination of PDT and UCNPs generates the reactive oxygen species (ROS) to oxide Aβ and further degrade Aβ aggregation. However, most of the lanthanide metals and photosensitizers doped UCNPs are cytotoxic. Thus, Rose Bengal (RB) was selected as the reactive photosensitizer in this system owing to it being a metal-free, non-toxic, and widely available material. Also, it has been confirmed through research that RB can effectively transfer energy to form 1O2. To further ensure that material can be used in AD treatment, modify the SiO2 shell on the surface of UCNP to improve biocompatibility. The experimental results show that the cell survival rate can be maintained at about 80% when the concentration of UCNP reaches 25mg/mL.The degradation of the Aβ peptide can be monitored using the QCM technique. QCM was applied for monitoring the differences in the oscillation frequency by the degradation of the Aβ peptide attached to UCNPs. Meanwhile, the DCFH-DA ROS assay kit was applied to estimate the Aβ peptide oxidation level. The results of this study show that the combination of UCNPs for PDT can effectively oxidize and degrade Aβ, and utilizing QCM and ROS assay kit can monitor the level of Aβ oxidation and degradation in real-time. The establishment of this system can help more potential AD patients, providing a diagnostic and treatment method. Figure 1