New progress has been made in developing targeted nano-platforms for Parkinson's disease therapy.
Professor Guan Yanqing's research team from South China Normal University published a paper titled “NIR-Assisted MgO-Based Polydopamine Nanoparticles for Targeted Treatment of Parkinson's Disease through the Blood–Brain Barrier” in the journal Advanced Healthcare Materials (IF=11.092, top journal in Q1).
In this research, Professor Guan Yanqing's research team used the AniView series multi-modal imaging system to capture the biological distribution of MgOp@PPLP in the PD model.
Parkinson's disease (PD) is one of the most common neurodegenerative diseases, which has seriously threatened human health. The pathology of PD is related to the degenerative loss of dopaminergic neurons in the substantia nigra compacta and a decrease in dopamine in the brain.
The mechanism of gene therapy is introducing therapeutic genes (DNA/RNA) or replacing, silencing, or correcting defective genes, providing a potential method to improve current therapy by preventing the loss of dopaminergic neurons. However, genetic drugs are easily degraded in the blood or cells, making it difficult to enter the cells. More importantly, the presence of the blood-brain barrier (BBB) prevents most drugs from entering the brain from the blood, which becomes the main obstacle in treating PD. Therefore, it is necessary to develop a new drug delivery platform that can both load genetic drugs into cells and penetrate the blood-brain barrier.
To overcome the current difficulties within gene therapy, the team developed a highly biocompatible method that combines non-invasive near-infrared radiation MgOp@PPLP Nano-platforms.
The nano-platform uses MgO nano-particles as the substrate and polydopamine as the shell, encapsulating the anti-SNCA plasmid inside, and modifying the surface with polyethylene glycol, lactoferrin, and puerarin to improve the hydrophilicity, brain targeting, and antioxidant properties of the particles, respectively.
Figure 1: Schematic diagram of MgOp@PPLP synthesis
MgOp@PPLP performs excellent near-infrared radiation (NIR) response. Guided by the photothermal effect, these MgOp@PPLP Particles can penetrate the blood-brain barrier and be absorbed by nerve cells, and play a role in gene therapy and antioxidant therapy. MgOp@PPLP performs good neuroprotective effects both in vivo and in vitro PD animal models.These results indicate that MgOp@PPLP Nano-platforms can be an ideal material for combating neurodegenerative diseases.
Figure 2: MgOp@PPLP Schematic diagram for treating PD
With the help of near-infrared radiation, MgOp@PPLP can reach the blood-brain barrier through blood circulation and penetrate it into nerve cells. Subsequently, NPs are transported to lysosomes, and after PDA shell disintegration, pDNA and Pue are released. pDNA can express siRNA, which is inhibited by SNCA mRNA degradation α-Syn expression. PDA and Pue can clear intracellular ROS, achieving the goal of protecting nerve cells and treating PD.
△ Figure 3: Image of the biological distribution of Cy5-NPs in brain A) and visceral B) The picture is capture by BLT Biotechnology AniView in vivo imaging system
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Reference
https://doi.org/10.1002/adhm.202201655