A Brain-Targeted DNA Delivery Nanocarrier Modulator for Synergistic Therapy of Parkinson's Disease.

The pathological characteristics of Parkinson's Disease (PD) are multifactorial, encompassing the aggregation of α-synuclein, mitochondrial dysfunction, and oxidative stress, necessitating the adoption of multitarget therapeutic strategies. In this study, a borneol-modified carboxymethyl chitosan nanoparticle system (BC/P/HCR NPs) was developed, aiming to codeliver curcumin, rosmarinic acid, and plasmid DNA (pDNA) targeting the SNCA gene for synergistic therapeutic intervention in PD. Borneol is capable of enhancing the permeability of the blood-brain barrier (BBB), while carboxymethyl chitosan contributes to improving the solubility of curcumin and preventing premature drug release. In a C57BL/6 mouse model of PD, BC/P/HCR NPs demonstrated enhanced penetration through the BBB, effectively alleviating motor dysfunction and reducing neuronal damage by downregulating the expression of α-synuclein, restoring mitochondrial function, and mitigating oxidative stress. These findings underscore the potential of BC/P/HCR NPs as a multifunctional nanotherapeutic platform for addressing the complex pathological features of PD.