In situ dual-activated NIRF/PA carrier-free nanoprobe for diagnosis and treatment of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease threatening the life of millions people worldwide. Oxidative stress, mitochondrial dysfunction, and neuroinflammation are the pivotal causative elements of PD. Precise diagnosis enables timely monitoring initiation and progression of PD, thereby facilitating the formulation of customized and targeted treatment strategies. Optical imaging offers one alternative way for PD diagnosis. However, available diagnostic probes suffer from the inability to bypass the blood brain barrier (BBB). To accurately diagnose and effectively combat PD, there is an urgent need to develop an integrated diagnostic and therapeutic nanoprobe that can bypass the BBB and target the factors underlying degeneration of dopaminergic (DA) neurons. In present study, one integrated carrier-free nanoprobe HVCur-NPs towards those factors was designed and constructed. By modifying probe side chain with polypeptide, RVG29, we obtained brain-targeting HV-PEG-RVG29. It not only enables BBB penetration, but also produces near-infrared fluorescence (NIRF) and photoacoustic (PA) signals in cascade response to H2O2 and viscosity. The release of loaded curcumin (CUR) prevents oxidative stress, neuroinflammation and restore mitochondrial function so as to rescue PD phenotypes. In cellular PD model, HVCur-NPs generated NIRF/PA signals in response to elevated ROS and viscosity, and ameliorated cell apoptosis by eliminating ROS and restoring mitochondria function. Moreover, in mice PD model, HVCur-NPs realized in situ NIRF/PA imaging brain, and rescued DA neuron loss and restored the behavioral deficit of PD mice, without detectable biotoxicity. This carrier-free nanoprobe opens venues for integrated diagnosis and treatment of neurodegenerative diseases.