Focused ultrasound-mediated cerium-based nanoreactor against Parkinson's disease via ROS regulation and microglia polarization.

Authors: Gao Y, Zhai L, Chen J, Lin D, Zhang LK, Yang H, Yang R, Mi L, Guan YQ

Neuronal damage caused by oxidative stress and inflammatory microenvironment dominated by microglia are the main obstacles in the treatment of Parkinson's disease (PD). In this study, we developed an integrated nanoreactor Q@CeBG by encapsulating CeO<sub>2</sub> nanozyme and quercetin (Que) into glutathione-modified bovine serum albumin, and then selected focused ultrasound (FUS) to temporarily open the blood-brain barrier (BBB) to enhance the accumulation level of Q@CeBG in the brain. Q@CeBG exhibited superior multi-ROS scavenging activity. Under the assistance of FUS, Q@CeBG nanoreactor can penetrate the BBB and act on neurons as well as microglia, reducing the neuron's oxidative stress level and polarizing microglia's phenotype from proinflammatory M1 to anti-inflammatory M2. In vitro and In vivo experiments demonstrated that Q@CeBG nanoreactor with good biocompatibility exhibit outstanding neuroprotection and immunomodulatory effects. In short, this dual synergetic nanoreactor will become a reliable platform against PD.

Introduction

Purpose Drug delivery with BBB opening

Study Objective To develop and evaluate a focused ultrasound-mediated cerium-based nanoreactor to treat Parkinson's disease by regulating reactive oxygen species and modulating microglia polarization.

Animal model / Human subject C57BL/6 J mice (male, 8-week-old, 22–26 g)

Disease model Parkinson's disease

Targeted brain region(s) Striatum

Cargo name and characteristics Q@CeBG nanoreactor (cerium oxide nanoparticle)

Route of administration Intravenous

Outcomes and Safety

Summary of Outcomes Focused ultrasound-delivered cerium-based nanoreactor reduced ROS, shifted microglia toward an anti-inflammatory (M2) phenotype, protected dopaminergic neurons, and improved motor function in Parkinson's disease models.

Duration of biological effect Not reported

Safety-related matter Hemolysis rate of both Q@CeBG and CeBG are <5% under 200 μM concentration, suggests the materials do not damage the erythrocyte membrane and suitable for intravenous delivery.

Brain Region

Ultrasound Parameters

FUS Frequency 1.0 MHz

FUS Intensity 1.5 W/cm^2

FUS Mode pulsed

Duration of a single FUS session 2 min, 1 min

Treatment frequency multiple sessions (5 times every 2 days over 7 days)

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