Ultrasound-Remote Selected Activation Mitophagy for Precise Treatment of Rheumatoid Arthritis by Two-Dimensional Piezoelectric Nanosheets

Abstract

Excess reactive oxygen species (ROS) produced by abnormal mitochondria is one of the critical triggers of rheumatoid arthritis (RA). Existing nanocatalytic therapies can only catalyze the breakdown of ROS but cannot address the root cause of ROS production, i.e., abnormal mitochondria. Here, we designed an ultrasound (US) piezoelectric catalytic therapy, which can induce mitophagy in a spatiotemporally controlled manner to treat RA. The prepared two-dimensional piezoelectric nanosheets (NSs) Fe/BiOCl with US catalytic activity can efficiently generate electrons under US stimulation to meet the purpose of consuming H + in the outer mitochondrial membrane and disturbing the H + supply in the mitochondrial matrix. This causes depolarization of the mitochondrial membrane potential (MMP), triggering the autophagy of mitochondria in regions of inflammation to eliminate the source of ROS regeneration. Analysis of cellular and RA model-related experiments showed that piezoelectric US-catalyzed therapy involving Fe/BiOCl NSs alleviated RA by inducing mitophagy. This provides an explanation of the mechanism for piezoelectric US catalytic therapy and suggests promising strategies for biomedical applications of US piezoelectric materials.

Redox Homeostasis Strategy for Inflammatory Macrophage Reprogramming in Rheumatoid Arthritis Based on Ceria Oxide Nanozyme-Complexed Biopolymeric Micelles

“…Notably, after 3 days of continuous incubation, Ce predominantly deposited in liver, spleen, and kidney of the mice (Figure S10B). The observations immediately suggested that Ce species released from decomposed micelles could be gradually excreted from the body after completing their anti-inflammatory functions and was also consistent with the excretion mechanisms of transitional metal species in previous reports, thus achieving balanced RA treatment efficacy and long-term safety. We also observed that mice in the HA@RH-CeO X group showed higher Ce deposition in their liver, spleen, and kidneys compared with the CeO X group (Figure S11F), showing their enhanced degradation and clearance capability.…”

Nanomedicine‐Enabled Sonomechanical, Sonopiezoelectric, Sonodynamic, and Sonothermal Therapy

“…[ 81 ] Furthermore, SPT could be used for rheumatoid arthritis (RA) treatment by Fe/BiOCl piezoelectric nanomaterial. [ 82 ]…”

“…Furthermore, SPT could be used for rheumatoid arthritis (RA) treatment by Fe/BiOCl piezoelectric nanomaterial. [82] Evidently, the nanomedicine-enabled SPT has vast application potential in several biomedical disciplines. Despite the accumulation of substantial evidence to date, the biological or physical mechanisms underlying them are still poorly understood, and their clinical translation has not yet been achieved.…”

Oxygen‐Vacancy‐Rich Piezoelectric BiO2−x Nanosheets for Augmented Piezocatalytic, Sonothermal, and Enzymatic Therapies

“…[13] In addition, US irradiation exhibited high tissue penetration (≈10 cm), targeted focus on deep tumors, and non-invasive nature, making it a potential candidate for an external activation source in medicine. [14] Currently, the exploration of therapeutic piezoelectric material is becoming a new research hotspot, while only several ones such as BaTiO 3 , [15] Bi 2 MoO 6 , [16] BiOCl, [17] NaNbO 3 , [18] and ZnO [19] have been reported. The reaction rates of some therapeutic piezoelectric catalysts still needs to be improved because the critical Gibbs free energy threshold obtained from periodic mechanical Scheme 1.…”

“…Currently, the exploration of therapeutic piezoelectric material is becoming a new research hotspot, while only several ones such as BaTiO 3 , [ 15 ] Bi 2 MoO 6 , [ 16 ] BiOCl, [ 17 ] NaNbO 3 , [ 18 ] and ZnO [ 19 ] have been reported. The reaction rates of some therapeutic piezoelectric catalysts still needs to be improved because the critical Gibbs free energy threshold obtained from periodic mechanical forces is not high enough to initiate redox reactions.…”