Ultrasound-Switchable Nanozyme Augments Sonodynamic Therapy against Multidrug-Resistant Bacterial Infection

Abstract

Ultrasound (US)-driven sonodynamic therapy (SDT) has demonstrated wide application prospects in the eradication of deep-seated bacterial infections due to its noninvasiveness, site-confined irradiation, and high-tissue-penetrating capability. However, the ineffective accumulation of sonosensitizers at the infection site, the hypoxic microenvironment, as well as rapid depletion of oxygen during SDT greatly hamper the therapeutic efficacy of SDT. Herein, an US-switchable nanozyme system was proposed for the controllable generation of catalytic oxygen and sonosensitizer-mediated reactive oxygen species during ultrasound activation, thereby alleviating the hypoxia-associated barrier and augmenting SDT efficacy. This nanoplatform (Pd@Pt-T790) was easily prepared by bridging enzyme-catalytic Pd@Pt nanoplates with the organic sonosensitizer meso-tetra­(4-carboxyphenyl)­porphine (T790). It was really interesting to find that the modification of T790 onto Pd@Pt could significantly block the catalase-like activity of Pd@Pt, whereas upon US irradiation, the nanozyme activity was effectively recovered to catalyze the decomposition of endogenous H2O2 into O2. Such “blocking and activating” enzyme activity was particularly important for decreasing the potential toxicity and side effects of nanozymes on normal tissues and has potential to realize active, controllable, and disease-loci-specific nanozyme catalytic behavior. Taking advantage of this US-switchable enzyme activity, outstanding accumulation in infection sites, as well as excellent biocompatibility, the Pd@Pt-T790-based SDT nanosystem was successfully applied to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced myositis, and the sonodynamic therapeutic progression was noninvasively monitored by photoacoustic imaging and magnetic resonance imaging. The developed US-switchable nanoenzyme system provides a promising strategy for augmenting sonodynamic eradication of deep-seated bacterial infection actively, controllably, and precisely.

Ultrasound‐Activated Sensitizers and Applications

“…Sun et al. reported a significant decrease in the viability of cells treated with Pd@Pt‐T790 nanoplates under US irradiation, thereby indicating that hybridization of multiple materials can enhance SDT.…”

Recent Advances in Nanomaterial‐Assisted Combinational Sonodynamic Cancer Therapy

“…[ 103 ] Zheng's group prepared a Pd@Pt‐T790 nanoplatform for treating deep‐seated bacterial infections depending on nanozyme‐enhanced SDT (Figure 14B). [ 104 ] In this nanoplatform, they prepared the Pd@Pt catalase‐like nanozyme and then bridged the meso‐tetra(4‐carboxyphenyl)porphine (T790) organic sonosensitizer out of the nanozyme. Interestingly, the nanozyme activity of Pd@Pt was shown to be significantly blocked when coated with T790, and reinstated when treated with US irradiation.…”

“…Reproduced with permission. [ 104 ] Copyright 2020, American Chemical Society. C) Schematic diagram for the construction of TPZ@HHSN‐C/P‐mAb and its application for combined SDT with BRT.…”

The bright side of sound: perspectives on the biomedical application of sonoluminescence

“…61 Since then, it has been shown that SDT can treat solid tumours, 62-65 leukaemia 66 and atherosclerosis 67 and, moreover, remove proliferative scars and kill pathogenic microorganisms. 68,69 Since SDT was developed on the basis of PDT, some suggest that SDT shares a similar therapeutic mechanism where the ultrasonic wave triggers the sonosensitizer inside the target tissue, with production of ROS that kill the target cells. 70 Even though there is consensus in ROS production as the main cell killing mechanism, less is known about the mechanism underlying ROS production.…”