Defect Engineering Triggers Exceptional Sonodynamic Activity of Manganese Oxide Nanoparticles for Cancer Therapy

Abstract

Sonodynamic therapy (SDT) has received increasing interest in cancer treatment, but its clinical application is still constrained by the low activity of sonosensitizers and their unclear mechanism. Herein, a kind of oxygen-deficient manganese oxide (MnO x ) nanoparticles with greatly enhanced sonodynamic activity and good biocompatibility is developed as an advanced sonosensitizer. The introduced oxygen defects can remarkably enhance the electrical conductivity of manganese oxide (MnO) nanoparticles and serve as charge trapping sites to prohibit the electron−hole pair recombination upon ultrasound (US) irradiation. Such distinct merits promote the generation of reactive oxygen species (ROS), making MnO x as a decent sonosensitizer for SDT, and thus endowing MnO x with higher ROS production under US irradiation. As a demonstration, the MnO x nanoparticles decorated by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (MnO x -DSPE-PEG), a biocompatible coverage to enhance the dispersion ability, achieve a superior tumor killing efficiency of 96%, substantially higher than the MnO-DSPE-PEG counterpart (9%). Our experimental results also reveal that MnO x -DSPE-PEG nanoparticles induce the death of tumor cells by targeting polyunsaturated fatty acids in their membrane with US-triggered ROS. Furthermore, the as-designed sonosensitizers exhibit negligible toxicity toward the treated mice.

External physical field‐driven nanocatalytic cancer therapy

“…(1) Constructing vacancies in the sonosensitizers to inhibit electron-hole recombination. [74,75] 2b). [76] (2) Construction of heterostructures and modulation of the energy band structures to enhance ROS generation.…”

“…The acoustic power performance can be effectively enhanced through the rational design of modulated sonosensitizers. (1) Constructing vacancies in the sonosensitizers to inhibit electron‐hole recombination [74,75] . Yang et al.…”

Inorganic Sonosensitizers for Sonodynamic Therapy in Cancer Treatment

“…In a recent study, we prepared a deficient MnO x nanoparticle sonosensitizers by employing a high temperature (300 °C) treatment on MnO nanoparticles. [ 82 ] Afterward, 1,2‐distearoyl sn ‐glycero‐3‐phosphoethanolamine ‐N ‐[methoxy(polyethyleneglycol)‐2000] (DSPE‐PEG) modification was conducted to obtain MnO x ‐DSPE‐PEG, which enhanced the long term retention of nanoparticles in the tumor site. The presence of an oxygen defect on the MnO x not only could improve the conductivity, but also serve as a charge trap to limit the recombination of e − /h + pairs (Figure 12e,f).…”

“…f) The intrinsic mechanism of oxygen defect in MnO x for enhanced ROS generation. Reproduced wtih permission [82]. Copyright 2022, American Chemical Society.…”

Engineering Fe/Mn-doped zinc oxide nanosonosensitizers for ultrasound-activated and multiple ferroptosis-augmented nanodynamic tumor suppression

“…Remarkble advances in the field of nanotherapy have provided tremendous opportunities for human to fight against tumor [ [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] ]. Among all possible efforts made by reserachers, sonodynamic therapy (SDT) presents a promising cancer treatment modality because of its noninvasiveness and deep tissue penetration [ [15] , [16] , [17] , [18] , [19] ]. SDT employs ultrasound (US) to activate sonosensitizers for generating toxic reactive oxygen species (ROS), which further evokes apoptosis of tumor cells.…”