ROS-Triggered Self-Assembled Nanoparticles Based on a Chemo-Sonodynamic Combinational Therapy Strategy for the Noninvasive Elimination of Hypoxic Tumors

Abstract

The hypopermeability and hypoxia in the tumor milieu are important factors that limit multiple treatments. Herein, the reactive oxygen species (ROS)-triggered self-assembled nanoparticles (RP-NPs) was constructed. The natural small molecule Rhein (Rh) was encapsulated into RP-NPs as a sonosensitizer highly accumulated at the tumor site. Then highly tissue-permeable ultrasound (US) irradiation induced apoptosis of tumor cells through the excitation of Rh and acoustic cavitation, which prompted the rapid production of large amounts of ROS in the hypoxic tumor microenvironment. In addition, the thioketal bond structures in the innovatively designed prodrug LA-GEM were triggered and broken by ROS to achieve rapid targeted release of the gemcitabine (GEM). Sonodynamic therapy (SDT) increased the tissue permeability of solid tumors and actively disrupted redox homeostasis via mitochondrial pathways to kill hypoxic tumor cells, and the triggered response mechanism to GEM synergistically amplified the effect of chemotherapy. The chemo-sonodynamic combinational treatment approach is highly effective and noninvasive, with promising applications for hypoxic tumor elimination, such as in cervical cancer (CCa) patients who want to maintain their reproductive function.

Ultrasound-Controlled Prodrug Activation: Emerging Strategies in Polymer Mechanochemistry and Sonodynamic Therapy

“…The ROS-cleavable thioketal linker has also been employed by Wang and co-workers in a nanoparticle-based chemo-sonodynamic combinational therapy for the noninvasive elimination of hypoxic tumors (Figure a) . Rhein (a natural anthraquinone known for its sonosensitizing activity) and a thioketal-capped prodrug LA-GEM were encapsulated within lipid nanoparticles.…”

“…(b) The structure of an analogous nanoparticle comprising a ROS-activatable amphiphilic prodrug (PTX-TL-PEG1k-NH 2 ), a sonosensitizer (IR780), and a DSPE-based surfactant. Reproduced with permission from refs and . Copyright 2023, John Wiley and Sons.…”

Advances in Nanodynamic Therapy for Cancer Treatment

“…Following ultrasonic treatment, sonosensitizers undergo a transition from the ground state to an excited state. Subsequently, this excited state of the sonosensitizer can transfer energy to the surrounding molecular oxygen, resulting in the generation of ROS that target cancer cells, with the cavitation effect identified as the principal mechanism [79][80][81]. This phenomenon encompasses the formation, growth, and bursting of microbubbles (MBs), along with persistent oscillation.…”

An Injectable Black Phosphorus Hydrogel for Rapid Tooth Extraction Socket Healing

“…During the immediate postoperative period following tooth extraction, ROS are locally generated in the oral cavity and can enter the circulation . ROS, a battery of free radicals, such as singlet oxygen ( 1 O 2 ), , superoxide anion radical (•O 2 – ), , hydrogen peroxide (H 2 O 2 ), and hydroxyl radical (•OH). , The excess ROS existence in damaged sites may cause chronic healing, cell apoptosis and irreversible tissue injury . The production of ROS is a host defense mechanism of normal cell against bacterial pathogens .…”