ROS‐Responsive Blended Nanoparticles: Cascade‐Amplifying Synergistic Effects of Sonochemotherapy with On‐demand Boosted Drug Release During SDT Process

Abstract

Sonodynamic therapy (SDT) not only has greater tissue‐penetrating depth compared to photo‐stimulated therapies, but also can also trigger rapid drug release to achieve synergistic sonochemotherapy. Here, reactive oxygen species (ROS)‐responsive IR780/PTL‐ nanoparticles (NPs) are designed by self‐assembly, which contain ROS‐cleavable thioketal linkers (TL) to promote paclitaxel (PTX) release during SDT. Under ultrasound (US) stimulation, IR780/PTL‐NPs produce high amounts of ROS, which not only induces apoptosis in human glioma (U87) cells but also boosts PTX released by decomposing the ROS‐sensitive TL. In the U87 tumor‐bearing mouse model, the IR780/PTL‐NPs releases the drug at the target sites in a controlled manner upon US irradiation, which significantly inhibits tumor growth and induces apoptosis in the tumor tissues with no obvious toxicity. Taken together, the IR780/PTL‐NPs are a novel platform for sonochemotherapy, and can control the spatio‐temporal release of chemotherapeutic drugs during SDT.

WITHDRAWN: Low-Intensity Pulsed Ultrasound-Generated Singlet Oxygen Induces Telomere Damage Leading to Glioma Stem Cell Awakening From Quiescence

“…As a novel noninvasive physical device, sonodynamic therapy can reversibly open the blood-brain barrier, enhance the delivery of drugs to the brain, and effectively kill tumors (27,28). In recent years, most researchers have focused on the thermal effect and cavitation of high-intensity focused ultrasound to inhibit the proliferation of cancer (29,30) and to enhance apoptosis when combined with chemotherapy agents (31,32). In contrast to the strong cytotoxicity of high-intensity focused ultrasound on tumors, LIPUS possesses the ability to promote fracture healing (12), accelerate regeneration (13), and to enhance thrombolysis (14) and nerve regeneration (15).…”

“…Meanwhile, the results of TUNEL and Ki67 staining also suggested that LIPUS enhanced the cytotoxicity of TMZ, promoted the apoptosis of tumor cells, and inhibited the proliferation of tumor cells. It is clear that LIPUS promoted the inhibitory effect of TMZ on the biological activity of tumor cells and enhanced the sensitivity of subcutaneous U87 transplanted tumors to TMZ in vivo (30). LIPUS, as a physical means, can provide new ideas for clinical solutions to postoperative chemotherapy-drug resistance, improve the e cacy of chemotherapy drugs, and reduce tumor recurrence (29,38,39).…”

Low-intensity pulsed ultrasound-generated singlet oxygen induces telomere damage leading to glioma stem cell awakening from quiescence

“…As a novel noninvasive physical device, sonodynamic therapy can reversibly open the blood-brain barrier, enhance the delivery of drugs to the brain, and effectively kill tumors (27,28). In recent years, most researchers have focused on the thermal effect and cavitation of high-intensity focused ultrasound to inhibit the proliferation of cancer (29,30) and to enhance apoptosis when combined with chemotherapy agents (31,32). In contrast to the strong cytotoxicity of high-intensity focused ultrasound on tumors, LIPUS possesses the ability to promote fracture healing (12), accelerate regeneration (13), and to enhance thrombolysis (14) and nerve regeneration (15).…”

Oxygen-Sufficient Nanoplatform for Chemo-Sonodynamic Therapy of Hypoxic Tumors

“…In the combination therapy between SDT and chemotherapy, ROS are generated under US irradiation, which can exert killing cell ability (Bai et al, 2012;Pan et al, 2018). With the help of US exposure, the release of a chemotherapeutic drug at the tumor would be promoted, and the chemo-drug resistance of cancer cells would be reversed (Wu et al, 2019). However, although in vivo results have shown a better therapeutic effect comparable to that of single therapy, hypoxia is still an obstacle that weakens the therapeutic efficacy (Shen et al, 2015;Wu et al, 2019).…”

“…With the help of US exposure, the release of a chemotherapeutic drug at the tumor would be promoted, and the chemo-drug resistance of cancer cells would be reversed (Wu et al, 2019). However, although in vivo results have shown a better therapeutic effect comparable to that of single therapy, hypoxia is still an obstacle that weakens the therapeutic efficacy (Shen et al, 2015;Wu et al, 2019). In this study, encouraged by the outstanding characteristic of PFTBA, we built an oxygen nanoplatform (PPID-NPs) to augment the efficacy of sonodynamic-chemotherapy against breast cancer.…”