Tumor ablation using low-intensity ultrasound and sound excitable drug

Abstract

The cell membrane is a semi-fluid container that defines the boundary of cells, and provides an enclosed environment for vital biological processes. A sound excitable drug (SED) that is non-cytotoxic to cells is developed to disrupt the plasma membrane under gentle ultrasound insonation, 1 MHz, 1 W/cm2. The frequency and power density of insonation are within the physical therapy and medical imaging windows; thus the applied ultrasound is safe and not harmful to tissues. The insertion of SEDs into the plasma membrane is not toxic to cells; however, the intruding SEDs weaken the membrane’s integrity. Under insonation, the ultrasound energy destabilized the SED disrupted membranes, resulting in membrane rupture and eventual cell death. In a xenograft breast tumor model, the SED alone or the ultrasound alone caused little adverse effects to tumor tissue, while the combined treatment triggered necrosis with a brief local insonation of 3 minutes. The described sono-membrane rupture therapy could be a safe alternative to the currently used high-energy tissue ablation technology, which uses X-rays, gamma rays, electron beams, protons, or high- intensity focused ultrasound.

Phorbiplatin, a Highly Potent Pt(IV) Antitumor Prodrug That Can Be Controllably Activated by Red Light

“…Controllable activation of prodrugs at the tumor site has been widely explored in cancer chemotherapy, aiming to increase the therapeutic window of conventional chemotherapeutics with limited tumor-targeting property. 1,2 Both endogenous activators within tumor microenvironments including overexpressed tumor-associated enzymes, 3 elevated levels of reactive oxygen species (ROS), 4 hypoxia 5 and low pH, 6 and exogenous activators including catalysts, 7 light, 8 and ultrasound 9 have been utilized to activate prodrugs. Among them, photoactivation is particularly attractive because it can enable the activation of prodrugs in a high spatial and temporal manner.…”

Piezoelectric Materials as Sonodynamic Sensitizers to Safely Ablate Tumors: A Case Study Using Black Phosphorus

“…We next set to examine whether our BP nanosheet under ultrasound exposure produces ROS and, if so, whether the produced ROS species is •OH as predicted by our analysis above. Using dichlorofluorescein (DCFH) as a fluorescent probe to detect ROS, 45 we find that under ultrasound (53 kHz) excitation, the BP nanosheet dispersion produces a significant amount of ROS (Figure 3a), as indicated by the dramatic increase in fluorescence intensity at ∼525 nm (Figure S8a). It should be noted the aqueous BP nanosheet dispersion naturally produces a detectable amount of ROS, likely due to transfer of electron and holes randomly generated because of thermal effects; 46 however, ultrasound exposure makes BP nanosheet produce 6.5 times more ROS (Figure 3a).…”

Photodynamic Therapy Directed by Three‐Photon Active Rigid Plane Organic Photosensitizer

“…Another commonly applied indicator for detecting ROS, 2′,7′‐Dichlorodihydrofluorescein diacetate (DCFH‐DA) [ 20,21 ] was also used to evaluate ROS production rate. It is also demonstrated in Figure 2c, [ 21 ] Figure S16 (Supporting Information) that under laser irradiation, the fluorescence intensity of DCFH‐DA was continuously raised likely due to the oxidation of DCFH to DCF. Noteworthy that under hypoxia circumstance U‐TsO also revealed considerable ROS conversion efficiency, offering potential utilization in hypoxia tumor conditions.…”