Combining doxorubicin-nanobubbles and shockwaves for anaplastic thyroid cancer treatment: preclinical study in a xenograft mouse model

Abstract

Anaplastic thyroid cancer is one of the most lethal diseases, and a curative therapy does not exist. Doxorubicin, the only drug approved for anaplastic thyroid cancer treatment, has a very low response rate and causes numerous side effects among which cardiotoxicity is the most prominent. Thus, doxorubicin delivery to the tumor site could be an import goal aimed to improve the drug efficacy and to reduce its systemic side effects. We recently reported that, in human anaplastic thyroid cancer cell lines, combining doxorubicin-loaded nanobubbles with extracorporeal shock waves, acoustic waves used in lithotripsy and orthopedics without side effects, increased the intracellular drug content and cytotoxicity. In the present study, we tested the efficacy of this treatment on a human anaplastic thyroid cancer xenograft mouse model. After 21 days, the combined treatment determined the greatest drug accumulation in tumors with consequent reduction of tumor volume and weight, and an extension of the tumor doubling time. Mechanistically, the treatment induced tumor apoptosis and decreased cell proliferation. Finally, although doxorubicin caused the increase of fibrosis markers and oxidative stress in animal hearts, loading doxorubicin into nanobubbles avoided these effects preventing heart damage. The improvement of doxorubicin anti-tumor effects together with the prevention of heart damage suggests that the combination of doxorubicin-loaded nanobubbles with extracorporeal shock waves might be a promising drug delivery system for anaplastic thyroid cancer treatment.

Glutathione/pH-responsive nanosponges enhance strigolactone delivery to prostate cancer cells

“…It is worth noting that the use of a drug within a nanodelivery system presents significant advantages versus normal cells. One of them concerns the capability to enhance the pharmacokinetics and biodistribution profiles, thereby improving drug efficacy and reducing side effects [ 40 , 41 ]. GSH/pH-NS might modify the biodistribution and intracellular release kinetics of the incorporated SLs.…”

Improved Healing of Diabetic Foot Ulcer upon Oxygenation Therapeutics through Oxygen-Loading Nanoperfluorocarbon Triggered by Radial Extracorporeal Shock Wave

“…Additionally, oxypherol (Fluosol-43), a type of PFC, has obtained US Food and Drug Administration (FDA) approval for improving myocardial oxygenation and preventing abnormalities in ventricular function [25]. Thus, Nano-PFC can be used as an NDDS to deliver molecules, such as drugs and oxygen, to target tissues and release the contents in response to physical stimuli [20,23,26].…”

Radial extracorporeal shock wave promotes the enhanced permeability and retention effect to reinforce cancer nanothermotherapeutics

“…have combined ESW with nanomedicine as anticancer therapy thus far. Only a few studies employed ESW as a trigger for drug release [52,53] or sonodynamic therapy [54,55], whereas no studies have assessed the potential influence of rESWT on the EPR effect. In the current study, we uncovered the combinatory therapeutics between rESWT and nanothermotherapeutics in elevating the tumor-killing efficacy through enhanced EPR effect.…”