Low frequency nanobubble-enhanced ultrasound mechanotherapy for noninvasive cancer surgery

Abstract

Taking microbubbles contrast agents into the nanoscale holds the promise for noninvasive cancer therapy. However, the nanobubbles small size limits the obtained bioeffects as a result of ultrasound cavitation, when...

Nanobubble-mediated cancer cell sonoporation using low-frequency ultrasound

“…In a recent publication we showed that low frequency insonation of tumors without NBs at these settings did not cause mechanical damage to the tumor and that our treatment combining low frequency US and NBs did not impact other internal organs. 19 The optimal uptake was observed between 300 kPa and 500 kPa, and no significant difference was found between these pressures for all the tested FITC sizes. Increasing the PNP to 800 kPa led to decreased uptake for all FITC molecules tested (Fig.…”

“…[52][53][54][55] Based on the Blake threshold effect, the use of low frequency US was found to generate large NBs oscillation permitting NBsmediated therapeutic applications despite their reduced size. 19,29 Here, we described an enhanced sonoporation platform using NBs with a mean diameter of 170 nm that can be systemically injected. This overcomes current sonoporation limitations that stem from the large MB diameter used in most sonoporation studies.…”

“…However, we can say that in a previous work that focused on mechanical fractionation of tumors using NBs, we were able to achieve significant bioeffects with a systemic injection of NBs (ref. 19). Therefore, we can anticipate that a sufficient amount of NBs can reach the tumor for sonopora-tion.…”

“…2,15,16 The development of nanobubbles (NBs) has expanded gasbubble effects beyond the vascular compartment because of their small size (less than 500 nm) that enables effective tumor uptake via the leaky tumor vasculature. [17][18][19] In sonoporation studies, NBs have been employed for the delivery of drugs and genes at high frequencies. 20,21 However, the effective delivery of large molecules requires sufficiently high-amplitude NBs oscillations to apply enough mechanical force to generate large pores in adjacent cell membranes.…”

Efficacy optimization of low frequency microbubble-mediated sonoporation as a drug delivery platform to cancer cells

“…Low frequency US was used to treat over 500 patients for brain indications applications. Our lab uniquely uses the high amplitude MB oscillations that occur at this low frequency to develop mechanically-induced bioeffects at low PNPs, such as low energy bubble-mediated histotripsy ( Bismuth et al, 2021 ; Bismuth et al, 2022 ). Here, we showed that coupled with low frequency excitation, MBs can be used as mechanical therapeutic warheads that generate sufficiently large pores in cancer cell membranes to deliver large molecules.…”