PMID- 30339360 OWN - NLM STAT- MEDLINE DCOM- 20190215 LR - 20200225 IS - 1944-8252 (Electronic) IS - 1944-8244 (Print) IS - 1944-8244 (Linking) VI - 10 IP - 43 DP - 2018 Oct 31 TI - Nanoparticle-Mediated Acoustic Cavitation Enables High Intensity Focused Ultrasound Ablation Without Tissue Heating. PG - 36786-36795 LID - 10.1021/acsami.8b15368 [doi] AB - While thermal ablation of various solid tumors has been demonstrated using high intensity focused ultrasound (HIFU), the therapeutic outcomes of this technique are still unsatisfactory because of common recurrence of thermally ablated cancers and treatment side effects due to the high ultrasound intensity and acoustic pressure requirements. More precise ablation of tumors can be achieved by generating cavitating bubbles in the tissue using shorter pulses with higher acoustic pressures, which induce mechanical damage rather than thermal. However, it has remained as a challenge to safely deliver the acoustic pressures required for mechanical ablation of solid tumors. Here, we report a method to achieve mechanical ablation at lower acoustic pressures by utilizing phospholipid-stabilized hydrophobic mesoporous silica nanoparticles (PL-hMSN). The PL-hMSNs act as seeds for nucleation of cavitation events and thus significantly reduce the peak negative pressures and spatial-average temporal-average HIFU intensities needed to achieve mechanical ablation. Substantial mechanical damage was observed in the red blood cell or tumor spheroid containing tissue mimicking phantoms at PL-hMSN concentrations as low as 10 mug mL(-1), after only 5 s of HIFU treatment with peak negative pressures approximately 11 MPa and duty cycles approximately 0.01%. Even the application of HIFU (peak negative pressure of 16.8 MPa and duty cycle of 0.017%) for 1 min in the presence of PL-hMSN (200 mug mL(-1)) did not cause any detectable temperature increase in tissue-mimicking phantoms. In addition, the mechanical effects of cavitation promoted by PL-hMSNs were observed up to 0.5 mm from the center of the cavitation events. This method may thus also improve delivery of therapeutics or nanoparticles to tumor environments with limited macromolecular transport. FAU - Yildirim, Adem AU - Yildirim A AD - Department of Chemical and Biological Engineering , University of Colorado Boulder , Boulder , Colorado 80303 , United States. FAU - Shi, Dennis AU - Shi D AD - Department of Chemical and Biological Engineering , University of Colorado Boulder , Boulder , Colorado 80303 , United States. FAU - Roy, Shambojit AU - Roy S AD - Department of Chemical and Biological Engineering , University of Colorado Boulder , Boulder , Colorado 80303 , United States. FAU - Blum, Nicholas T AU - Blum NT AD - Department of Chemical and Biological Engineering , University of Colorado Boulder , Boulder , Colorado 80303 , United States. FAU - Chattaraj, Rajarshi AU - Chattaraj R AD - Department of Mechanical Engineering , University of Colorado Boulder , Boulder , Colorado 80309 , United States. FAU - Cha, Jennifer N AU - Cha JN AUID- ORCID: 0000-0002-2840-1653 AD - Department of Chemical and Biological Engineering , University of Colorado Boulder , Boulder , Colorado 80303 , United States. FAU - Goodwin, Andrew P AU - Goodwin AP AUID- ORCID: 0000-0002-7284-4005 AD - Department of Chemical and Biological Engineering , University of Colorado Boulder , Boulder , Colorado 80303 , United States. LA - eng GR - DP2 EB020401/EB/NIBIB NIH HHS/United States GR - R03 EB021432/EB/NIBIB NIH HHS/United States PT - Journal Article DEP - 20181019 PL - United States TA - ACS Appl Mater Interfaces JT - ACS applied materials & interfaces JID - 101504991 RN - 0 (Contrast Media) RN - 7631-86-9 (Silicon Dioxide) SB - IM MH - *Acoustics MH - Animals MH - Cattle MH - Cell Line, Tumor MH - Contrast Media/chemistry MH - Erythrocytes/metabolism MH - Hot Temperature MH - Humans MH - Mice MH - Nanoparticles/*chemistry MH - Neoplasms/*therapy MH - Phantoms, Imaging MH - Pressure MH - Silicon Dioxide/chemistry MH - Ultrasonic Therapy/*methods PMC - PMC6702128 MID - NIHMS1044303 OTO - NOTNLM OT - cancer therapy OT - cavitation OT - high intensity focused ultrasound OT - mesoporous silica nanoparticles OT - tumor ablation EDAT- 2018/10/20 06:00 MHDA- 2019/02/16 06:00 PMCR- 2019/10/31 CRDT- 2018/10/20 06:00 PHST- 2018/10/20 06:00 [pubmed] PHST- 2019/02/16 06:00 [medline] PHST- 2018/10/20 06:00 [entrez] PHST- 2019/10/31 00:00 [pmc-release] AID - 10.1021/acsami.8b15368 [doi] PST - ppublish SO - ACS Appl Mater Interfaces. 2018 Oct 31;10(43):36786-36795. doi: 10.1021/acsami.8b15368. Epub 2018 Oct 19.