The work aimed at developing a novel MRI-based theranostic protocol for improving the anticancer efficacy of a Doxil-like liposomal formulation. The goal was achieved stimulating the intratumor release of the drug from the nanocarrier and favoring its diffusion in the lesion by the sequential application of low-intensity pulsed ultrasound. The protocol was tested on mice bearing a syngeneic breast cancer model. The combination of acoustic waves with different characteristics allowed for: i) the release of the drug and the co-encapsulated MRI agent (Gadoteridol) from the liposomes in the vessels of the tumor region, and ii) the extravasation of the released material, as well as intact liposomes, in the tumor stroma. The MR-T1 contrast enhancement measured in the tumor reported on the delivery and US-triggered release of Doxorubicin. The developed protocol resulted in a marked increase in the intratumor drug concentration that, in turn, led to the complete regression of the lesion. The protocol has a good clinical translatability because all the components of the theranostic agent (Doxorubicin, liposomes, Gadoteridol) are approved for human use. MRIJbased% procedure% for% the% in$ vivo% visualization% of% the% release% of% an% anticancer% drug% (Doxorubicin)% from% liposomes% stimulated% by% the% local% application% of% pulsed% lowJintensity% planar% ultrasound.% First,% we% investigated% the% in% vitro% release% properties% of% several% nanovesicular% carriers% under% US% application% and% demonstrated% that% the% release% was% i)% caused% by% the% mechanical% characteristics% of% the% US% stimulus,% ii)% very% sensitive% to% the% composition% of% the% particle% membrane,% and% iii)% MRI% detectable% (Giustetto% et$ al.,% J.$ Med.$ Imaging$Health$Inf.%3,%356J366%(2013)).%Next,%the%MRI%potential%of%the%method%was%demonstrated%in$vivo%on%a% mouse%model%of%melanoma% (Rizzitelli%et$al.,%Nanomedicine%10,%901J904%(2014)).%More%recently,%the%theranostic% protocol% was% implemented% by% the% encapsulation% of% Doxorubicin,% and% both% the% MRI% performance% and% the% therapeutic% benefits% associated% with% the% USJtriggered% intratumor% release% of% the% drug% on% a% mouse% model% of% breast%cancer%were%reported%(Rizzitelli%et$al.,%J.$Control.$Release%202,%21J30% (2015)).% In%the%submitted%paper,%we%further%improved%the%performance%of%the%method%through%the%sequential% application%of%two%different%low%intensity%US%stimuli,%one%inducing%a%permeabilization%of%the%tumor%vascular% endothelium,%and%the%other%stimulating%the%release%of%the%drug%from%the%nanocarrier.%The%synergy%between% the%two%short%stimuli%(only%3%minutes%in%total)%allowed%for%a%complete%tumor%regression%in%a%mouse%model%of% breast%cancer.%Furthermore,%also%the%MRI%detectability%of%the%process%was%improved.%% Though% several% examples% dealing% with% the% use% of% US% (but% mostly% focused% with% highJintensity)% for% triggering% drug% release% can% be% found% in% literature,% this% is,% to% our% knowledge,% the% case% with% the% highest% therap...