Abstract: In a method for enhancing localized delivery of a diagnostic or therapeutic agent using focused ultrasound (FUS), ultrasound-controllable drug carriers are administered into a blood vessel. Each drug carrier comprises an ultrasound-sensitive microbubble loaded with the diagnostic or therapeutic agent. The drug carriers are aggregated inside the vessel both along a radial direction and a longitudinal direction by application of an aggregation FUS sequence. Subsequently the diagnostic or therapeutic agent is released from the drug carriers by application of an uncaging FUS sequence. The aggregation and uncaging sequences are applied using FUS below a threshold power level such that harmful cavitation is avoided, as evidenced by the absence of broadband emissions and preferably non-integer harmonics from an emission spectrum of the drug carriers. Thereby damage to the vasculature by the FUS sequence is avoided.

Abstract: Use of size-isolated microbubbles (SIMs) for sonoporation using a sonoporation system. The sonoporation system may include a SIM product administered in conjunction with an administered drug. Targeted ultrasound energy using an ultrasound device of the sonoporation system may result in sonoporation in response to cavitation of the SIM product in a targeted area of soft tissue. In turn, targeted delivery of the drug to the targeted area may occur. Results demonstrate improved outcomes using much reduced drug doses that allow for side effects and adverse reactions to be reduced or eliminated when used in conjunction with sonoporation as contemplated herein.

Abstract: The blood-brain barrier (BBB) excludes most drugs and poses a significant challenge to treat brain diseases. Current methods for BBB opening yield modest outcomes in clinical applications due to safety and toxicity. This disclosure relates to methods of optically opening the BBB by laser excitation of tight-junction targeted nanoparticles to induce BBB transient opening. The excitation of plasmonic nanoparticles produces localized effects such as nanoscale heating and photomechanical force leading to BBB transiently opening to allow macromolecules across it. The safe and predictable platform for brain drug delivery will improve therapies for brain disease such as cancers, infections and neurologic disorders.