A method of distributing microparticles is provided, the method comprising: providing a plurality of microparticles at an insertion site in a medium; applying ultrasound to the insertion site that generates gas bubbles by cavitation at cavitation nuclei located at the insertion site and drives movement of the gas bubbles such that the gas bubbles drive movement of the microparticles into a desired spatial distribution in the tumour. The method may be a method of treating a tumour, and the microparticles may comprise a radioisotope for treating the tumour. Microparticles for use in the treatment of a tumour by the method are also disclosed.

Provided herein are methods of treating brain cancer in a subject, comprising evaluating one or more biological samples from a subject who has brain cancer for the presence of a miRNAs and administering interleukin-12 (IL-12); an immunogenic composition of human telomerase reverse transcriptase (hTERT), Wilms Tumor-1 (WT-1), and prostate specific membrane antigen (PSMA); and an anti-programmed cell death receptor 1 (PD-1) antibody to said subject if the subject has an increased expression level of the mIR-331-3p miRNA or isomiRs thereof and the miR-1537-3p miRNA or isomiRs thereof relative to a control population of subjects. Also provided herein are methods of treating brain cancer in a subject, comprising measuring an expression level of at least one mRNA biomarker selected from SYNGR3, OTX1, GABBR2, LHX1, CADM3, MLLT11, MNX1, GRB14, SLC34A2, PHYHIP, WNT10B, SLC17A6, CRLF1, HOXD13, TGFβR3, UBA7, SFRP4, or any combination thereof, in a tumor sample from a subject and administering IL-12; an immunogenic composition hTERT, WT-1, and PSMA; and an anti-PD-1 antibody to said subject if the expression level of SYNGR3, OTX1, GABBR2, LHX1, CADM3, MLLT11, MNX1, GRB14, SLC34A2, PHYHIP, WNT10B, SLC17A6, CRLF1 and HOXD13 is decreased or if the expression level of TGFβR3, UBA7, SFRP4 is increased.

This invention provides methods and systems for achieving high-specificity killing of targeted cells using Magneto-Electric Nano-Particles (MENPs) and functional or diagnostic imaging that detects changes at the cellular level. Embodiments comprise injecting into a patient's body manufactured MENPs that have a higher tendency to accumulate near or attach to targeted cells through one or more physical forces and/or biological mechanisms; and applying a magnetic field to the MENPs to generate an action that is sufficient to cause death of the targeted cells, and using an imaging apparatus to image or detect a specific property of the MENPs or changes in a property of the MENPs due to the coupling of the MENPs with their surrounding environment.

The present invention relates to a method for increasing the blood-brain barrier permeability, and more particularly, to a method for increasing the blood-brain barrier permeability, the method including: (S1) a step of delivering a nanogenerator carrying a nitric oxide (NO) donor to a site adjacent to the blood-brain barrier; (S2) a step of delivering a first triggering stimulus to an area where the nanogenerator has been delivered so as to release nitric oxide from the nanogenerator; and (S3) a step of allowing the released nitric oxide to activate matrix metallopeptidase-9 (MMP-9) and inducing the activated MMP-9 to weaken the tight junction between a cerebrovascular endothelial cell and another cerebrovascular endothelial cell.

Described herein are high-boiling-point-based nanoparticles that release drugs specifically at the focus of ultrasound. The specific conjunction of the high-boiling-point-based nanoparticle formulation with low-frequency ultrasound can be used to deliver therapeutics in a safe and effective manner. The effectiveness and safety of the release is validated in vitro and in non-human primates.

The present invention generally relates to composition matters and methods useful for gene delivery and an option for therapeutic treatment of various diseases. Particularly, this disclosure relates to a plasmid vector comprising a fusion of a plurality of genes comprising a gene of a chemokine or a cytokine, a gene for a targeting polypeptide and genes for one or more polypeptide linkers. Methods of use and composition matters are within the scope of this disclosure.

The present invention relates to an ultrasound contrast agent for use in treating a retina disorder by transiently disrupting the blood-retinal barrier (BRB) of a human, wherein the ultrasound contrast agent is administered just before and/or during the application, to the retina of the human, of an unfocused ultrasound (US) beam. The present invention further relates to a therapeutically active agent for use in treating a retina disorder in a human, wherein the therapeutically active agent is to be delivered in combination with an ultrasound contrast agent, which is administered before and/or during the application, to the retina of the human, of an unfocused ultrasound (US) beam in order to transiently disrupting the blood-retinal barrier (BRB) of the human, to allow the therapeutically active agent to cross the BRB and to target the retina. The present invention also relates to an eye ultrasound delivery device that may be used to treat a retina disorder.

Proposed are an ultrasound-assisted drug delivery carrier containing a ligand linked with a drug through an ester bond, a phospholipid, and a PEGylated phospholipid, a composition for drug delivery including the drug delivery carrier, and a method of preventing or treating a disease including administering the composition to an individual other than a human and releasing a drug by subjecting the site of administration of the composition to ultrasound irradiation. The ultrasound-assisted drug delivery carrier containing a ligand linked with a drug through an ester bond, a phospholipid, and a PEGylated phospholipid can be provided in the form of microbubbles or nanobubbles, and is capable of accelerating drug release due to collapse of the bubbles and promotion of hydrolysis of the ester bond during ultrasound irradiation, making it possible to deliver the drug to a desired site with high efficiency.

System for inducing sonoporation of a drug into cancer cells in a tumor and method thereof, the system comprising a generator configured to provide electrical energy at an ultrasound frequency; an ultrasound probe electrically connected to the generator and configured to convert the electrical energy into low intensity pulsed ultrasonic waves defined by operation parameters, said operation parameters comprising the frequency, the duty cycle, the operation time of the ultrasonic waves; an input device enabling an operator to enter configuration data comprising: type of tumor, type of drug, localization of secondary tumor, anthropometric measurements and grade of tumor, and a processor configured to determine the values of the operation parameters on the basis of the entered configuration data and control the generator and the ultrasound probe to operate according to said determined values, wherein the value of the frequency is determined on the basis of the type of tumor, the localization of the tumor, the grade of tumor and the anthropometric measurements, the value of the duty cycle is determined on the basis of the drug, the type of tumor and the grade of the tumor, and the value of said operation time being determined on the basis of at least the type of tumor and the type of drug.

Systems and methods for temporarily altering a tissue characteristic at a target region, such as the blood-brain barrier, include causing an ultrasound transducer to transmit acoustic energy to the target region at a transmission frequency; acquiring a cumulative harmonic response from at least the target region; and operating the transducer based at least in part on the acquired cumulative harmonic response.