University of Pittsburgh

Jianjun Wang

Flordeliza Villanueva

Xucai Chen

Charles F McTiernan

Andrew Carson

William Richard Wagner

Andrew Fisher

John J Pacella

Catalin Toma

Joon S Lee

The invention pertains to a lipid-based microbubble stably binding a plurality of nucleic acids, and a method of delivering the microbubble and nucleic acids to a specific target site using ultrasound. The delivered nucleic acids create transgenic cells (i.e., for example, a transgenic tumor cell), wherein the transgenic cell expresses the proteins encoded by the delivered nucleic acids. This technology provides a significant improvement for microbubble-drug delivery platforms as known microbubble do not efficiently bind nucleic acids. The improvements described herein include but are not limited to identifying proper lipid proportionality ratios and/or cationic surfactant layers that provide an optimum mechanical index compatible with ultrasonics. Microbubble perfusion and/or nucleic acid delivery may be performed by a combination of imaging and ultrasound/microbubble targeted delivery to simultaneously perform low power two-dimensional imaging and high power microbubble destruction. Such systems are useful in therapeutics and/or diagnostics. For example, the data disclosed herein shows proof of principle in conjunction with the delivery of therapeutic siRNA molecules to slow tumor growth.

Microbubble nucleic acid delivery platform

The invention pertains to a lipid-based microbubble stably binding a plurality of nucleic acids, and a method of delivering the microbubble and nucleic acids to a specific target site using ultrasound. The delivered nucleic acids create transgenic cells (i.e., for example, a transgenic tumor cell), wherein the transgenic cell expresses the proteins encoded by the delivered nucleic acids. This technology provides a significant improvement for microbubble-drug delivery platforms as known microbubble do not efficiently bind nucleic acids. The improvements described herein include but are not limited to identifying proper lipid proportionality ratios and/or cationic surfactant layers that provide an optimum mechanical index compatible with ultrasonics. Microbubble perfusion and/or nucleic acid delivery may be performed by a combination of imaging and ultrasound/microbubble targeted delivery to simultaneously perform low power two-dimensional imaging and high power microbubble destruction. Such systems are useful in therapeutics and/or diagnositics. For example, the data disclosed herein shows proof of principle in conjunction with the delivery of therapeutic siRNA molecules to slow tumor growth.

Methods for creating a transgenic cell with microbubbles

Various methods of performing ultrasound contrast assisted therapy are provided. One such method includes delivering a plurality of microbubble-based ultrasound contrast agents to a target area and disrupting the microbubble-based ultrasound contrast agents by delivering tone bursts of ultrasound to the target area. The oscillation of the microbubble-based ultrasound contrast agents can be achieved by delivering ultrasound tone bursts of greater than 5 acoustic cycles with a pulse repetition frequency of between 0.01 and 20 Hz, with pressure greater than 0.3 MPa.

Methods and devices for ultrasound contrast-assisted therapy

Custom designed microbubble contrast agents and techniques of ultrasound delivery optimized for gene therapy

This invention addresses the clinical problem of how to optimize biological cell based therapies, such as stem cell therapy. Currently, cell therapies administered by intravenous, intra-arterial, and/or direct tissue injection are limited by the lack of clinically available imaging methods to detect the in vivo fate of the administered cells. There are many efforts underway to develop imaging strategies for stem cells in vivo, including radionuclide and MRI-based approaches. However, these approaches are limited by potential safety issues (e.g. radioactive exposure of stem cells, toxicity of iron particles used for MRI) and difficulty in serial tracking due to complex instrumentation and/or the requirement for repetitive radiation exposure.

Intracellular microbubble for imaging an anatomical site

The disclosed technology describes compositions and methods useful for providing cell based therapy. For example, one embodiment of cell based therapy involves the regeneration of injured tissue and/or promoting wound healing. Certain embodiments provide improved therapeutic compositions using microbubbles by delivering biological progenitor cells to the injured tissues. The administration of the microbubbles is directed by acoustic radiation forces that interact with embodiments of microbubbles comprising an acoustically active gas. As such, a high efficiency of progenitor cell delivery to injured tissue is realized. One advantage of this technique over targeted delivery of pharmaceutical compounds, is that the delivered progenitors cells may be derived from the patient (i.e., personalized therapy), thereby avoiding side effects, allergic reactions, and overall problems associated with refractive drug responses.

Growing community of inventors

Pittsburgh, PA, United States of America

Jianjun Wang