Nanomedicine and Targeted Therapy Laboratory
The laboratory of Nanomedicine and Targeted Therapy specializes in the synthesis of imageable and stimuli sensitive nanocarriers for device (HIFU/proton) directed chemo-immunotherapy of cancerous tissue. We are also devising novel cell- and bacteria-based technologies for enhancing circulatory half-life of nanoparticles, and hypoxic cell targeting. Established on the concept of bench-to-bedside research, our goal is to bridge the gap between preclinical and clinical research, and ease clinical translation of nanopharmaceutics.
Research in the NTTL focuses on chemo-immunotherapy of solid-tumors with nanomedicines and focused ultrasound.
Improving local and abscopal solid-tumor immunotherapy
Depending on the tumor microenvironment and cancer types, <50% of patients with advanced-stage disease respond to currently available immunotherapeutics. To improve sensitivity to immunotherapies, our lab is leveraging focused ultrasound and nanomedicines-based immunoadjuvants to reprogram solid tumors locally, and thereby improve therapeutic response against treated and untreated tumors (abscopal effect). Specifically, our lab has developed a biocompatible calreticulin-liposome nanoparticle that upon direct intratumoral injection enhances immune-mediated detection of solid tumors in the presence of ultrasound exposures. Related works in the laboratory are focusing on re-purposing systemic toxic agents (e.g. tumoricidal bacteria, anti-CD40 agonists, etc.) with focused ultrasound for immunotherapy applications.
Translating device-directed nanomedicines to canine immunotherapy trials
Many types of canine cancers are very similar in behavior to aggressive human cancers originating in various parts of bodies. We are translating our in-house developed nanomedicines and focused ultrasound therapy for treating canine cancer patients. Built on the premise of promoting one-health and one-medicine, we have been able to establish a state-of-the-art bench-to-clinic that is actively performing several veterinary cancer trials in patients. Human oncology researchers are also collaborating with us to promote parallel trials utilizing these concepts in veterinary and human settings.
Chemo-immunotherapy therapy with localized solid-tumor heating
Our laboratory has conducted several pioneering studies demonstrating the improved benefits of focused ultrasound directed solid-tumor chemotherapy. Ongoing work in the laboratory are focusing on how FUS-induced local heating and stress can be utilized to modify the tumor microenvironment, upregulate pro-phagocytic signals and overall tumor immunity with chemotherapy agents.
Funding and Infrastructure
Funding (Past and Ongoing)
- College of Veterinary Medicine
- Defense Threat Reduction Agency
- Focused Ultrasound Foundation
- National Cancer Institute
- National Institutes of Health
- NIH Oklahoma Center for Respiratory and Infectious Diseases
- Oklahoma Center for the Advancement of Science & Technology
- Oklahoma Center for Adult Stem Cell Research
- Petco Foundation
- Technology Bussiness Development Program, Oklahoma State University
Infrastructure and Resources
- Three Labconco biological safety cabinets and two CO2 incubators for routine cell cultures
- Sorvall Legend X1R (refrigerated) centrifuge
- Olympus inverted microscope for tissue culture
- Lipex Extruder
- -20°C and -86° freezers
- Mettler electrical balance
- BioSpec Tissue Homozeniser
- Branson Bath Sonicator
- Heidolph Collegiate RotaVap
- Mini centrifuge
- Liquid N2 storage dewars, and N2 transport dewars
- pH meter and water bath
- Olympus IX81 Automated Inverted Epi-Fluorescence Microscope (equipped with Zero Drift Controller, Motorized XY Stage, Phase Contrast, XM10IR Monochrome Digital Camera with Extended Near-IR Response, 10x, 20x, 40x, and oil-emersion 63x fluorescent objectives), and Metamorph imaging analysis software.
- VIFU Dry Type System- ( One imaging system: Ecube 9 with 2 ultrasound transducers
- (S4-12 and L3-12H), One VIFU- HIFU module, Dry HIFU transducer assembly (Standard 1.0MHz) and table
- Vortex Mixer
- Hot plate/stirrer
- Vacuum dessicators
- Olympus DSU Spinning Disk inverted confocal microscope ( equipped with Automated Scan-Slide Option for Metamorph)
- Alpinion Wet Type HIFU system, (1.50 MHz, H-186) with animal holder mount fixtures: small holder (rodents) - Fixtures: large holder (Rat), with the state-of-the-art software guidance
- UV-Visible/Fluorescence spectrometer with plate reader
- ZetaPALS instrument for nanoparticle zeta-potential/size measurement
- Cary Eclipse fluorometer
- Xtreme II invivo imaging system