Research in our lab is focused on the development of nanomedicine for diagnosis and combinatorial treatment of cancer and other diseases. Particularly, we are developing theranostic nano-agents for application in chemotherapy, hyperthermia, gene therapy, phototherapy, fluorescence and photoacoustic detection for treatment of diseases.
Combining the capability of real-time imaging and therapy into a single agent has high translational potential for disease treatment, including cancer. Presently, our lab is focused on the development of photo-theranostic nanoscale agents for use in optical/photoacoustic imaging, image-guided phototherapy, image-guided surgery and intraoperative therapy. Near-infrared (NIR) light is not significantly absorbed by bodily tissue and fluid allowing for uninterrupted NIR light to penetrate further within the body. This capability is paired with the dye-loaded nanoparticles that absorb specifically in the NIR region to generate fluorescence, photoacoustic signal or/and heat under NIR light. The main goal is to develop nano-agents for assistance in the accurate location/ diagnosis of diseased tissue, with subsequent immediate treatment.
Magnetic Hyperthermia: Combinatorial Treatments
Hyperthermia therapy for cancer treatment is a very promising approach. However, the issue with hyperthermia is the difficulty in heating only the local tumor area to the required temperature without harming surrounding healthy tissue. Despite its promising therapeutic potential, nanoparticle-mediated magnetic hyperthermia is currently limited to treatment of localized and relatively accessible cancer tumors because the required therapeutic temperatures above 40 °C can only be achieved by direct intratumoral injection of conventional iron oxide nanoparticles. Our goal is to develop efficient nanoparticles with high heating capacity that can efficiently accumulate at tumor sites following systemic administration and generate desirable intratumoral temperatures upon exposure to an alternating magnetic field (AMF). We are also evaluating hyperthermia treatment efficacy in combination with chemotherapy, gene therapy and phototherapy.
Muscle wasting is a debilitating syndrome that occurs in numerous disease states and is an especially common consequence of cancer. We have focused our efforts on the development of a safe therapy that combats muscle wasting in cancer patients without the need for special dietary and exercise requirements. Currently, we are developing an effective nanoplatform for messenger RNA (the genetic blueprint that cells use to manufacture numerous proteins) delivery, with the aim to increase a protein inside the body that is responsible for muscular growth. Results of the ongoing pilot study reveal that overexpressed follistatin is also capable of modulating tumor cell activity, particularly regarding proliferation and migration. We show that, in addition to inducing muscle preservation via myostatin inhibition, follistatin also suppresses tumor cell activity by binding activin A, which was previously shown to be a driver of both tumor proliferation and cancer cachexia. The developed polymeric delivery platform could be an efficient therapeutic option for the safe and efficacious treatment of muscle wasting in cancer patients and could potentially inhibit cancer progression.
Schumann C, Nguyen DX, Norgard M, Bortnyak Y, Korzun T, Chan S, Lorenz AS, Moses AS, Albarqi HA, Wong L, Michaelis K, Zhu X, Alani AWG, Taratula OR, Krasnow S, Marks DL, Taratula O. Increasing lean muscle mass in mice via nanoparticle-mediated hepatic delivery of follistatin mRNA. Theranostics 2018; 8(19):5276-5288. doi:10.7150/thno.27847. Available fromhttp://www.thno.org/v08p5276.htm
siRNA Gene Delivery for the Treatment of Metastatic Ovarian Cancer
The high mortality of ovarian cancer stems from its unique metastatic behavior not shared with other cancers. DJ-1 is a multifunctional protein that has recently been implicated as a key oncogenic driver and biomarker for various cancers, including ovarian cancer. It was also documented that increased DJ-1 expression positively correlates with lower survival in ovarian cancer patients. We have recently discovered that DJ-1 suppression in combination with a low dose of chemo-therapeutic drug provides a superior therapeutic response as compared to each therapy alone.