Early detection of cancer substantially increases the probability of its successful and effective treatment. Theranostics is an emerging field in medical research that can potentially improve overall patient therapy andoutcome by combining diagnostic and specific therapeutic properties. Although nanoparticles allow for distinctadvantages in the field of therapy of different diseases, a combination of both diagnostic and therapeuticmodalities in a single nanoparticle may be associated with certain difficulties. Therefore, it may be ideal todevelop a separated, but integrated multi-particle system for theranostics. The efficacy of the cancer detectionby magnetic resonance imaging (MRI) and chemotherapy of primary tumors and metastases can besignificantly improved by targeting of nanoparticles containing a contrast agent or anticancer drug specificallyto cancer cells. Consequently, the overall goal of the planned investigations consists of the development,characterization, and preclinical in vivo testing of multi-particle cancer-targeted system for diagnostics by MRIand chemotherapy of primary tumors and metastases. In the present theranostic study, manganese oxidenanoparticles (Mn3O4) will be used as MRI contrast agents; poor water-soluble anticancer drug paclitaxel(PTX) – as an anticancer drug; neutral liposomes – as carriers for PTX; a modified luteinizing hormonereleasing hormone (LHRH) peptide – as targeting moiety. The developed multi-particle theranostic system willbe tested in vitro and in vivo using murine models of human ovarian and lung cancers. However, the proposedapproach may be extended for other types of carriers/particles, contrast agents, and anticancer drugs as wellas other types of cancer. The specific aims of the proposal are: (1) To synthesize and characterize cancer-targeted nanoparticles for imaging and treatment of cancers; (2) To evaluate the efficacy of the synthesizednanoparticles as MRI contrast agents for the detection of primary tumors and metastases in vivo using murinemodels of lung and ovarian cancers; (3) To evaluate the effect of formulation and drug delivery route on wholebody tissue disposition and pharmacokinetics of paclitaxel and (4) To examine in vivo antitumor efficacy andadverse side effects of combined imaging and chemotherapy with PEGylated cancer-targeted liposomescontaining PTX using orthotopic murine model of lung cancer after intravenous and inhalation delivery. It isexpected that proposed approach and the use of the developed cancer-targeted nanoparticle-based MRIcontrast agents and chemotherapeutic drug will substantially enhance the efficacy of the detection of primarytumors and metastases and therapy for cancers, while limiting adverse side effects of the treatments. Theplanned studies have the potential to significantly impact the field of imaging and drug delivery and to improvethe efficiency of therapy of lung and other types of cancer.
|Effective start/end date||4/21/17 → 3/31/22|
- National Institutes of Health (NIH)