Photoacoustic imaging of endometriosis with nanoparticle contrast agents

PROJECT SUMMARY Endometriosis is an incurable disease in which endometrial tissue grows outside the uterus, causing affected women to endure pain during periods and/or sexual intercourse and suffer from reduced fertility and diminished quality of life. Current treatments include anti-inflammatory drugs, hormonal therapies, and surgery (performed alone or in combination with ablation to destroy the lining of the uterus), but none of these are adequate so recurrence rates among patients are extremely high. Earlier diagnosis and/or improved resection of lesions enabled by advanced imaging technologies may overcome the challenges associated with endometriosis patient care. To address the critical need for better endometriosis visualization, we will develop inflammation- targeted, light-responsive nanoparticles that can accumulate in endometriosis lesions (which are characterized by high levels of inflammation) and serve as photoacoustic imaging contrast agents to visualize lesions with enhanced sensitivity. This technology could be transformative as there are currently no reliable blood tests or imaging techniques to accurately diagnose endometriosis, and improving image-guided resection could greatly reduce recurrence. To enable the nanoparticles (known as “nanoshells”) to target the inflammatory environment associated with endometriosis, they will be coated with phospholipid membranes derived from macrophages. Previous research has shown that various proteins present in macrophage membranes endow wrapped nanoparticles with both immune evasion capabilities (due to “markers-of-self” like CD47) and inflammation-targeting capabilities (enabled by proteins like PSGL-1, L-selectin, MAC-1, and others). Since endometriosis has high inflammation, we expect that macrophage membrane-wrapped nanoshells (Mac-NS) will accumulate in lesions more effectively than NS coated with the common passivating agent poly(ethylene glycol) (PEG-NS). In turn, photoacoustic imaging mediated by Mac-NS should have higher contrast and superior sensitivity compared to imaging mediated by PEG-NS. We will test these hypotheses in three aims, which will characterize the optical and physicochemical properties of Mac-NS and PEG-NS (Aim 1), compare their ability to target endometriotic versus non-diseased cells and enhance PAI contrast in vitro (Aim 2), and mediate the detection of intraperitoneal lesions in mice without associated toxicity (Aim 3). Demonstrating this technology can improve endometriosis visualization would be a major scientific breakthrough with potential for huge clinical impact.