Abstract 4122: Acidic tumor microenvironment targeted wormhole-shaped mesoporous silica nanoparticles to detect ovarian cancer by multispectral optoacoustic tomography
Authors: Samykutty Abhilash , McNally Molly W. , Grizzle William E. , Chiba Akiko , Thomas Alexandra , McNally Lacey R. 
Published: August 2018

Purpose: The implementation of the innovative technologies remains the top priority for the development of potential modalities for the diagnosis and treatment of various cancers. Despite all the recent advances, ovarian cancer is considered as a lethal gynecologic malignancy in which vast majority of the cases are diagnosed at the late metastatic stage at which the prognosis is poor. Because of the few apparent early symptoms, significant effort was made for developing efficient methods to identify early progression of the disease. We demonstrated that the bioconjugation of the V7 peptide on 27nm wormhole mesoporous silica nanoparticles (V7-CWMSN) particles specifically release the IR780 imaging probe at the orthotopically implanted early-stage ovarian tumor to detect by multispectral optoacoustic imaging technology (MSOT).

Methods: Wormhole mesoporous silica nanoparticles (WMSN) were synthesized by sol-gel chemistry. The WMSN were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The surface of the WMSN particle was functionalized with pH sensitizer chitosan to obtain CWMSN. The CWMSN particle was loaded with propidium Iodide (PI) or IR780 infrared imaging dye. Further, the conjugation of the CWMSN with V7 pHLIP peptide (V7-CWMSN) developed pH sensitive cargo release from the nanoparticles. Female athymic mice were orthotopically implanted with ES-2 ovarian cancer cells. Following 10 days of orthotopic implantation of the tumor cells, mice were intravenously injected with V7-CWMSN particles containing IR780 dye and were imaged with MSOT.

Results: In the current study, we have synthesized the wormhole-shaped mesoporous silica particles (WMSN) with the 27 nm diameter carrying IR780 imaging probes for the detection of early-stage ovarian cancer. The V7 peptide undergoes a conformational change upon contact with the acidic tumor microenvironment. Also, the chitosan crosslinking on the surface of the particles (V7-CWMSN) acts as a gatekeeper that is degradable upon contact with acidic pH tumor to prevent off-target release. As a model for ovarian cancer, we have used athymic mice orthotopically implanted with ovarian cancer cells. This model closely resembles the human ovarian cancer pathophysiology. Our results have demonstrated that the intravenous delivery of V7-CWMSN particles could detect the orthotopically implanted early-stage ovarian tumors (p&lt;0.0001,n=5).

Conclusion: The development of the distinct nanoformulations with potent imaging technology enables the visualization of early-stage ovarian tumors. Translating these modalities may allow clinicians to identify early-stage malignancies that are currently undetectable through conventional imaging techniques.

Citation Format: Abhilash Samykutty, Molly W. McNally, William E. Grizzle, Akiko Chiba, Alexandra Thomas, Lacey R. McNally. Acidic tumor microenvironment targeted wormhole-shaped mesoporous silica nanoparticles to detect ovarian cancer by multispectral optoacoustic tomography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4122.