Abstract 1952: Tumor microenvironment targeted Rosella nanoparticle for the detection of triple negative breast cancer by multispectral optoacoustic tomography
Authors: Samykutty Abhilash , McNally Molly , Thomas Alexandra , Grizzle William , McNally Lacey R. 
Published: August 2019

Purpose: Recent advances in the nanotechnology and molecular imaging provides an excellent opportunity for development of delivery vehicles and imaging probes to improve real-time assessment and early detection of breast cancer progression.The absence of estrogen receptor (ER), progesterone receptor (PR), or HER-2 genes, represents a major clinical challenge for triple negative breast cancer (TNBC). Because of the absence of reliable markers, there is an unmet clinical need for developing efficient methods to identify TNBC. We have developed an acidic pH targeted Rosella nanoparticles that can actively release IR780 dye into orthotopically implanted TNBC tumors to improve tumor detection using multispectral optoacoustic imaging technology (MSOT).

Methods: The Rosella nanoparticles are a mesoporous silica base with wormhole pore architecture containing a chitosan gatekeeper and V3 pHLIP targeting peptide. The particles were synthesized using the sol-gel method and characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The Rosella particles were loaded with propidium Iodide (PI) or IR780 infrared imaging dye to evaluate pH-sensitive cargo release. Female athymic mice were implanted with MDA-MB-468 breast cancer cells by the mammary fat pad injection. Once the tumor reaches 3mm in size, athymic mice were intravenously injected with ROSELLA nanoparticles carrying IR780 dye and were imaged with MSOT.

Results: We have synthesized the Rosella nanoparticle with wormhole pores that is 27 nm diameter and can encapsulate the IR780 imaging probes for the detection of the TNBC. The Rosella particle contains a chitosan gatekeeper which can degrade upon contact with acidic pH tumor to prevent off-target release and is further sensitized to pH using V3 peptide. The Rosella nanoparticles can detect acidic tumor microenvironment and can penetrate inside the tumor cells. As a model of TNBC, we have injected MDA-MB-468 cells into the mammary fat pad of the female athymic mice to develop breast tumors. Once the tumor reached 3mm in size, we have intravenously delivered ROSELLA nanoparticles to the athymic mice with TNBC tumors. Our results were demonstrated that the intravenous injection of the ROSELLA particles could detect the orthotopically implanted TNBC tumors (p&lt;0.0001,n=5).

Conclusion: most aggressive subtypes of breast cancer, TNBC has a poor response for majority of the FDA-approved breast cancer drugs. To overcome these limitations, the distinct nanoformulations with potent imaging technology will enable to develop tumor-penetrating nanoparticles to more effectively deliver chemotherapeutics or imaging agents with least off-target effects. Future translation of these technologies has a high clinical impact concerning our current treatment options for TNBC patients.

Citation Format: Abhilash Samykutty, Molly McNally, Alexandra Thomas, William Grizzle, Lacey R. McNally. Tumor microenvironment targeted Rosella nanoparticle for the detection of triple negative breast cancer by multispectral optoacoustic tomography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1952.