Abstract 3911: Bacteriophage associated silicon particles (BASP) for targeting pancreatic neuroendocrine tumors

Abstract

Abstract The purpose of this project is to design and develop a multifunctional nanosystem for the diagnosis and treatment of pancreatic neuroendocrine tumors (PNETs). PNETs also known as Islet Cell Tumors are rare and slow-growing highly vascularized malignancies with an incidence rate of a thousand new cases per year. Their occurrence has increased five-fold within the past few decades and with surgery being the primary treatment modality, there is an immediate need to devise efficient diagnostic and therapeutic procedures. For this purpose, the synergistic tissue targeting capabilities of phage, optical and physical properties of gold nanoparticles (AuNP)/phage scaffold and the drug carrying potential of the hydrodynamically engineered silicon-based multistage nanovectors were employed to create the Bacteriophage Associated Silicon Particles (BASP). The BASP were characterized in vitro, optimized for in vivo imaging and are currently being investigated for therapeutic efficiency in vivo when loaded with Abraxane. CRKL is evaluated as a potential target expressed in the PNET microenvironment. CRKL targeting phage is incorporated into the BASP and the targeting capability is explored. Our data show that bacteriophage, displaying CRKL-recognizing peptide sequences, enhanced cellular association of BASP in human pancreatic cancer and murine microvascular endothelial cell lines. There is a significant increase in association of CRKL targeted BASP with endothelial cells as opposed to non-targeted assemblies mainly under the flow conditions with shear stresses similar these in the tumor vessels. Further, intravital microscopy studies in highly vascularized tumors demonstrated preferential accumulation of BASP in the tumor vasculature, based on their hydrodynamic characteristics and biological targeting. Overexpression of CRKL was confirmed in histological samples from PNET patients and mice with homozygous deletion of the Men1 gene in the pancreas (PNET model). MRI and CT imaging using CRKL targeted BASP loaded with SPION demonstrated that the systems can aid in detecting very small tumors using various imaging modalities. 3D CT images showed increasing density in the pancreatic tumor region in the mice for CRKL targeted BASP loaded with SPION treatment. Furthermore, the mice were imaged and validated the biodistribution and concentration of nanoparticles using a 9.4T MRI scanner. MRI images reveal nanoparticles accumulation in the region of tumor growth in the pancreas of mice at post-injection with CRKL targeted BASP loaded with SPION. This innovative multifunctional nanosystem has the potential to deliver a novel platform for both imaging and therapy for patients with PNETs as well as other cancers. Citation Format: Ziqiang Yuan, S Srinivasab, Jenolyn Francisca Alexander, X Liu, Wadih Arap, Renata Pasqualini, Mauro Ferrari, Steven K. Libutti, Biana Godin Vilentchouk. Bacteriophage associated silicon particles (BASP) for targeting pancreatic neuroendocrine tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3911.