Abstract 1858: Theranostic nanoparticles for detection and treatment of pancreatic cancer

Abstract

Abstract Background: Despite continued efforts to improve early detection and treatment of pancreatic adenocarcinoma, the disease still carries a poor prognosis. The combination of multispectral optoacoustic tomography (MSOT) and theranostic nanoparticles offers a possible solution by providing tumor targeting using fluorescent dyes and treatment through drug delivery. We describe a 40 nm colloidal mesoporous silica nanoparticle (CMS) with vermiform pores and a chitosan coating and tagged with the V7 peptide to provide pH-specific dual targeting to deliver a contrast agent in a tumor-specific fashion. Methods: CMSs were synthesized using a modified Stober method, coated with chitosan, and conjugated with a V7 peptide, resulting in a dual acidic pH targeting system. Particle characterization was performed using transmission electron microscopy (TEM), UV-vis spectrophotometry, Zeta potential, and dynamic light scattering . To determine acidic pH specificity of V7-CMS, Panc1 and S2VP10 cell lines were incubated in cell culture medium at either pH 7.4 or 6.6 followed by treatment with V7-CMS. Particle uptake was determined using near infrared (NIR) fluorescence and tissue phantoms. Finally, for in vivo testing, the same CMSNs were injected into mice bearing S2VP10 pancreatic tumors. MSOT imaging was performed 8 hours after CMS injection. Results: TEM images demonstrated successful synthesis of approximately 40 nm V7-CMSs with vermiform pores. On NIR imaging, V7-CMS demonstrated acidic pH specificity in both S2VP10 and Panc 1 cells at pH 6.6, with particle localization and signal intensity 8-fold and 5-fold higher, respectively, than that observed at pH 7.4. In tissue phantoms, increased pH specificity was also observed in both S2VP10 and Panc 1 cells at pH 6.6. Particle location and signal intensity on MSOT was 20-fold and 4-fold higher, respectively, than that observed at pH 7.4. In the murine orthotopic S2VP10 pancreatic tumor model, MSOT imaging 8 hours after IV CMS injection demonstrated V7-CMS accumulation specifically within pancreatic tumors. Conclusion: The acidic pH specific dual targeting system using chitosan-coated and pHLIP V7-tagged CMSs results in tumor specificity. Preferential binding and dye release was increased as much as 20-fold at pH 6.6 as compared to pH 7.4 in tissue phantoms. MSOT was able to detect tumor specific accumulation of V7-CMS in vivo. These small, pH specific particles hold significant promise for effectively identifying pancreatic tumors with high sensitivity and specificity and for targeted drug delivery. Note: This abstract was not presented at the meeting. Citation Format: Phillip Chuong, Neal Bhutiani, Lacey R. McNally. Theranostic nanoparticles for detection and treatment of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1858. doi:10.1158/1538-7445.AM2017-1858