Abstract 4664: Enzymatically-responsive tumor-targeted mesoporous silica nanoparticle for identification of pancreatic cancer

Abstract

Abstract Purpose: Pancreatic cancer remains an unsolved health issue, with its rapid progression and resistance to modern therapy leading to poor prognoses for most patients. The prevalence of metastasis in pancreatic cancer makes complete tumor location and removal rare, and those who do have resectable disease have only a 20% 5-year survival rate. In recent years, nanoparticles have been explored as targeted delivery agents for chemotherapeutic drugs and imaging dyes, however few have achieved clinical success due to overestimation of biological phenomena and reliance on passive targeting systems. In this work, an enzyme-responsive nanoparticle has been developed for increased active pancreatic tumor targeting and specific release at biologically-significant enzyme concentrations. Methods: Mesoporous silica nanoparticles were formed using a scaffold of hexadecyltrimethylammonium bromide (CTAB) at 80°C. The scaffold was removed to form wormhole-like pores using a series of dialysis procedures. Transmission electron microscopy (TEM) confirmed the 35 nm diameter and porous structure of the particles. The particles were then loaded with IR780 dye, and surfaces were functionalized with (3-aminopropyl) triethoxysilane (APTES). The loaded particles were then encapsulated with a combination of Type A and Type B gelatin, followed by a stabilizing polyvinylpyrrolidone (PVP) layer. Dynamic light scattering (DLS) and zeta potential were used to confirm coating. Coated particle samples were exposed to collagenase type IV (MMP-9) enzyme to test encapsulation efficiency and enzyme sensitivity. Enzyme-treated and intact samples were transferred to tissue phantoms, and Multispectral optoacoustic tomography (MSOT) was used for comparative analysis. Results: TEM confirmed the formation of stable 35 nm silica nanoparticles with a wormhole-like pore structure. Zeta potential decrease from 55 mV to 5 mV and DLS particle diameter increase from 35 nm to 334.5 nm indicated binding of gelatin and PVP to particle surfaces. MSOT imaging showed 10 X increased signals from untreated nanoparticles as compared to enzyme-treated nanoparticles, indicating that dye molecules remained inside the pores of coated particles and were released when exposed to MMP-9. Conclusion: Gelatin/PVP-coated mesoporous silica nanoparticles encapsulated dye and demonstrated MMP-9 activated dye release at biologically-relevant enzyme concentrations. Citation Format: Kylie Nairon, Abhilash Samykutty, Molly W. McNally, Girish Mishra, William E. Grizzle, Lacey R. McNally. Enzymatically-responsive tumor-targeted mesoporous silica nanoparticle for identification of pancreatic cancer [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 4664.