Abstract 1937: pH-responsive tumor-targeted mesoporous silica nanoparticle for the identification of pancreatic cancer using optoacoustic tomography

Autor: Lacey R. McNally, Abhilash Samykutty, Kylie Nairon, William MacCuaig, Molly W. McNally, William E. Grizzle, Surya R. Banks
Rok vydání: 2019
Předmět:
Zdroj: Cancer Research. 79:1937-1937
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2019-1937
Popis: Purpose: Due to inadequate early detection and inability to operate at advanced stages, pancreatic ductal adenocarcinoma (PDAC) has remained one of the most difficult types of cancer to treat. A small range of non-specific symptoms coupled with quick metastasis rate result in a poor 5-year survival rate; 14% for those diagnosed within stage IA, and as low as 1% for those diagnosed during stage IV. Nanoparticles have recently emerged as a potential delivery agent for diagnostic and therapeutic agents, and although clinical success has not been ample due to targeting accuracy issues. This work shows a nanoparticle that has been functionalized with a pancreatic cancer-specific targeting ligand and exhibits specific particle release in pancreatic malignant environment (pH 6.6) as compared to non-malignant environments (pH 7.4). Methods: Wormhole-pored mesoporous silica nanoparticles were formed at 80°C using Tetrapropyl orthosilicate (TPOS) and a scaffold of hexadecyltrimethyl-ammonium bromide (CTAB). Acetic acid and ethanol were used in dialysis procedures to remove the CTAB scaffold and create worm-like pores. Chitosan was added to coat the silica particles and serve as a gatekeeper. IR-780 was added before the solution was acidified to load the dye into the worm-hole particles created. Shortly after, the solution pH was raised back to physiological levels (pH=7.4) to trap the dye within the particle. The particle surfaces were functionalized to attach a targeting ligand pH-low insertion peptide (V7) to conjugate the dye-loaded nanoparticles. Pancreatic adenocarcinoma cells (S2VP10 line) were plated in pH-7.4,6.8, and 6.6 PBS solutions with the loaded particles to assess uptake via near-infrared fluorescence and multispectral optoacoustic imaging. Results: Zeta potential and dynamic light scattering were used to ensure the 63nm size nanoparticle and proper coating. Near-infrared fluorescence imaging showed ~10X increased signal at pH 6.6 as compared to pH=7.4. MSOT imaging ~5X increased signal in the malignant microenvironment environment that is acidic as compared to the non-malignant environment at pH 7.4. Conclusion: The functionalized wormhole mesoporous silica nanoparticles coated with chitosan demonstrated pH-sensitivity in terms of cellular uptake via NIR fluorescence and MSOT imaging. Citation Format: William MacCuaig, Abhilash Samykutty, Molly McNally, Kylie Nairon, Surya Banks, William Grizzle, Lacey R. McNally. pH-responsive tumor-targeted mesoporous silica nanoparticle for the identification of pancreatic cancer using 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 1937.
Databáze: OpenAIRE
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