Identification of pancreatic tumors in vivo with ligand-targeted, pH responsive mesoporous silica nanoparticles by multispectral optoacoustic tomography

Despite significant efforts to translate nanotechnology for cancer application, lack of identification of biodistribution/accumulation of these nanovehicles in vivo remains a substantial barrier for successful implementation of theranostic nanoparticles in the clinic. The purpose of the study was to...

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Bibliographic Details
Published in:Journal of controlled release 2016-06, Vol.231, p.60-67
Main Authors: Gurka, Marie K., Pender, Dillon, Chuong, Phillip, Fouts, Benjamin L., Sobelov, Alexander, McNally, Molly W., Mezera, Megan, Woo, Shiao Y., McNally, Lacey R.
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Chitosan - chemistry
Deoxycytidine - analogs & derivatives
Deoxycytidine - chemistry
Deoxycytidine - pharmacology
Drug Liberation
Female
Humans
Hydrogen-Ion Concentration
Indocyanine Green - chemistry
Ligands
Mesoporous silica
Mice
Nanomedicine multispectral optoacoustic tomography
Nanoparticles - chemistry
Pancreatic cancer
Pancreatic Neoplasms - diagnostic imaging
Pancreatic Neoplasms - drug therapy
Particle Size
Photoacoustic Techniques - methods
Porosity
Rats, Nude
Silicon Dioxide - chemistry
Surface Properties
Theranostic Nanomedicine
Theranostics
Tissue Distribution
Tomography - methods
Urokinase-Type Plasminogen Activator - metabolism
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Summary:Despite significant efforts to translate nanotechnology for cancer application, lack of identification of biodistribution/accumulation of these nanovehicles in vivo remains a substantial barrier for successful implementation of theranostic nanoparticles in the clinic. The purpose of the study was to develop a tumor-targeted theranostic nanovehicle for pancreatic cancer detectable by multispectral optoacoustic tomography (MSOT). To improve the tumor specificity of our mesoporous silica nanoparticle (MSN), we utilized a dual targeting strategy: 1) an elevated tumor receptor, urokinase plasminogen activator receptor (UPAR), and 2) the acidic tumor microenvironment. The tumor specificity of the MSN particle was improved with the addition of both chitosan, targeting acidic pH, and urokinase plasminogen activator (UPA), targeting UPAR. Drug release assays confirmed pH responsive release of gemcitabine in vitro. The UPAR specific binding of MSN-UPA nanoparticles was confirmed by reduction in fluorescence signal following MSN-UPA nanoparticle treatment in UPAR positive cells blocked with a UPAR-blocking antibody. Based upon Indocyanine Green encapsulation within the nanoparticles, UPA ligand targeted MSNs demonstrated increased intensity compared to untargeted MSNs at both pH7.4 (7×) and 6.5 (20×); however the signal was much more pronounced at a pH of 6.5 using tissue phantoms (p
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2015.12.055