Multiphoton and harmonic generation imaging methods enable direct visualization of drug nanoparticle carriers in conjunction with vasculature in fibrotic prostate tumor mouse model

Thomas Abraham, Gary A. Clawson, Christopher O. McGovern, Wade Edris, Xiaomeng Tang, James H. Adair, Gail L. Matters

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

Abstract

Prostate cancer (PCA) is the most common cancer and the third most common cause of cancer death in men. Targeted nanoparticles (NPs) that deliver effective doses of chemotherapeutic drugs specifically to PCA could improve chemotherapy efficacy without the toxicities. In the relevant mouse models, the direct visualization of such drug nanoparticles along with the vasculature and fibrillar collagen matrix at submicron resolution are critically important for the accurate measurements of the drug distribution in the tissue matrix. Multiphoton microscopy, which uses ultra-short IR laser pulses as the excitation source, produces multiphoton excitation fluorescence (MPEF) signals from exogenous or endogenous fluorescent proteins and induces specific second harmonic generation (SHG) signals from non-centrosymmetric proteins such as fibrillar collagens. The objective here is to visualize and quantify the 3D distribution of an aptamer conjugated calcium phosphosilicate based drug nanoparticle carriers along with vasculature and tissue matrix in ex vivo thick mouse prostate tumor tissue with submicron resolution. Human prostate tumor xenografts were established in athymic mice by injecting prostate cell line derived from human (PC-3 cells) and were grown for 4 weeks. Near-infrared imaging agent indocyanine green (ICG) loaded calcium phosphosilicate nanoparticles (CPSNPs) including targeted CPSNPs bioconjugated with DNA Aptamer, empty non-ICG containing CPSNPs (Ghost) and Dil (for blood vessel painting) were injected into the tail vein. The spectral unmixing was performed to extract Dil signal from ICG signal using measured emission spectra. The 3D reconstructions and subsequent quantitation showed accumulation of ICG in blood capillaries versus tissue matrix. We here conclude that this multiphoton based multimodal imaging approach can provide spatially resolved 3D images with spectral specificities that are sensitive enough to identity and quantify the distributions of drug nanoparticle carriers in conjunction with vasculature and tissue matrix in prostate tumor with structural precision.

Original languageEnglish (US)
Title of host publicationImaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII
EditorsAttila Tarnok, James F. Leary, Daniel L. Farkas
PublisherSPIE
ISBN (Electronic)9781510624047
DOIs
StatePublished - Jan 1 2019
EventImaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII 2019 - San Francisco, United States
Duration: Feb 4 2019Feb 6 2019

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume10881
ISSN (Print)1605-7422

Conference

ConferenceImaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII 2019
CountryUnited States
CitySan Francisco
Period2/4/192/6/19

All Science Journal Classification (ASJC) codes

  • Electronic, Optical and Magnetic Materials
  • Atomic and Molecular Physics, and Optics
  • Biomaterials
  • Radiology Nuclear Medicine and imaging

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    Abraham, T., Clawson, G. A., McGovern, C. O., Edris, W., Tang, X., Adair, J. H., & Matters, G. L. (2019). Multiphoton and harmonic generation imaging methods enable direct visualization of drug nanoparticle carriers in conjunction with vasculature in fibrotic prostate tumor mouse model. In A. Tarnok, J. F. Leary, & D. L. Farkas (Eds.), Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII [108811T] (Progress in Biomedical Optics and Imaging - Proceedings of SPIE; Vol. 10881). SPIE. https://doi.org/10.1117/12.2508833