We report novel bioconjugated nanosensitizers as optical and therapeutic probes for the detection, monitoring and
treatment of cancer. These nanosensitisers, consisting of hypericin loaded bioconjugated gold nanoparticles, can act as
tumor cell specific therapeutic photosensitizers for photodynamic therapy coupled with additional photothermal effects
rendered by plasmonic heating effects of gold nanoparticles. In addition to the therapeutic effects, the nanosensitizer can
be developed as optical probes for state-of-the-art multi-modality in-vivo optical imaging technology such as in-vivo 3D
confocal fluorescence endomicroscopic imaging, optical coherence tomography (OCT) with improved optical contrast
using nano-gold and Surface Enhanced Raman Scattering (SERS) based imaging and bio-sensing. These techniques can
be used in tandem or independently as in-vivo optical biopsy techniques to specifically detect and monitor specific
cancer cells in-vivo. Such novel nanosensitizer based optical biopsy imaging technique has the potential to provide an
alternative to tissue biopsy and will enable clinicians to make real-time diagnosis, determine surgical margins during
operative procedures and perform targeted treatment of cancers.
Photodynamic diagnosis (PDD) exploits the photoactive nature of certain compounds, namely photosensitizers, in order
to enhance the visual demarcation between normal and neoplastic tissue. Hypericin is one such potent photosensitizer
that preferentially accumulate in neoplastic tissue, and fluoresce in the visible spectrum when illuminated with light of an
appropriate wavelength. In our study, we investigated the role of E-cadherin in the selective permeation of hypericin in
bladder cancer tissues. Clinical studies were done on a series of 43 histologically graded bladder cancer biopsy
specimens, obtained from 28 patients who received intravesical instillations with 8μM hypericin solution for at least 2
hours. Immunohistochemical staining was used to assess the expression of E-cadherin, in the cryosectioned tissues.
Hypericin uptake was examined by fluorescence microscopy. Immunohistochemical staining showed a clear expression
of E-cadherin along the urothelial lining of the normal and pre-malignant tissues. Partial expression of these cell
adhesion molecules were still observed in malignant tissues, however there was a loss of expression to variable extends
along the urothelium. Thus, loss of intercellular adhesion can be associated with enhanced hypericin permeation through
paracellular diffusion.
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