We have engineered nano-vesicles, derived from erythrocytes, which can be doped with various near infrared (NIR) organic chromophores, including the FDA-approved indocyanine green (ICG). We refer to these vesicles as NIR erythrocyte-mimicking transducers (NETS) since in response to NIR photo-excitation they can generate heat or emit fluorescent light. Using biochemical methods based on reduction amination, we have functionalized the surface of NET with antibodies to target specific biomolecules. We present results that demonstrate the effectiveness of NETs in targeted imaging of cancer cells that over-express the human epidermal growth factor receptor-2 (HER2).
Optical nano-materials present a promising platform for targeted molecular imaging of cancer biomarkers and its
photodestruction. Our group is investigating the use of polymeric nanoparticles, loaded with indocyanine green, an FDA-approved
chromophore, as a theranostic agent for targeted intraoperative optical imaging and laser-mediated destruction
of ovarian cancer. These ICG-loaded nanocapsules (ICG-NCs) can be functionalized by covalent attachment of targeting
moieties onto their surface. Here, we investigate ICG-NCs functionalized with anti-HER2 for targeted fluorescence
imaging and laser-mediated destruction of ovarian cancer cells in vitro. ICG-NCs are formed through ionic cross-linking
between polyallylamine hydrochloride chains and sodium phosphate ions followed by diffusion-mediated loading with
ICG. Before functionalization with antibodies, the surface of ICG-NCs is coated with single and double aldehyde
terminated polyethylene glycol (PEG). The monoclonal anti-HER2 is covalently coupled to the PEGylated ICG-NCs
using reductive amination to target the HER2 receptor, a biomarker whose over-expression is associated with increased
risk of cancer progression. We quantify uptake of anti-HER2 conjugated ICG-NCs by ovarian cancer cells using flow
cytometery. The in-vitro laser-mediated destruction of SKOV3 cells incubated with anti-HER2 functionalized ICG-NCs
is performed using an 808 nm diode laser. Cell viability is characterized using the Calcein and Ethidium homodimer-1
assays following laser irradiation. Our results indicate that anti-HER2 functionalized ICG-NCs can be used as theranostic
agents for optical molecular imaging and photodestruction of ovarian cancers in-vitro.
Our group has constructed a new type of viral nanoparticles (VNPs) from genome-depleted plant infecting
brome mosaic virus (BMV) that encapsulates the FDA-approved near infrared (NIR) indocyanine green (ICG)[1]. We
refer to these VNPs as optical viral ghosts (OVGs) since the constructs lack the genomic content of wild-type BMV. One
of our areas of interest is the application of OVGs for real-time intraoperative NIR fluorescence imaging of small
peritoneal ovarian tumor nodules. We target human epidermal growth factor receptor-2 (HER-2) expression in ovarian
cancer as a biomarker associated with ovarian cancer, since its over-expression is linked to the disease’s progression to
death. We functionalize the OVGs with anti-HER-2 monoclonal antibodies using reductive amination methods. We used
fluorescence imaging to visualize the SKOV-3 cells (high HER-2 expression) after incubation with free ICG, OVGs, and
functionalized OVGs. Our results suggest the possibility of using anti-HER2 conjugated OVGs in conjunction with
cytoreductive surgery to detect small tumor nodules (<5cm) which currently are not excised during surgery.
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