Jenny T. Mac

Erythrocyte-derived nano-probes functionalized with antibodies for targeted near infrared fluorescence imaging of cancer cells.

Constructs derived from mammalian cells are emerging as a new generation of nano-scale platforms for clinical imaging applications. Herein, we report successful engineering of hybrid nano-structures composed of erythrocyte-derived membranes doped with FDA-approved near infrared (NIR) chromophore, indocyanine green (ICG), and surface-functionalized with antibodies to achieve molecular targeting. We demonstrate that these constructs can be used for targeted imaging of cancer cells in vitro. These erythrocyte-derived optical nano-probes may provide a potential platform for clinical translation, and enable molecular imaging of cancer biomarkers.

Light-based theranostics using hybrid structures derived from biological and organic materials

We have engineered hybrid nanostructures 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), as they are capable of generating heat, reactive oxygen species (ROS) or emit fluorescence light. We present preliminary results that demonstrate the effectiveness of NETs for fluorescence imaging and photodynamic therapeutic destruction of breast cancer cells, upon photo-excitation using NIR light. These hybrid nanostructures present a promising platform with theranostic capability for future biomedical clinical applications.

Erythrocyte-Derived Nanoparticles as a Theranostic Agent for Near-Infrared Fluorescence Imaging and Thrombolysis of Blood Clots

Ischemic stroke occurs when a blood clot obstructs or narrows the arteries that supply blood to the brain. Currently, tissue plasminogen activator (tPA), a thrombolytic agent, is the only United States Food and Drug Administration (FDA)-approved pharmacologic treatment for ischemic stroke. Despite its effective usage, the major limitation of tPA that stems from its short half-life in plasma (≈5 min) is the potential for increased risk of hemorrhagic complications. To circumvent these limitations, herein, the first proof-of-principle demonstration of a theranostic nanoconstruct system derived from erythrocytes doped with the FDA-approved near-infrared (NIR) imaging agent, indocyanine green, and surface-functionalized with tPA is reported. Using a clot model, the dual functionality of these nanoconstructs in NIR fluorescence imaging and clot lysis is demonstrated. These biomimetic theranostic nanoconstructs may ultimately be effective in imaging and treatment of blood clots involved in ischemic stroke.

Erythrocyte-Derived Theranostic Nanoplatforms for Near Infrared Fluorescence Imaging and Photodestruction of Tumors

Nanoparticles activated by near-infrared (NIR) excitation provide a capability for optical imaging and photodestruction of tumors. We have engineered optical nanoconstructs derived from erythrocytes, which are doped with the FDA-approved NIR dye, indocyanine green (ICG). We refer to these constructs as NIR erythrocyte-mimicking transducers (NETs). Herein, we investigate the phototheranostic capabilities of NETs for fluorescence imaging and photodestruction of SKBR3 breast cancer cells and subcutaneous xenograft tumors in mice. Our cellular studies demonstrate that NETs are internalized by these cancer cells and localized to their lysosomes. As evidenced by NIR fluorescence imaging and in vivo laser irradiation studies, NETs remain available within tumors at 24 h postintravenous injection. In response to continuous wave 808 nm laser irradiation at intensity of 680 mW/cm2 for 10-15 min, NETs mediate the destruction of cancer cells and tumors in mice through synergistic photochemical and photothermal effects. We demonstrate that NETs are effective in mediating photoactivation of Caspase-3 to induce tumor apoptosis. Our results provide support for the effectiveness of NETs as theranostic agents for fluorescence imaging and photodestruction of tumors and their role in photoinduced apoptosis initiated by their localization to lysosomes.

Effects of ICG concentration on the optical properties of erythrocyte- derived nano-vectors

Erythrocyte-based nanoparticle platforms can offer long circulation times not offered by traditional drug delivery methods. We have developed a novel erythrocyte-based nanoparticle doped with indocyanine green (ICG), the only FDA-approved near-infrared chromophore. Here, we report on the absorption and fluorescence emission characteristics of these nanoparticles fabricated using ICG concentrations in the range of 161-323 μM. These nanoparticles may serve as biocompatible optical materials for various clinical imaging and phototherapeutic applications.

Erythrocyte-derived optical nano-vesicles as theranostic agents

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).