Erythrocyte-Derived Optical Constructs for Biomedical Imaging and Phototherapy
Light-activated theranostic materials offer a potential platform for biomedical imaging and phototherapeutic applications. We have engineered constructs derived from erythrocytes, which can be doped with the FDA-approved near infrared (NIR) dye, indocyanine green (ICG). We refer to these constructs as NIR erythrocyte-mimicking transducers (NETs) since once activated by NIR light, NETs can transduce the absorbing photons energy to generate heat, emit fluorescence, or mediate production of reactive oxygen species.
In a series of studies, we examined the phototheranostic capabilities of NETs for phototherapy of port wine stains and fluorescence imaging and phototherapy of cancer. Specifically, we measured and sequentially used the optical properties of NETs to theoretically investigate the effectiveness of NETs in mediating photothermal destruction of port wine stain blood vessels. Next, we investigated the phototheranostic capabilities of NETs for fluorescence imaging and photodestruction of SKBR3 breast cancer cells and subcutaneous xenograft tumors in mice. Lastly, we present ovarian tumor imaging using NETs and spatially modulated illumination.
The optical characterization and mathematical modeling results can be used in guiding the fabrication of NETs with patient-specific optical properties to allow for personalized treatment based on the depth and size of blood vessels and pigmentation of the individual’s skin. Whereas, our in vitro and in vivo results provide support for the effectiveness of NETs as theranostic agents for structured fluorescence imaging and photodestruction of tumors.
Our results demonstrate that for a given NETs diameter, absorption increased over the approximate spectral band of 630–860 nm with increasing ICG concentration and that changing the ICG concentration minimally affected the scattering characteristics. Our simulation results indicated that blood vessels containing micron- or nano-sized NETs and irradiated at 755 nm had higher levels of photothermal damage as compared to blood vessels without NETs irradiated at 585 nm.
In response to continuous wave 808 nm laser irradiation at intensity of 680 mW/cm2 for 10−15 min, NETs mediated the destruction of cancer cells and tumors in mice through synergistic photochemical and photothermal effects. Our spatially modulated illumination imaging results demonstrated enhanced contrast and through the use of various frequency modulations.