Indocyanine Green Loaded Nanoconstructs for Optical Imaging and Phototherapeutic Applications.

摘要

Development of theranostic nano-constructs may enable diagnosis and treatment of diseases at high spatial resolution. Optically active nanoparticles are widely pursued as exogenous chromophores in diagnostic imaging and phototherapeutic applications. However, the blood circulation time of nanoparticles remains limited due to the rapid clearance of the nanoparticles by reticuloendothelial system (RES). Coating with Polyethylene glycol (PEG) is a strategy to extend the circulation time of nanoparticles. Here, we report PEGylation of polymeric-based nanocapsules loaded with Indocyanine green (ICG) and effect of PEG's molecular weight on the uptake of these nanocapsules by human spleen macrophages and hepatocytes using flow cytometry. To characterize the biodistribution of the constructs, we performed in vivo quantitative fluorescence imaging in mice and subsequently analyzed the various extracted organs. Our results suggest that encapsulation of ICG in these PEGylated constructs is an effective approach to prolong the circulation time of ICG and delay its hepatic accumulation. Increased bioavailability of ICG, offers the potential of extending the clinical applications of ICG. Targeted delivery of therapeutic and imaging agents using surface modified nanovectors has been explored immensely in recent years. The growing demand for site-specific and efficient delivery of nanovectors entails stable surface conjugation of targeting moieties. Our ICG-loaded polymeric nanocapsules (ICG-NCs) have potential for covalent coupling of various targeting moieties and materials due to presence of amine groups on the surface. Here, we covalently bioconjugate PEG-coated ICG-NCs with monoclonal anti- HER2 through reductive amination-mediated procedures. The targeting abilities of HER2 functionalized ICG-NCs toward ovarian cancer was investigated in-vitro. Since these functionalized nanoconstructs have potential applications in laser-induced photodestruction of ovarian cancer cells, we studies NIR laser induced phototherapy of ovarian cancer cells in-vitro. Other than polymeric theranostic nano-constructs, here we demonstrate the first successful engineering of hybrid nano-scale constructs derived from membranes of hemoglobin-depleted erythrocytes that encapsulate ICG. We show the utility of the constructs as photo-theranostic agents in fluorescence imaging and photothermal destruction of human cells. These erythrocyte-mimicking nano-structures can be derived autologously, and may have broad applications in personal nanomedicine ranging from imaging and photo-destruction of cancerous tissues to vascular abnormalities, and longitudinal evaluations of therapeutic interventions.