Optical Characteristics and Tumor Imaging Capabilities of Near Infrared Dyes in Free and Nano-Encapsulated Formulations Comprised of Viral Capsids

Abstract

Near infrared (NIR) fluorescent molecules and nanosized structures can serve as potential optical probes for image-guided removal of small tumor nodules (≲ 1 mm diameter). Although indocyanine green (ICG) remains as the only FDA-approved NIR dye, other organic dyes are under extensive development for enhanced imaging capabilities. One such dye is BrCy106-NHS where bromine is substituted for aromatic structures in cyanine dyes. Herein, we investigate the absorption and fluorescence characteristics of ICG and BrCy106-NHS, and quantitatively assess their tumor imaging capabilities in free (non-encapsulated) and a nano-encapsulated form that utilizes the capsid protein (CP) from genome-depleted plant-infecting brome mosaic virus as the encapsulating shell. We refer to these nanoconstructs as optical viral ghosts (OVGs). For example, when fabricated at CP to dye concentration ratio of 200, value of the spectrally integrated fluorescence emission for BrCy106-NHS-doped OVGs is ∼60 times higher than that of ICG-doped OVGs. Our analysis of homogenized mice intraperitoneal tumors indicate that the averaged total fluorescence emission associated with the use of BrCy106-NHS-doped can be at least about 44 times greater than that of ICG-doped OVGs. Our results suggest that OVGs containing BrCy106-NHS may potentially serve as effective optical probes for tumor imaging.

Intravital Vascular Phototheranostics and Real-Time Circulation Dynamics of Micro- and Nanosized Erythrocyte-Derived Carriers

“…Nano-sized carriers with dimensions <200 nm are relevant for the delivery of imaging and/or therapeutic agents to tumors since such carriers can extravasate out of the vasculatures and accumulate at tumor sites by the enhanced permeability and retention effect resulting from leaky tumor vasculature and impaired lymphatic drainage. 1 Various carrier systems such as polymeric particles, [2][3] liposomes, 4 genome-depleted brome mosaic virus, [5][6] and inorganic nanoplatforms 7 have been investigated. 8 For conventional nonstealth particles, opsonin proteins present in the blood serum bind to the particles, resulting in recognition and removal of the particles by the reticuloendothelial system and shortening their blood circulation time.…”

Crystal structures and Hirshfeld analysis of 4,6-dibromoindolenine and its quaternized salt

“…In particular, fluorescent dyes with bromine atoms are utilized for photodynamic therapy applications (Atchison et al, 2017;Liu et al, 2021). Moreover, cyanine with the 4,6dibromoindolenine moiety indicates excellent properties for optical tumor imaging by its fluorescence (Guerrero et al, 2017).…”

Near-Infrared-Fluorescent Erythrocyte-Mimicking Particles: Physical and Optical Characteristics

“…This sandwich-like, - stacking of individual ICG molecules results in interaction of the individual transition dipole moments that raises the excited-state energy to produce a blueshifted absorption peak [49,73,74]. In water, even relatively low concentrations of ICG (> 10 M) will begin to form Haggregates [74,85].…”

“…Encapsulation can also serve to enhance the stability of ICG, which can degrade due to heat or optical exposure [43,44]. To date, various materials have been used to encapsulate ICG, including polymers [45,46], plant-virus capsids [47][48][49], and liposomes [50,51].…”