Noble metal nanoparticles modified by cyanines and stilbenes for enhanced signal optical tomography and hyperthermal therapy

The report describes the synthesis of core-shell noble metal anisotropic nanoparticles modified with cyanine-class fluorophores and stilbene-based Raman reporters. In perspective, it may be used for optical diagnostics and therapeutic hyperthermia. Modern chemistry of optical tags offers solutions for invasive biomedical optical diagnostics and therapy methods such as Raman and SERS labeling, immune fermentative reaction utilizing fluorescent reporter and tomography with vectors-conjugated fluorophores, photodynamic and hyperthermal therapy. The last method consists in using of energy dissipated by particle to overheat neighboring tumor cells leading to their death and has two different implementations: the first is based on the superparamagnetic nanoparticles together with NMR excitation while the second one utilizes lasers to excite the plasmonic nanoparticles. There is a proble related to ability of using visible light in diagnostics and treatment to see things with naked eyes: light passing through biological tissues undergoes absorption and scattering. Thus, it is hard to see definite shape of the luminous region, especially if it is at a depth. For this reason, fluorescence tomography and photodynamic therapy are applied only to superficial tissues. The present study is devoted to development of nanocomposite tags for optical tomography with improved capability for determining the size, shape and location of malignant tumors. The idea of the research is to use the plasmon resonance effect. The plasmon resonance effect is the ability of noble metal nanoparticles to absorb visible and near infrared light. In this way, the generated local electromagnetic field of nanoparticles leads to hyperpolarization of neighboring molecules, the scattering intensity of which increases by orders of magnitude compared to the usual one. Fig. 1. Schematic representation of conception Gold and silver nanoparticles of anisotropic shape (nanorods, nanoprisms and nanobones) were synthetized, the plasmon resonance peak of which is shifted to the red border of the visible spectrum range. This region is also known as the region of transparency of biological tissues. The region of 600-700 nm refers to visible light, so red light emission can be observed with naked eyes, thus the developed tags may be applied directly during surgical intervention These nanoparticles were modified with cyanine-based fluorophores (e.g. Cy 5.5 and Cy 7) and Raman reporters (e.g. 4,4'-dimercaptostilbene, 4,4'-diaminostilbene) and subsequently coated with a silica dioxide shell using the Strober method. The principal scheme of optically responsive nanotag conjugated to a delivery vector is shown on Fig. 1. Translational Biophotonics: Diagnostics and Therapeutics, edited by Zhiwei Huang, Lothar D. Lilge, Proc. of SPIE-OSA Vol. 11919, 119192E · © 2021 OSA-SPIE CCC code: 1605-7422/21/$21 · doi: 10.1117/12.2615046 Proc. of SPIE-OSA Vol. 11919 119192E-1 Fig. 2. Comparison of the fluorescence spectra obtained from gold nanobones modified with various polymeric shells with incorporated cyanine 5.5. Dr. Liz-Marzan proposed layer-by-layer coating of nanoparticles with polyectrolytes to obtain polyvinylpirrolydone shell, which is common substrate for silica dioxide composition according to the Strober’s method. This core-shell protocol, applied to nanobone-shaped gold nanoparticles (distorted nanorods) modified by Cy5.5, resulted in emission quenching (Fig. 2., pink curve, which is indistinguishable from purple one, which is the control sample without dye). Considering that the chemical quenching effect depends on a distance from surface, we placed the chromophore between the second (polyallylamine ammonium) and the third (polyvinylpirrolydone) polyelectrolyte layers, and finally observed a strong emission (Fig. 2., green curve). The signal remains after subsequent modification of the silica dioxide shell with aminopropyltrimethoxysilane and folic acid conjugation with its terminal carboxyl group. Our target is folate receptor, which is overexpressed in tumor cells. At the moment, work is underway to test obtained core-shell nanoparticles on biological samples.