A Carbon Nanodot Based Near-Infrared Photosensitizer with a Protein-Ruthenium Shell for Low-Power Photodynamic Applications

Abstract

Near-infrared (NIR) light-activated photosensitization represents an encouraging therapeutic method in photodynamic therapy, especially for deep tissue penetration. In this context, two-photon activation, i.e., utilization of photons with relatively low energy but high photon flux for populating a virtual intermediate state leading to an excited state, is attractive. This concept would be highly advantageous in photodynamic therapy due to its minimal side effects. Herein, we propose that the combination of plasma protein serum albumin (HSA) containing several Ru complexes and NIR two-photon excitable carbon nanodots (Cdots), termed HSA-Ru-Cdots, provides several attractive features for enhancing singlet oxygen formation within the mitochondria of cancer cells stimulated by two-photon excitation in the NIR region. HSA-Ru-Cdot features biocompatibility, water solubility, and photostability as well as uptake into cancer cells with an endosomal release, which is an essential feature for subcellular targeting of mitochondria. The NIR two-photon excitation induced visible emission of the Cdots allows fluorescence resonance energy transfer (FRET) to excite the metal-to-ligand charge transfer of the Ru moiety, and fluorescence-lifetime imaging microscopy (FLIM) has been applied to demonstrate FRET within the cells. The NIR two-photon excitation is indirectly transferred to the Ru complexes, which leads to the production of singlet oxygen within the mitochondria of cancer cells. Consequently, we observe the destruction of filamentous mitochondrial structures into spheroid aggregates within various cancer cell lines. Cell death is induced by the long-wavelength NIR light irradiation at 810 nm with a low power density (7 mW/cm2), which could be attractive for phototherapy applications where deeper tissue penetration is crucial.

Carbon dots as a novel photosensitizer for photodynamic therapy of cancer and bacterial infectious diseases: recent advances

“…HSA-Ru-Cdot had mitochondrial subcellular targeting capabilities and was taken up by cancer cells via intranuclear body release. Cell viability of A549, HeLa was reduced by 22%-55% at 15 min of 810 nm LED light irradiation (7 mW/cm 2 ) and these results provided a promising direction for PDT [114].…”

Near-Infrared Dyes: Towards Broad-Spectrum Antivirals

“…The aim of this review was to identify structural types of NIR dyes with potential for use in photodynamic virus inactivation. In this work, we limited ourselves to lowmolecular-weight organic compounds without considering biopolymers, polymers [66][67][68], nanoparticles [69][70][71], and other NIR-absorbing and singlet oxygen-generating compounds and conjugates [16,[72][73][74] that have been proposed for PDT, including viral infections [75], in recent years. Despite the considerable attention that NIR dyes have attracted as agents for PDT, their use for virus inactivation is far less common.…”