AIEgens Conjugation Improves the Photothermal Efficacy and Near-Infrared Imaging of Heptamethine Cyanine IR-780

Abstract

Near-infrared (NIR) fluorescent probes can deeply penetrate through tissues with little damage. To facilitate image-guided theranostics, researchers usually apply a desired amount of photosensitizers to achieve effective photothermal responses. However, these probes could easily suffer from low photostability and aggregated-caused quenching effect in high concentrations. In this paper, the rational incorporation of an aggregated-induced emission (AIE) unit into the structure of heptamethine cyanine IR-780 is reported. Using tetraphenylethene (TPE) as an AIE core, we synthesize three TPE-modified IR-780 probes (IR-780 AIEgens) via different linkages. The IR-780 derivatives all show enhanced AIE features, in which the probe with an ether linkage (IR780-O-TPE) is superior in rapid cell uptake, high targeting capacity, and good photostability. Moreover, IR780-O-TPE exhibits the strongest cytotoxicity to HeLa cells (IC50 = 3.3 μM). The three IR-780 derivatives displayed a photothermal response in a concentration-dependent manner, in which IR-780 AIEgens are more cytotoxic than IR-780, with IC50 of 0.3 μM under 808 nm laser irradiation. In tumor-bearing mice, the optimal probe IR780-O-TPE also showed a more effective photothermal response than IR-780. By illustrating the relationship between aggregation state with photophysical properties, cell imaging, and cytotoxicity, this work is helpful in modulating NIR-based photosensitizers into AIE features for efficient image-guided theranostics.

Recent Advances in Cyanine-Based Phototherapy Agents

“…Late apoptotic cell death increased when the cells were treated with the probes (0.6 μM, 24 h) upon 5-min irradiation. Furthermore, in 4T1 tumor-bearing mice, IR780-O-TPE was proved to have a more effective PTT response than IR780 itself, proposing an optimal photosensitizer ( Zhao et al, 2020 ).…”

A glutathione-activated carrier-free nanodrug of triptolide as a trackable drug delivery system for monitoring and improving tumor therapy

“…42,43 IR780 (Cy) is also one of the heptamethine cyanine probes that has been widely studied in the field of cancer theranostic. [44][45][46][47][48] However, very few reports have been provided about carrier-free nanodrugs based on heptamethine cyanine dyes. 49,50 In this study, we synthesized a structurally similar carrier-free nanodrug of triptolide (CyssTPN and CyccTPN).…”

Aggregation-Induced Fluorogens in Bio-Detection, Tumor Imaging, and Therapy: A Review

“…18 Occasionally, hijacking the ACQ to AIE have been realized for stable emission. 47 The red emissive fluorophores are converted from ACQ to AIE by conjugating with AIE molecules brings about AIE emission. Introducing the TPE with IR-780 core dye exhibits a typical D-A molecular structure favoring "off-on" fluorescence (7 and 8).…”

“…49,23 Because of low photon scattering and phototoxicity, negligible autofluorescence, 22,23,50 deep tissue penetration, the NIR and two-photon capable AIEgens enlightens the biomedical application effectively. 47,48,50,51 The NIR capable AIE molecules are constructed by improving the D-A-D effect by installing substituents with strong electron donors and acceptors to elevate the HOMO level and lower the LUMO level. 43 Furthermore, the quantum efficiency of the molecules are boosted by careful design strategies.…”