Near‐Infrared Fluorescent Heptamethine Cyanine Dyes for COX‐2 Targeted Photodynamic Cancer Therapy

Abstract

We designed and synthesized two heptamethine cyanine-based theranostic probes that aimed to target COX-2 in cancer cells. One is I-IR799-CXB, in which I-IR799 is conjugated to the COX-2-specific inhibitor, celecoxib, and another is I-IR799-IMC, where the non-selective COX inhibitor, indomethacin, was used. I-IR799 is a heptamethine cyanine derivative that can be activated by near-infrared light for photodynamic therapy (PDT) purposes. I-IR799-CXB and I-IR799-IMC were tested for their cancer-targeting capacity and photodynamic efficiency toward hepatocellular carcinoma (HepG2) cells relative to normal liver cells, alpha mouse liver 12 (AML12) cells. Interestingly, after conjugation, I-IR799-IMC exhibited better tumour targetability and PDT efficiency than I-IR799-CXB.

Single‐Component Dual‐Functional Autoboost Strategy by Dual Photodynamic and Cyclooxygenase‐2 Inhibition for Lung Cancer and Spinal Metastasis

“…Previous studies have reported that COX‐2 inhibitors have cancer targetability and direct anti‐inflammatory effects to enhance the antitumor capacity of PDT. [ 20 ] However, few studies focused on the synergistic effect of PDT and COX‐2 inhibitors on immune activation. Given the capacity for ICD induction and PGE 2 and IDO1 downregulation, we further determined T cell infiltration and activation after DHU‐CBA2 treatment with PDT.…”

Combination of PEG‐b‐PAA Carrier and Efficient Cationic Photosensitizers for Photodynamic Therapy

“…With the rapid development of PSs in recent years, PDT has been proven to be effective in the anti‐cancer treatment of head and neck cancer, skin cancer and early obstructive lung cancer [7] . As far as we know, some traditional fluorophores like tetrapyrrole cores, BODIPY dyes, [8] and cyanine derivatives [9] have been widely used to construct PSs for the ablation of cancer cells, and even a couple of tetrapyrrole‐based compounds have been approved as drugs for clinical PDT by several governments [10] . However, most of these PSs are hydrophobic and planar, which easily aggregate in the aqueous environment, leading to not only the notorious aggregation‐caused fluorescence quenching (ACQ) effect but also the decreasing photosensitizing efficiency [11] .…”

Role of Polymethinic Chain Substitution on the Two‐Photon Absorption Cross‐section of Heptamethine Cyanine Dyes

“…Cyanine dyes have electronic states that absorb and emit in the visible and in the infrared parts of the spectrum, they are commercially available and affordable, they are positively charged (which allows them to be used in aqueous media), their toxicities (or those of nanoparticles formed from them) are low enough to be biocompatible, they are functionalizable and most of them are chemically stable [17,37] . Determining the relationship between the structure of a dye and its TPA properties opens the path for cyanines to be used in frontier applications such as photopharmacology, photodynamic therapy, photothermal therapy and high‐resolution 3D imaging [27,38–42] . Certain variables, such as the length of the conjugated chain, have been explored to increase their TPA cross‐sections, but the role of the substitution of the carbons of the chains of equal length has not been systematically investigated.…”

“…[5] Cyanines are widely used in research and development because of their remarkable optical properties, namely their tunable absorption and emission of light. [17][18][19][20] Applications of these synthetic materials include their pioneering use as photosensitizers in photography, [21] and have seen renewed interest in recent years, [22][23][24][25] for example in their use as tissuespecific labeling, [26] as fluorescent probes, [27,28] as standards for IR quantum yield measurements, [29] as donor-acceptor pairs in microscopic distance measurements, [30] as photosensitizers in prodrugs for chemo-phototherapy, [31] as photo-caging groups activated by near-IR light, [32] as saturable absorbers, [33] in telecommunications [34] and in photoremovable protecting groups (PPG) [35] and also their surprising use in the preparation of Bose-Einstein condensates at room temperature. [36] Cyanine dyes have electronic states that absorb and emit in the visible and in the infrared parts of the spectrum, they are commercially available and affordable, they are positively charged (which allows them to be used in aqueous media), their toxicities (or those of nanoparticles formed from them) are low enough to be biocompatible, they are functionalizable and most of them are chemically stable.…”

“…[17,37] Determining the relationship between the structure of a dye and its TPA properties opens the path for cyanines to be used in frontier applications such as photopharmacology, photodynamic therapy, photothermal therapy and high-resolution 3D imaging. [27,[38][39][40][41][42] Certain variables, such as the length of the conjugated chain, have been explored to increase their TPA cross-sections, but the role of the substitution of the carbons of the chains of equal length has not been systematically investigated.…”