A Platinum(II) Complex of Heptamethine Cyanine for Photoenhanced Cytotoxicity and Cellular Imaging in Near‐IR Light

Abstract

Controlled generation of cytotoxic agents with near-IR light is a current focus of photoactivated cancer therapy, including that involving cytotoxic platinum species. A heptamethine cyanine scaffolded Pt complex, IR797-Platin exhibits unprecedented Pt-O bond scission and enhancement in DNA platination in near-IR light. This complex also displayed significant singlet oxygen quantum yield thereby qualifying as a near-IR photodynamic therapeutic agent. The complex showed 30-60 fold enhancement of cytotoxicity in near-IR light in various cancer cell lines. The cellular imaging properties were also leveraged to observe its significant co-localization in cytoplasmic organelles. This is the first demonstration of a near-IR light-initiated therapy involving the cytotoxic effects of both active cisplatin and singlet oxygen.

Diazido platinum(iv) complexes for photoactivated anticancer chemotherapy

“…curcumin) undergo ligand dissociation followed by solvent substitution. [45][46][47][48][49] • Photocleavage of ligand: Photon absorption by the metal centre can result in the cleavage of organic bonds, (e.g. C-N, N-O) in photosensitive o-nitrobenzyl alcohol derivatives coordinated to platinum.…”

Cyanine conjugates in cancer theranostics

“…Under photo-irradiation, the activated prodrug exhibited superior antitumor activity than the intact conjugate in MTT assay but was less potent than its parent drug. For more direct photocleavage, Mitra et al developed a platinum (II) prodrug by conjugating cisplatin with IR797 via a photodetachable O^O bidentate linkage ( 17 ) [ 37 ]. Upon NIR-triggered photoscission of Pt–O bond, an aquated (bioactive) form of cisplatin was released from the conjugate.…”

Photoactivation Strategies for Therapeutic Release in Nanodelivery Systems

“…Linker Oxidation and Reduction: Linker cleavage is induced indirectly through linker oxidation by reaction with 1 O 2 produced under the irradiation condition, [114,115,129,130,158] or reduction via photoelectron transfer. [118] This occurs in a cyanine class of linker, which shows an oxidative fragmentation by Vis-NIR irradiation (690 nm, 780 nm) as illustrated in Figure 4A.…”

“…[118] This occurs in a cyanine class of linker, which shows an oxidative fragmentation by Vis-NIR irradiation (690 nm, 780 nm) as illustrated in Figure 4A. [129,130,158] Of interest is its dual function by serving as PS itself that catalyzes 1 O 2 production, [129,130] and then participating in [2+2] cycloaddition with 1 O 2 that results in its dioxetane adducts. Due to their instability, these adducts rapidly undergo a series of self-fragmentations and cellular hydrolysis, leading to its payload release.…”