Mitochondria‐Targeted Two‐Photon Fluorescent Photosensitizers for Cancer Cell Apoptosis via Spatial Selectability

Abstract

Organelle‐targeted photosensitizers have been reported to be effective cell apoptosis agents. Mitochondria is recognized as an ideal target for cancer treatment due to its central role in oxidative metabolism and apoptosis. Meanwhile, two‐photon (TP) fluorescence microscopy has become a powerful tool for fluorescence imaging in biological events based on its minimizing photodamage/photobleaching and intrinsic 3D resolution in deep tissues and in vivo. In this study, a series of novel mitochondrial‐targeted TP fluorescent photosensitizers (TP‐tracers) are designed, synthesized, and systematically investigated. These TP‐tracers exhibit extraordinary anti‐interference capability among different cations, anions, and amino acids as well as the insensitivity to the changes of pH and complex biological environments. TP‐tracers are further used in fluorescence living cells, Drosophila brains, and zebrafish imaging with low cytotoxicity, excellent mitochondria‐targeting, and TP properties. The results demonstrate efficient mitochondria‐targeting cell selective apoptosis based on TP‐activated cancer cells with highly single cell selectivity, and the pharmacokinetic study reveals that MitoY2 does not have accumulation in rats. It is believed that these molecules hold great potential in TP‐related smart phototherapy.

Mito‐Bomb: Targeting Mitochondria for Cancer Therapy

“…Compared with guanidine and N + ions, the lipophilic cationic unit TPP has the most optimal mitochondria‐targeting ability. [ 40,381 ] Therefore, TPP is often adopted to build mitochondria‐targeting systems. However, lipophilic cation‐conjugated nanoparticles often take hours to escape from endosomes/lysosomes before targeting mitochondria, and the MTP may be degraded by proteases in endosomes/lysosomes.…”

Recent advances and prospects of carbon dots in cancer nanotheranostics

“…Two-photon FL imaging (TPFI), which commonly uses NIR femtosecond pulse lasers as light sources, has also received considerable attention in basic biological research and clinical diagnostics because of its large penetration depth, minimized tissue fluorescence imaging with advantages of autofluorescence background, and reduced photodamage in biotissues. [71][72][73][74] To date, various CDs have been widely constructed as two-photon reagents. In 2007, Sun et al first used surface-passivated CDs with a high two-photon absorption cross-section of 39000 Göppert-Mayer (GM) units for multiphoton imaging.…”

Optical properties of photodynamic therapy drugs in different environments: the paradigmatic case of temoporfin

“…16 PDT has proven efficient in the treatment of a variety of diseases, including psoriasis 17 as well as certain types of cancer, 18 such as esophageal 19 and cervical, 20 greatly limiting the side-effect of conventional therapy due to the spatial-selectivity of irradiation. 21,22 There are several requirements that should be met by PDT agents to increase their efficiency and guarantee their therapeutic effects. 23 These include: facile ISC, high quantum yield for the production of 1 O 2 , 24 absorption in the red or infrared portion of the electromagnetic spectrum to cover the therapeutic window for which penetration into tissues is maximal, 25 as well as enhanced selectivity towards bacterial 26 or cancer cells.…”