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The development of anticancer therapy is significant to human health but remains a huge challenge. Photodynamic therapy (PDT), inducing the synergistic mitochondrial dysfunction in cancer cells is a promising approach but suffer from the low efficiency in hypoxic microenvironment and deep‐seated tumors. Herein, to improve the outcomes of PDT for cancer treatment, a series of red fluorophores consisting of dual‐cationic triphenylphosphonium‐alkylated pyridinium and (substituted) triphenylamine are prepared as organelle‐targeting antitumor photosensitizers (PSs) with aggregation‐induced emission characteristics. These PSs can selectively accumulate at the mitochondria or lysosomes of cancer cells with both dark‐ and photo‐cytotoxicity, making them possess excellent killing effect on cancer cells and efficient inhibition of tumor growth in living mice. This study brings about new insight into the development of powerful cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract A subcellular organelle-targeted delivery of anti-cancer drugs is a promising strategy to maximize the anti-cancer effects and minimize the adverse effects. Herein, we prepared a mitochondria-targeted drug delivery nanoplatform based on IR780 iodide (IR780) and titanium disulfide (TiS2) nanosheets. Due to the large specific surface area of TiS2 nanosheets, the nanoplatform could highly load anti-cancer drug resveratrol (RV). The as-prepared nanocomposite (IR780-TiS2/RV) was used for an efficacious photothermal-triggered tumor chemotherapy. IR780-TiS2/RV showed satisfactory stability and biocompatibility, and the loading ratio of RV and IR780 was about 112% and 56%, respectively. Upon the near-infrared (NIR) irradiation, the heat generated by IR780-TiS2/RV could trigger the RV release. Due to the conjugation with the mitochondria-specific IR780, IR780-TiS2/RV could target and accumulate in mitochondria and release RV when triggered by NIR to decrease the mitochondrial membrane potential, rapidly induce the upregulation of key intrinsic apoptotic factors such as cytochrome c, and initiate the caspase cascade, thereby achieving the chemotherapeutic effect. The IR780-TiS2/RV nanocomposite was demonstrated to have a high anti-tumor efficacy in vitro and in vivo as well as no remarkable tissue toxicity. We believe our study demonstrates that the NIR-triggered IR780-TiS2/RV nanoplatform could be a promising chemotherapeutic agent in clinical practice.

Graphical abstract Highlights • Cy-OAcr is a mitochondria-targeting ratiometric near-infrared fluorescent probe. • The mechanism of probe via an unique adduct/intramolecular cyclization. • Cy-OAcr can selectively discriminate cysteine over other biothiols in cells. • Cy-OAcr can be used to imaging of cysteine in orthotopic lung cancer mice. Abstract Cysteine (Cys) plays significant roles in many physiological processes, although its normal concentration is maintained at the micromole level. Abnormally high levels of intracellular Cys can lead to many diseases including cancer. Recent years, many effective fluorescent probes have been developed for the selective detection of Cys against other biological thiols. Herein, we synthesized a ratiometric near-infrared (NIR) fluorescent probe Cy-OAcr for selective imaging of intracellular Cys. Cy-OAcr has a lipophilic iminium cation unit as the mitochondrial guider and an acrylate group as the Cys recognition unit as well as a fluorescence modulator for rearranging the conjugated π-electron system of cyanine fluorophore. Upon detection of Cys, there occurs a significant absorption and fluorescence spectral shift, which are desirably beneficial for ratiometric detection. This probe has high sensitivity and selectivity for Cys detection over glutathione (GSH), homocysteine (Hcy), and other biomolecules with a low limit of detection at 0.09 μM. Probe Cy-OAcr is capable to detect and image Cys in three living cancer cell lines and their corresponding tumor-bearing mice models. More importantly, we successfully apply this fluorescent probe to evaluate the level of Cys in orthotopic lung cancer model. Imaging analyses reveal that the probe can discriminate tumor lesions from normal tissues, indicating its significant potential applications for clinical auxiliary diagnosis of cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new leaving group diphenylborinate identified as pyruvate recognizing moiety. • An unusual Lewis acid base pair utilized for the detection of pyruvate. • The sensing strategy was witnessed by 1H NMR, HR-MS and DFT analysis. • The LOD of 16 nM of pyruvate with 1000-fold selectivity was obtained. • Mitotracking, exogenous, endogenous detection was tested with live Hela cells. Developing new reaction based recognizing units can enhance the specificity of target analyte molecules in practical applications of real samples and biosystems. Therefore, introducing a recognizing moiety diphenylborinate was encountered for the detection of pyruvate biomolecule through Lewis acid-base reaction based sensing strategy. The construction of the Schiff-base back bone between quinoline and N-(diethylamino)salicylaldehyde-diphenylborinate (QSB) were expressed the red shift from blue emission of quinoline in to green as that of dative bond developed between Schiff base nitrogen and boron atoms. The new sensing approach was involved such a way that fluorophore QSB is a Lewis acid while pyruvate acts as Lewis base, where the elimination of Lewis pair produced a weak green fluorescence including the formation of quinoline, N-(diethylamino)salicylaldehyde (QS). The switching products were witnessed through 1H NMR titration, HR-MS and FT-IR studies. The good selectivity and interference ability were achieved in presence of 1000-fold excess of possible interferences with LOD of 16 nM. Moreover, the tracking ability of the probe was employed towards pyruvate in live HeLa cell imaging for evaluating an exogenous and endogenous signals producing ability and its mitochondria targeting property was investigated successfully. Further, the practical utility of the probe was tested with milk samples and obtained good recovery results. [ABSTRACT FROM AUTHOR]

• Based 'successive' nucleophilic substitution high selective H 2 S detection was realized. • The probe can target mitochondrial-H 2 S with red light emissive fluorescent. • The probe successfully was applied imaging in living HeLa cells and mice. The research of endogenous hydrogen sulfide (H 2 S) biology function, pathological and pharmacological effects has been active in the field of chemists and biologists in recent years. Especially, consequent H 2 S detection mechanisms and biological applications based on fluorescence probe emerged in endlessly, competing ideas, each had its advantage. In facts, the reaction mechanism and luminescence properties play a decisive role in the biology application of H 2 S fluorescence probe. In this despite booming season, in the process of research we still skillfully conceived, in view of H 2 S with small structure being able to do successive nucleophilic substitution in the same molecules, high selective H 2 S subcellular detection was realized. Specifically, we take the cyanine (Cy7) with positive charge as a red fluorophore, through the introduction of disulfide bond and carbonate to build the specific reaction sites of H 2 S, thus avoiding the interference of other sulfur-containing substances in biological systems. After reaction with H 2 S, the Probe released red fluorophore, realizing mitochondria target H 2 S detection. Because the advantages of red fluorescence emission probe, the Probe successfully was applied imaging in mice. [ABSTRACT FROM AUTHOR]