The low selectivity of currently available photosensitizers, which causes the treatment-related toxicity and side effects on adjacent normal tissues, is a major limitation for clinical photodynamic therapy (PDT) against cancer. Moreover, since PDT process is strongly oxygen dependent, its therapeutic effect is seriously hindered in hypoxic tumor cells. To overcome these problems, a cell-specific, H(2)O(2)-activatable, and O(2)-evolving PDT nanoparticle (HAOP NP) is developed for highly selective and efficient cancer treatment. The nanoparticle is composed of photosensitizer and catalase in the aqueous core, black hole quencher in the polymeric shell, and functionalized with a tumor targeting ligand c(RGDfK). Once HAOP NP is selectively taken up by α(v)β(3) integrin-rich tumor cells, the intracellular H(2)O(2) penetrates the shell into the core and is catalyzed by catalase to generate O(2), leading to the shell rupture and release of photosensitizer. Under irradiation, the released photosensitizer induces the formation of cytotoxic singlet oxygen ((1)O(2)) in the presence of O(2) to kill cancer cells. The cell-specific and H(2)O(2)-activatable generation of (1)O(2) selectively destroys cancer cells and prevents the damage to normal cells. More significantly, HAOP NP continuously generates O(2) in PDT process, which greatly improves the PDT efficacy in hypoxic tumor. Therefore, this work presents a new paradigm for H(2)O(2)-triggered PDT against cancer cells and provides a new avenue for overcoming hypoxia to achieve effective treatment of solid tumors.
Coordination chemistry plays an essential role in the design of photoluminescent probes for metal ions. Metal coordination to organic dyes induces distinct optical responses which signal the presence of metal species of interest. Luminescent lanthanide (Ln(3+)) and transition metal complexes of d(6), d(8) and d(10) configurations often exhibit unique luminescence properties different from organic dyes, such as high quantum yield, large Stokes shift, long emission wavelength and emission lifetimes, low sensitivity to microenvironments, and can be explored as lumophores to construct probes for metal ions, anions and neutral species. In this review, the design principles and coordination chemistry of metal probes based on mechanisms of PeT, PCT, ESIPT, FRET, and excimer formation will be discussed in detail. Particular attention will be given to rationales for the design of turn-on and ratiometric probes. Moreover, phosphorescent probe design based on Ln(3+) and d(6), d(8) and d(10)-metal complexes are also presented via discussing certain factors affecting the phosphorescence of these metal complexes. A survey of the latest progress in photoluminescent probes for identification of essential metal cations in the human body or toxic metal cations in the environment will be presented focusing on their design rationales and sensing behaviors. Metal complex-based photoluminescent probes for biorelated anions such as PPi, and neutral biomolecules ATP, NO, and H(2)S will be discussed also in the context of their metal coordination-related sensing behaviors and design approaches.
Quick: An exogenously induced quick increase of the H2S concentration (80 s) in MCF‐7 cells can be visualized by ratiometric imaging using a new probe (CouMC) that can target mitochondria. CouMC was constructed by combining merocyanine and coumarin fluorophores. The selective nucleophilic addition of HS− to the merocyanine derivative at neutral pH is crucial for the rapid H2S detection.
The UV- and sensor-induced interferences to living systems pose a barrier for in vivo Zn(2+) imaging. In this work, an intramolecular charge transfer (ICT) fluorophore of smaller aromatic plane, 4-amino-7-nitro-2,1,3-benzoxadiazole, was adopted to construct visible light excited fluorescent Zn(2+) sensor, NBD-TPEA. This sensor demonstrates a visible ICT absorption band, a large Stokes shift, and biocompatibility. It emits weakly (Phi = 0.003) without pH dependence at pH 7.1-10.1, and the lambda(ex) and lambda(em) are 469 (epsilon(469) = 2.1 x 10(4) M(-1) cm(-1)) and 550 nm, respectively. The NBD-TPEA displays distinct selective Zn(2+)-amplified fluorescence (Phi = 0.046, epsilon(469) = 1.4 x 10(4) M(-1) cm(-1)) with emission shift from 550 to 534 nm, which can be ascribed to the synergic Zn(2+) coordination by the outer bis(pyridin-2-ylmethyl)amine (BPA) and 4-amine. The Zn(2+) binding ratio of NBD-TPEA is 1:1. By comparison with its analogues NBD-BPA and NBD-PMA, which have no Zn(2+) affinity, the outer BPA in NBD-TPEA should be responsible for the Zn(2+)-induced photoinduced electron transfer blockage as well as for the enhanced Zn(2+) binding ability of 4-amine. Successful intracellular Zn(2+) imaging on living cells with NBD-TPEA staining exhibited a preferential accumulation at lysosome and Golgi with dual excitability at either 458 or 488 nm. The intact in vivo Zn(2+) fluorescence imaging on zebrafish embryo or larva stained with NBD-TPEA revealed two zygomorphic luminescent areas around its ventricle which could be related to the Zn(2+) storage for the zebrafish development. Moreover, high Zn(2+) concentration in the developing neuromasters of zebrafish can be visualized by confocal fluorescence imaging. This study demonstrates a novel strategy to construct visible light excited Zn(2+) fluorescent sensor based on ICT fluorophore other than xanthenone analogues. Current data show that NBD-TPEA staining can be a reliable approach for the intact in vivo Zn(2+) imaging of zebrafish larva as well as for the clarification of subcellular distribution of Zn(2+) in vitro.
Limited therapeutic efficacy to hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy(PDT). Tw on ew benzothiophenylisoquinoline (btiq)-derived cyclometalated Ir III complexes, IrL1 and MitoIrL2,w ere constructed as potent photosensitizers, with the latter being designed for mitochondria accumulation. Both complexes demonstrated at ype IP DT process and caused photoinduced ferroptosis in tumor cells under hypoxia. This ferroptosis featured lipid peroxide accumulation, mitochondria shrinkage,d own-regulation of glutathione peroxidase 4(GPX4), and ferrostatin-1 (Fer-1)-inhibited cell death. Upon photoirradiation under hypoxia, mitochondria targeting MitoIrL2 caused mitochondria membrane potential (MMP) collapse,A TP production suppression, and induced cell apoptosis.T he synergetic effect of ferroptosis and apoptosis causes MitoIrL2 to outperform IrL1 in inhibiting the growth of MCF-7, PANC-1, MDA-MB-231 cells and multicellular spheroids.T his study demonstrates the first example of ferroptosis induced by photosensitizing Ir III complexes.Moreover,t he synergism of ferroptosis and apoptosis provides ap romising approach for combating hypoxics olid tumors through type IP DT processes.
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