RESUMO
Chemoresistance is one of the major challenges for cancer treatment, more recently ascribed to defective mitochondrial outer membrane permeabilization (MOMP), significantly diminishing chemotherapeutic agent-induced apoptosis. A boron-dipyrromethene (BODIPY) chromophore-based triarylsulfonium photoacid generator (BD-PAG) was used to target mitochondria with the aim to regulate mitochondrial pH and further depolarize the mitochondrial membrane. Cell viability assays demonstrated the relative biocompatibility of BD-PAG in the dark while live cell imaging suggested high accumulation in mitochondria. Specific assays indicated that BD-PAG is capable of regulating mitochondrial pH with significant effects on mitochondrial membrane depolarization. Therapeutic tests using chlorambucil in combination with BD-PAG revealed a new strategy in chemoresistance suppression.
Assuntos
Antineoplásicos , Mitocôndrias , Neoplasias , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Neoplasias/tratamento farmacológicoRESUMO
The nature of linear photophysical and nonlinear optical properties of a new squaraine derivative 2,4-bis[4-(azetidyl)-2-hydroxyphenyl]squaraine (1) with efficient near-infrared (NIR) emission was comprehensively analyzed based on spectroscopic, photochemical, and two-photon absorption (2PA) measurements, along with quantum chemical analysis. The steady-state absorption, fluorescence, and excitation anisotropy spectra of 1 and its fluorescence emission lifetimes revealed the multiple aspects of the electronic structure of 1, including the relative orientations of the main transition dipoles, effective rotational volumes in solvents of different polarities, and a maximum molar extinction of 1.35 × 10-5 M-1·cm-1, which is unusually small for similar symmetric squaraines. The degenerate 2PA spectrum of 1 was obtained over a broad spectral range under femtosecond excitation, using standard open-aperture Z-scan and two-photon induced fluorescence methods, revealing maximum 2PA cross sections of â¼400 GM. Squaraine 1 exhibited efficient superluminescence emission in the polar solvent (dichloromethane) at room temperature under femtosecond pumping conditions. Quantum chemical analysis of the electronic structure of 1 was performed using the DFT/TD-DFT level of theory and found to be in good agreement with experimental data. The new squaraine derivative 1 displayed high fluorescence quantum yield, efficient NIR superluminescence, large 2PA cross sections, and high photostability with a photodecomposition quantum yield â¼4 × 10-6, suggesting its potential for applications in two-photon fluorescent bioimaging and lasing.
Assuntos
Ciclobutanos , Corantes Fluorescentes , Ciclobutanos/química , Corantes Fluorescentes/química , Fenóis/química , Fótons , Solventes/químicaRESUMO
Fluorescent organic nanoparticles (FONs) are emerging as an attractive alternative to the well-established fluorescent inorganic nanoparticles or small organic dyes. Their proper design allows one to obtain biocompatible probes with superior brightness and high photostability, although usually affected by low colloidal stability. Herein, we present a type of FONs with outstanding photophysical and physicochemical properties in-line with the stringent requirements for biomedical applications. These FONs are based on quatsome (QS) nanovesicles containing a pair of fluorescent carbocyanine molecules that give rise to Förster resonance energy transfer (FRET). Structural homogeneity, high brightness, photostability, and high FRET efficiency make these FONs a promising class of optical bioprobes. Loaded QSs have been used for in vitro bioimaging, demonstrating the nanovesicle membrane integrity after cell internalization, and the possibility to monitor the intracellular vesicle fate. Taken together, the proposed QSs loaded with a FRET pair constitute a promising platform for bioimaging and theranostics.