RESUMO
Although photodynamic therapy (PDT) has been extensively studied as an established modality of cancer treatment, it still suffers from a few clinical limitations, such as skin phototoxicity and tumor hypoxia. To circumvent these hurdles, hollow silica mesoporous nanoparticles (HMSNs) loaded with photosensitizers were employed as the nanoplatform to construct multifunctional nanoparticles (NPs). Specifically, an ultra-uniform polydopamine (PDA) shell was highly controlled grown around HMSNs by photogenerated outwards-diffused 1O2, followed by conjugation of folic acid-poly(ethylene glycol) and chelation of Fe2+ ions. Thanks to the optimal thickness of light-absorbing PDA shell, the multifunctional NPs exhibited not only negligible skin phototoxicity but also efficient 1O2 generation and photothermal (PT)-enhanced â¢OH generation upon respective photoirradiation. Anti-tumor therapy was then performed on both 4 T1 tumor cells and tumor-bearing mice by the combination of 638 nm PDT and 808 nm PT-enhanced chemodynamic therapy (CDT). As a result, high therapeutic efficacy was achieved compared to single-modality therapy, with a cell inhibitory rate of 86% and tumor growth inhibition of 70.4% respectively. More interestingly, tumor metastasis was effectively inhibited by the synergetic treatment. These results convincingly demonstrate that our multifunctional NPs are very promising skin-safe PDT agents combined with CDT for efficient tumor therapy.
Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Indóis/farmacologia , Indóis/uso terapêutico , Camundongos , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/uso terapêutico , Dióxido de Silício/uso terapêuticoRESUMO
A series of Ru(II)-containing metallopolymers with different polypyridyl complexes, namely [Ru(N^N)2(L)](PF6)2 (L = bipyridine-branched polymer; N^N = bpy: 2,2'-bipyridine (Ru 1); phen: 1,10-phenanthroline (Ru 2); dpp: 4,7-diphenyl-1,10-phenanthroline (Ru 3)), were synthesized with the motive that adjusting π-conjugation length of ligands might produce competent luminescent oxygen probes. The three hydrophobic metallopolymers were studied with 1H NMR, UV-Vis absorption, and emission spectroscopy, and then were utilized to prepare biocompatible nanoparticles (NPs) via a nanoprecipitation method. Luminescent properties of the NPs were investigated against dissolved oxygen by steady-state and time-resolved spectroscopy respectively. Luminescence quenching of the three NPs all followed a linear behavior in the range of 0-43 ppm (oxygen concentration), but Ru 3-NPs exhibited the highest oxygen sensitivity (82%) and longest emission wavelength (λex = 460 nm; λem = 617 nm). In addition, external interferons from cellular environments (e.g., pH, temperature, and proteins) had been studied on Ru 3-NPs. Finally, dissolved oxygen in monolayer cells under normoxic/hypoxic conditions was clearly differentiated by using Ru 3-NPs as the luminescent sensor, and, more importantly, hypoxia within multicellular tumor spheroids was vividly imaged. These results suggest that such Ru(II)-containing metallopolymers are strong candidates for luminescent nanosensors towards hypoxia. Graphical abstract.
Assuntos
Substâncias Luminescentes/química , Oxigênio/análise , Rutênio/química , Hipóxia Tumoral , 2,2'-Dipiridil/química , Células HeLa , Humanos , Ligantes , Luminescência , Medições Luminescentes/métodos , Fenantrolinas/químicaRESUMO
Photothermal therapy following microscopic temperature detection can avoid overheating effects or insufficient heating, and thus improve therapeutic efficacy. In this study, biocompatible dual-functional nanoparticles (NPs) are constructed from polypyrrole (PPy) and rhodamine B (RB) by a one-step modified polymerization method. The polypyrrole serves as a photothemal agent, and rhodamine B acts as a temperature-sensing probe. The polypyrrole-rhodamine B (PPy-RB) NPs possess a high photothermal effect on irradiation by 808 nm laser, and a competent temperature sensitivity for the real-time temperature monitoring based on the emission intensity response of rhodamine B. After acting on HepG2 cells, the PPy-RB NPs can effectively induce cancer cell death, and the microscopic temperature is monitored by fluorescence feedback from rhodamine B during PTT by laser confocal microscopy. Hence, the proposed approach can supply a facile and promising way for the fabrication of effective theranostic nanoplatforms assisted by self-monitoring of cancer therapeutic processes.
Assuntos
Nanopartículas/química , Terapia Fototérmica , Polímeros/farmacologia , Pirróis/farmacologia , Rodaminas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Teste de Materiais , Tamanho da Partícula , Polímeros/química , Pirróis/química , Rodaminas/química , Propriedades de Superfície , Temperatura , Células Tumorais CultivadasRESUMO
In this study, fluorescence-encoded magnetic biocompatible nanoparticles (NPs) were constructed from CdSe@ZnS quantum dots (QDs) and Fe3O4 nanoparticles with a one-step reprecipitation-encapsulation method. The resultant hybrid NPs exhibit small size (â¼130 nm in diameter), highly bright QDs, two-color emissions (green and red) under single-wavelength excitation, easy separation with a magnet and efficient cellular internalization. Energy transfer between the incorporated QDs was studied to better tailor the encoded fluorescence, and 11 barcodes were obtained by adjusting the ratio of green and red QDs. We used four sets of the barcodes to tag specific cancer cells (HepG2) as a proof-of-concept, and distinguished each set according to respective overlayed fluorescence images using laser confocal microscopy. Moreover, the incorporated Fe3O4 NPs endowed as-constructed optical barcode superparamagnetic property by T 2-enhanced magnetic resonance effect with an r 2 value of 145.25 s-1 mM-1 at 3 T. These results suggest that the multifunctional NPs are very promising for discriminating different cells and dual-modality imaging.
RESUMO
Conjugated polymer hybrid nanoparticles (NPs) loaded with both indocyanine green (ICG) and 1,3-diphenylisobenzofuran (DPBF) are described. The NPs are dually functional in that ICG acts as the photosensitizer, and DPBF as a probe for singlet oxygen (1O2 probe). The nanoparticle core consists of the energy donating host poly(9,9-dioctylfluorenyl-2,7-diyl)-co-(2,5-p-xylene) (PFP). The polymer is doped with the energy acceptor DPBF. Ratiometric fluorometric detection of singlet oxygen is accomplished by measurement of fluorescence at wavelengths of 415 and 458 nm. In addition, the shell of the positively charged polymeric nanoparticles was modified, via electrostatic interaction, with negatively charged PDT drugs ICG. The integrated nanoparticles of type ICG-DPBF-PFP display effective photodynamic performance under 808-nm laser irradiation. The 1O2 sensing behaviors of samples are evaluated based on the ratiometric fluorescent responses produced by DPBF and PFP. 1O2 can be fluorimetically sensed with a detection limit of 28 µM. The multifunctional nanoprobes exhibit effortless cellular uptake, superior photodynamic activity and a rapid ratiometric response to 1O2. Graphical abstractSchematic of a dual-functional nanoplatform for photodynamic therapy (PDT) and singlet oxygen (1O2) feedback. It offers a new strategy for self-monitoring photodynamic ablation. FRET: fluorescence resonance energy transfer. Indocyanine green is attached in the shell of nanoparticles, and 1,3-diphenylisobenzofuran is doped into the energy donating host conjugated polymer.
Assuntos
Benzofuranos/química , Verde de Indocianina/química , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Polilisina/química , Oxigênio Singlete/análise , Benzofuranos/toxicidade , Transferência Ressonante de Energia de Fluorescência , Células Hep G2 , Humanos , Verde de Indocianina/efeitos da radiação , Verde de Indocianina/toxicidade , Raios Infravermelhos , Limite de Detecção , Nanopartículas/toxicidade , Fotoquimioterapia , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Polilisina/toxicidade , Oxigênio Singlete/químicaRESUMO
A collection of luminescent metal complexes have been widely used as oxygen probes in the biomedical field. However, single intensity-based detection approach usually suffered from errors caused by the signal heterogeneity or fluctuation of the optoelectronic system. In this work, respective ruthenium (II) and terbium (III) complexes were chosen to coordinate a bipyridine-branched copolymer, so that to produce oxygen-sensitive metallopolymer (Ru-Poly) and oxygen-insensitive metallopolymer (Tb-Poly). Based on the hydrophobic Ru-Poly and Tb-Poly, a ratiometric luminescent oxygen nanoprobe was facilely prepared by a nanoprecipitation method. The nanoprobes have a typical size of ~100 nm in aqueous solution, exhibiting a green-red dual-wavelength emission under the excitation of 300 nm and 460 nm, respectively. The red emission is strongly quenched by dissolved oxygen while the green one is rather stable, and the ratiometric luminescence was well fitted by a linear Stern-Volmer equation. Using the ratiometric biocompatible nanoprobes, the distribution of intracellular oxygen within three-dimensional multi-cellular tumor spheroids was successfully imaged.
RESUMO
Tumor hypoxia severely reduces the efficiency of photodynamic therapy (PDT) through the insufficient supply of oxygen. In this work, we reported on a design of fluorinated nanophotosensitizers (NPSs) prepared by a facile reprecipitation-encapsulation method, with the aim of addressing the issue of hypoxia. The fluorinated NPSs consisted of a hybrid particle core of perfluorosiloxane-polystyrene, doped with a fluorinated photosensitizer, and a biocompatible poly-l-lysine shell. Compared with non-fluorinated counterpart NPSs that are similarly prepared except for the replacement of perfluorosiloxane with alkoxysilane, the fluorinated NPSs saturated with O2 exhibit approximately 3.5 fold higher singlet oxygen production yield and higher in vitro PDT efficiency due to the O2-carrying capability of intra-particle 'F-C' bonds.
Assuntos
Nanopartículas/química , Fármacos Fotossensibilizantes/química , Hipóxia Celular , Sobrevivência Celular/efeitos dos fármacos , Fluoretação , Células HeLa , Humanos , Lasers , Neoplasias/tratamento farmacológico , Oxigênio/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Polilisina/química , Poliestirenos/química , Oxigênio Singlete/química , Oxigênio Singlete/metabolismoRESUMO
Metal complex-based luminescent oxygen nanosensors have been intensively studied for biomedical applications. In terms of monitoring dynamics of intracellular oxygen, however, high-quality nanosensors are still badly needed, because of stringent requirements on stability, biocompatibility and luminescence intensity, aside from oxygen sensitivity. In this paper, we reported a type of highly luminescent and stable oxygen nanosensors prepared from metallopolymer. First, a novel ruthenium(II)-containing metallopolymer was synthesized by chelating the oxygen probe [Ru(bpy)3]2+ with a bipyridine-branched hydrophobic copolymer, which was then doped into polymeric nanoparticles (NPs) by a reprecipitation method, followed by further conjugation to selectively target mitochondria (Mito-NPs). The resultant Mtio-NPs possessed a small hydrodynamic size of â¼85 nm, good biocompatibility and high stability resulting from PEGylation and stable nature of Ru-complex. Because the complexed [Ru(bpy)3]2+ homogeneously resided on particle surface, Mito-NPs exhibited strong luminescence at 608 nm that was free of aggregation-caused-quenching, the utmost oxygen sensitivity of free [Ru(bpy)3]2+ probe ( Q = 75%), and linear Stern-Volmer oxygen luminescence quenching plots. Taking advantage of the mitochondria-specific nanosensors, intracellular oxygenation and deoxygenation processes were real-time monitored for 10 min by confocal luminescence imaging, visualized by the gradual weakening (by more than 90%) and enhancing (by 50%) of the red emission, respectively.
Assuntos
Resinas Acrílicas/química , Substâncias Luminescentes/química , Mitocôndrias/metabolismo , Nanopartículas/química , Oxigênio/análise , Poliestirenos/química , Resinas Acrílicas/síntese química , Resinas Acrílicas/toxicidade , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Células Hep G2 , Humanos , Luminescência , Substâncias Luminescentes/síntese química , Substâncias Luminescentes/toxicidade , Medições Luminescentes/métodos , Microscopia Confocal/métodos , Nanopartículas/toxicidade , Poliestirenos/síntese química , Poliestirenos/toxicidade , Estudo de Prova de Conceito , Rutênio/química , Rutênio/toxicidadeRESUMO
Encapsulation of luminescent perovskite quantum dots (QDs) into a solid matrix has been approved to be an efficient way to improve their stability. In this work, we reported a green encapsulation method to produce ultrastable CH3NH3PbBr3 QDs incorporated into the SiO2 matrix. Specifically, fresh-prepared CH3NH3PbBr3 QDs were covalently embedded into silica by an aqueous sol-gel method assisted with CH3NH3Br, which not only effectively inhibited the water-driven degradation of QDs through surface coordination, but also strongly stabilized the QDs in solid powder via concentration gradient. As far as we know, this silica encapsulation of perovskite QDs in aqueous environments is reported for the first time. Luminescent properties of perovskite QDs during the course of gelation as well as in resulting composite powder were investigated using steady-state and time-resolved spectroscopies, and a 2 wt % QD-doped sample treated with 11.5 mM of CH3NH3Br was demonstrated to be the optimal phosphor. The green-emissive phosphor had a PLQY of 60.3% and a full width at half maxima of â¼25 nm, exhibiting ultrahigh stability tested by cycle heating (120 °C), continuous heating (80 °C, 60 h), and light irradiation (450 nm light, 350 h). The phosphor was readily blended with polymers and applied as a color-converting layer on blue light-emitting diodes.
RESUMO
Ratiometric fluorescent nanoparticles (NPs) under two-photon excitation are successfully developed for sensing dissolved oxygen. The NPs comprise the oxygen probe Pt(II)-porphyrins (PtTFPP) and fluorescent organic semiconducting polymer (PFO). PFO polymer acts as both a two-photon antenna and a reference dye, while PtTFPP absorbs the photonic energy transferred by the PFO under two-photon excitation at 740 nm to sense oxygen. The red fluorescence of PtTFPP is sensitive to oxygen with a quenching response of 88% from nitrogen saturation to oxygen saturation, and PFO gives oxygen-insensitive referenced blue fluorescence. The fluorescence quenching of the NPs against oxygen at two-photon excitation follows a linear Stern-Volmer behavior. The nanosensors exhibit low cytotoxic effects as well as effortless cellular uptake. When incorporated into cells, the ratio of the signals increases up to about 500% from oxygen-saturated to oxygen-free environment.
Assuntos
Nanopartículas/química , Platina/química , Polímeros/química , Porfirinas/química , HumanosRESUMO
Sensing of intracellular singlet oxygen (1O2) is required in order to optimize photodynamic therapy (PDT). An optical nanoprobe is reported here for the optical determination of intracellular 1O2. The probe consists of a porous particle core doped with the commercial 1O2 probe 1,3-diphenylisobenzofuran (DPBF) and a layer of poly-L-lysine. The nanoparticle probes have a particle size of ~80 nm in diameter, exhibit good biocompatibility, improved photostability and high sensitivity for 1O2 in both absorbance (peak at 420 nm) and fluorescence (with excitation/emission peaks at 405/458 nm). Nanoprobes doped with 20% of DPBF are best suited even though they suffer from concentration quenching of fluorescence. In comparison with the commercial fluorescent 1O2 probe SOSG, 20%-doped DPBF-NPs (aged) shows higher sensitivity for 1O2 generated at an early stage. The best nanoprobes were used to real-time monitor the PDT-triggered generation of 1O2 inside live cells, and the generation rate is found to depend on the supply of intracellular oxygen. Graphical abstract A fluorescent nanoprobe featured with refined selectivity and improved sensitivity towards 1O2 was prepared from the absorption-based probe DBPF and used to real-time monitoring of the generation of intracellular 1O2 produced during PDT.
Assuntos
Benzofuranos/química , Corantes Fluorescentes/química , Oxigênio Singlete/metabolismo , Benzofuranos/efeitos da radiação , Benzofuranos/toxicidade , Fluorescência , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Células Hep G2 , Humanos , Luz , Nanopartículas/química , Nanopartículas/efeitos da radiação , Nanopartículas/toxicidade , Fotoquimioterapia , Polilisina/química , Polilisina/toxicidade , Oxigênio Singlete/análise , Oxigênio Singlete/química , Espectrometria de Fluorescência/métodosRESUMO
Luminescent perovskite quantum dots (QDs) had attracted great attention by virtue of the merits of color-tunable and narrow-band emissions. However, sofar reported perovskite QDs suffered from instability more or less. In this work, a type of silica-coated orthorhombic CH3NH3PbBr3 QDs (SiO2-QDs) with greatly improved stability was reported. The SiO2-QDs were one-pot synthesized using a reprecipitation-encapsulation method assisted with an amine functional silane, which not conly controlled the crystallization of QDs, but also encapsulated QDs with a silica layer simultaneously. More interestingly, the in situ encapsulation of silica shell induced the presence of orthorhombic perovskite that was thought to be unstable at room temperature. This is the first report of orthorhombic CH3NH3PbBr3 QDs, as far as we are concerned. The orthorhombic SiO2-QDs exhibited narrow-band green luminescence with a quantum yield of 78%, and a high production yield of â¼70wt%. Moreover, stability of SiO2-QDs was considerably improved due to silica-coating. White-LEDs were also successfully fabricated with the green SiO2-QDs and a red commercial phosphors using a noncontact configuration. These results demonstrated that the orthorhombic SiO2-QDs held great promise for high-performance display or lighting technology.
RESUMO
Multiplexed optical encoding is emerging as a powerful technique for high-throughput cellular analysis and molecular assays. Most of the developed optical barcodes, however, either suffer from large particle size or are incompatible with most commercial optical instruments. Here, a new type of nanoscale fluorescent barcode (Pdot barcodes) was prepared from semiconducting polymers. The Pdot barcodes possess the merits of small size (â¼20 nm in diameter), narrow emission bands (full-width-at-half-maximum (fwhm) of 30-40 nm), three-color emissions (blue, green, and red) under single-wavelength excitation, a high brightness, good pH and thermal stability, and efficient cellular uptake. The Pdot barcodes were prepared using a three-color and six-intensity encoding strategy; for ratiometric readout of the barcodes, one of the colors might be used as an internal reference. We used the Pdot barcodes to label 20 sets of cancer cells and then distinguished and identified each set based on the Pdot barcodes using flow cytometry. We also monitored and tracked single cells labeled with different Pdot barcodes, even through rounds of cell division. These results suggest Pdot barcodes are strong candidates for discriminating different labeled cell and for long-term cell tracking.
Assuntos
Corantes Fluorescentes/química , Polímeros/química , Pontos Quânticos/química , Análise de Célula Única , Compostos de Boro/química , Cor , Fluorenos/química , Corantes Fluorescentes/síntese química , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Estrutura Molecular , Fenômenos Ópticos , Tamanho da Partícula , Polímeros/síntese química , Semicondutores , Propriedades de Superfície , Temperatura , Células Tumorais CultivadasRESUMO
A type of polymeric nanoparticles loading indocyanine green and Pt(ii)-porphyrins (ICG-Pt-NPs) is constructed to achieve a synergistic effect of combined photothermal and two-photon activated photodynamic therapy. The nanoparticle core comprises the photosensitizer Pt(ii)-porphyrins (PtTFPP), and organic semiconducting polymer (PFO) that acts as a two-photon antenna. Negative ICG molecules, an NIR-absorbing photothermal dye, can be loaded into the positively charged poly-l-lysine (PLL) shell of the polymeric nanoparticles via electrostatic interaction. In these carefully designed ICG-PtTFPP integrated nanoparticles, PtTFPP absorbs the photonic energy transferred by the PFO polymer under two-photon laser excitation at 740 nm to induce photodynamic cancer cell death, while ICG offers nanoparticles a strong photothermal performance under 808 nm laser irradiation. Compared with photodynamic therapy or photothermal therapy alone, the combined therapy had a significantly synergistic effect and improved the therapeutic efficacy with near-infrared irradiation.
RESUMO
In this work luminescent nanosensors specifically created for intracellular oxygen (ic-O2) were utilized to assess photodynamic therapy (PDT) -induced cell damages. Firstly, ic-O2 was demonstrated to be consumed much faster than extracellular O2 with respective O2 nanosensors. Using the ic-O2 nanosensors, PDT-treated cells with different degree of impairment were then resolved according to the oxygen consumption rate (OCR). The evolving trend of cytotoxicity derived from OCRs was in agreement with cell viability obtained from 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Moreover, the direct damage of PDT on cell mitochondria was successfully detected by monitoring respiration instantly after PDT treatment, which is actually beyond the scope of MTT assay. These results suggest that fluorescence sensing of ic-O2-associated cell respiration is promising and even may become a standardized method, complementary to MTT assay, to evaluate PDT-induced cytotoxicity.
Assuntos
Oxigênio/análise , Apoptose , Linhagem Celular Tumoral , Respiração Celular , Sobrevivência Celular , Humanos , Consumo de Oxigênio , Fotoquimioterapia , Fármacos Fotossensibilizantes , Oxigênio SingleteRESUMO
Zinc(ii) phthalocyanine (ZnPc) is a promising photosensitizer for PDT but suffers from aggregation in a physiological aqueous environment. In this paper, a class of biocompatible polymeric nanoparticles (NPs) was prepared to encapsulate ZnPc molecules. Mostly because of the planar structure, ZnPc molecules were difficult to be encapsulated into the polymeric NPs unless further coated with a thick poly-l-lysine (PLL) layer. The PLL shell endowed the NPs with good biocompatibility, efficient cellular uptake, and potential bioconjugation. The degree of aggregation (DOA) of ZnPc molecules in PLL-NPs was thoroughly investigated based on self-defined relative DOA, and a loading capacity of 4 wt% was deduced as the turning point for aggravating aggregation. Similarly, the optimal loading capacity of ZnPc was determined to be 4% according to the 1O2 generation rate, demonstrating the feasibility of the DOA approach. Polymers with large rigid units (PVK and PFO) were also utilized to relieve the aggregation of ZnPc in NPs. Taking advantage of the optimized ZnPc-loaded NPs, high PDT efficacy was demonstrated in HepG2 cells and in tumor-bearing mice as well. Both high in vitro and in vivo PDT efficacy and biocompatibility are demonstrated. Aside from affording a class of efficient biocompatible nanophotosensitizers, this work is also instructive to design other types of ZnPc-based nanocarriers, in which aggregation should be well considered.
RESUMO
For most fluorescent oxygen sensors developed today, their fabrication process is either time-consuming or needs specialized knowledge. In this work, a robust fluorescent oxygen sensor is facilely constructed by dissolving pyrene molecules into CTAB aqueous solution. The as-prepared pyrene@micelle sensors have submicron-sized diameter, and the concentration of utilized pyrene can be reduced as low as 0.8 mM but still can exhibit dominant excimer emission. The excimer fluorescence is sensitive to dissolved oxygen in both intensity and lifetime, and the respective Stern-Volmer plot follows a nonlinear behavior justified by a two-site model. Because of the merits of large Stokes shift (~140 nm), easy fabrication, and robustness, the pyrene@micelle sensors are very attractive for practical determination of oxygen.
Assuntos
Técnicas Biossensoriais/métodos , Oxigênio/isolamento & purificação , Espectrometria de Fluorescência/métodos , Fluorescência , Humanos , Micelas , Pirenos/químicaRESUMO
Soft fluorescent nanomaterials have attracted recent attention as imaging agents for biological applications, because they provide the advantages of good biocompatibility, high brightness, and easy biofunctionalization. Here, we provide a survey of recent developments in fluorescent soft nano-sized biological imaging agents. Various soft fluorescent nanoparticles (NPs) (including dye-doped polymer NPs, semiconducting polymer NPs, small-molecule organic NPs, nanogels, micelles, vesicles, and biomaterial-based NPs) are summarized from the perspectives of preparation methods, structure, optical properties, and surface functionalization. Based on both optical and functional properties of the nano-sized imaging agents, their applications are then reviewed in terms of in vitro imaging, in vivo imaging, and cellular-process imaging, by means of specific or nonspecific targeting.
Assuntos
Corantes Fluorescentes , Nanoestruturas , Imagem Óptica , Espectroscopia de Luz Próxima ao Infravermelho , Animais , Linhagem Celular , Feminino , Humanos , Camundongos , Camundongos Nus , Tamanho da PartículaRESUMO
Cellular respiration is a worthwhile criterion to evaluate mitochondrial dysfunction by measuring the dissolved oxygen. However, most of the existing sensing strategies merely report extracellular (ec-) or intracellular (ic-) O2 rather than intramitochondrial (im-) O2 . Herein we present a method to assess tumor mitochondrial dysfunction with three phosphorescent nanosensors, which respond to ec-, ic-, and im-O2 . Time-resolved luminescence is applied to determine the respective oxygen consumption rates (OCRs) under varying respiratory conditions. Data obtained for the OCRs and on (intra)cellular O2 gradients demonstrate that mitochondria in tumor cells are distinctly less active than those of healthy cells, resulting from restrained glucose utilization of and physical injury to the mitochondria. We believe that such a site-resolved sensing strategy can be applied to numerous other situations, for example to evaluate the adverse effects of drug candidates.