RESUMO
Synergistic therapy has become the major therapeutic method for malignant tumors in clinical. Photodynamic therapy (PDT) and radiotherapy (RT) always combine together because of their identical anti-tumor mechanisms, that is reactive oxygen species are generated by the use of radiosensitizers after irradiation by X-ray to efficiently kill cancer cells, PDT also follows similar mechanism. Full exposure of energy-absorbing species in nanomaterials to X-ray or near-infrared light irradiation makes the energy interchange between nanomaterials and surrounding H2O or dissolved oxygen easier, however, it remains challenging. Herein, an ultrathin two-dimensional (2D) nanosheet (NS) is developed, Bi2O2CO3, doped with lanthanide ions to give out upconversion luminescence, where the high Z elements Bi, Yb, and Er promote the radio-sensitizing effect. To the surprise, lanthanide activator ions gave out completely different luminescence properties compared with traditional upconversion nanoparticles. Less dopant of Er ions in nanosheets lattice resulted in brighter red emission, which provides more efficient PDT. Under RT/PDT combined treatment, NS shows a good tumor growth-inhibiting effect. In addition, synergistic therapy requires lower radiation dose than conventional radiotherapy and lower light power than single photodynamic therapy, thus greatly reducing radiation damage caused by RT and thermal damage caused by PDT.
RESUMO
Optogenetic, known as the method of 21 centuries, combines optic and genetic engineering to precisely control photosensitive proteins for manipulation of a broad range of cellular functions, such as flux of ions, protein oligomerization and dissociation, cellular intercommunication, and so on. In this technique, light is conventionally delivered to targeted cells through optical fibers or micro light-emitting diodes, always suffering from high invasiveness, wide-field illumination facula, strong absorption, and scattering by nontargeted endogenous substance. Light-transducing nanomaterials with advantages of high spatiotemporal resolution, abundant wireless-excitation manners, and easy functionalization for recognition of specific cells, recently have been widely explored in the field of optogenetics; however, there remain a few challenges to restrain its clinical applications. This review summarized recent progress on light-responsive genetically encoded proteins and the myriad of activation strategies by use of light-transducing nanomaterials and their disease-treatment applications, which is expected for sparking helpful thought to push forward its preclinical and translational uses.
Assuntos
Optogenética , Optogenética/métodos , Humanos , Nanoestruturas/química , Animais , Nanotecnologia , NanomedicinaRESUMO
Nanomaterials doped with high atom number elements can improve the efficacy of cancer radiotherapy, but their clinical application faces obstacles, such as being difficult to degrade in vivo, or still requiring relatively high radiation dose. In this work, a bismuth oxycarbonate-based ultrathin nanosheet with the thickness of 2.8 nm for safe and efficient tumor radiotherapy under low dose of X-ray irradiation is proposed. The high oxygen content (62.5% at%) and selective exposure of the facets of ultrathin 2D nanostrusctures facilitate the escape of large amounts of oxygen atoms on bismuth nanosheets from surface, forming massive oxygen vacancies and generating reactive oxygen species that explode under the action of X-rays. Moreover, the exposure of almost all atoms to environmental factors and the nature of oxycarbonates makes the nanosheets easily degrade into biocompatible species. In vivo studies demonstrate that nanosheets could induce apoptosis in cancer cells after low dose of X-ray irradiation without causing any damage to the liver or kidney. The tumor growth inhibition effect of radiotherapy increases from 49.88% to 90.76% with the help of bismuth oxycarbonate nanosheets. This work offers a promising future for nanosheet-based clinical radiotherapies of malignant cancers.
Assuntos
Bismuto , Nanoestruturas , Oxigênio , Bismuto/química , Oxigênio/química , Animais , Nanoestruturas/química , Humanos , Neoplasias/terapia , Camundongos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacosRESUMO
Accurate cellular-recognition based disease therapy is of significance for precision medicine. However, except of specific antibody-coupling strategy, very few probes have been reported to efficiently discriminate normal cells and lesion cells through cellular microenvironment. Herein, we proposed a glucose selectively-lightened upconversion nanoprobe to recognize cancer cells from a pile of normal cells based on Warburg effect, that indicated a heightened demand for glucose intake for cancer cells. The nanoprobes were constructed by mesoporous silica-coated upconversion nanoparticles (UCNP@mSiO2) with the crucial incorporation of a glucose-responsive modality, benzoboric acid (BA)-modified fluorescein molecules (FITC-BA). In cancer cells, the presence of elevated glucose concentrations triggered the transformation of FITC-BA to FITC-Glucose to recover nanoprobes' luminescence, however, the nanoprobes exhibited a shielded luminescent effect in healthy cells. To validate the hypothesis of accurate cellular-discrimination, a photodynamic therapy modality, riboflavin, with a specific ratio were also loaded into above UCNP@mSiO2 nanoprobes for effective production of reactive oxygen species to kill cells. It was found that 97.8% of cancer cells were cleaned up, but normal cells retained a nearly 100% viability after 10 min laser illumination. By leveraging the metabolic disparity from Warburg effect, the nanoprobes offer a highly accurate cellular discrimination, and significantly mitigate "off-target" damage commonly associated with conventional therapies.
Assuntos
Nanopartículas , Fluoresceína-5-Isotiocianato , Luz , Linhagem Celular Tumoral , LuminescênciaRESUMO
Photodynamic therapy is known for its non-invasiveness to significantly reduce undesired side effects on patients. However, the infiltration and invasiveness of tumor growth are still beyond the specificity of traditional light-controlled photodynamic therapy (PDT), which lacks cellular-level accuracy to tumor cells, possibly leading to "off-target" damage to healthy tissues such as the skin or immune cells infiltrated. Here, upconversion nanoparticles (UCNPs) were co-encapsulated with manganese dioxide (MnO2) by amphiphilic polymers poly(styrene-co-methyl acrylate) (PSMA) and further coated with photosensitizer (riboflavin)-loaded mesoporous silica (C@S/V). The C@S/V nanoprobes exhibited shielded upconversion luminescence in normal conditions (pH 7.4, no hydroperoxide (H2O2)) under 980-nm irradiation and thus minimal reactive oxygen production from riboflavin. However, the excess H2O2 (1 mM) and acidic environment (pH 5.5) could decompose the MnO2 within the C@S/V, resulting in remarkable enhancement of upconversion luminescence and a favorable hypoxia-relieving condition for PDT, providing a spatiotemporal signal for therapy initiation. The C@S/V nanoprobes were applied to the co-culture of normal cells (HEK293) and pancreatic cancer cells (Panc02) and performed a selective killing on Panc02 under the 980-nm irradiation. By using the "double-safety" strategy, a responsive C@S/V nanoprobe was designed by the selective activation of acidic and H2O2-rich conditions and 980-nm irradiation for spatiotemporally selective photodynamic therapy with cellular-level accuracy.
Assuntos
Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Óxidos , Compostos de Manganês , Peróxido de Hidrogênio , Células HEK293 , RiboflavinaRESUMO
Optogenetics-based synthetic biology holds great promise as a cell-based therapy strategy for many clinical incurable diseases; however, precise control over genetic expression strength and timing through disease state-related closed-loop regulation remains a challenge due to the lack of reversible probes to indicate real-time metabolite fluctuations. Here, based on a novel mechanism of analyte-induced hydrophobicity regulation of energy acceptors confined in mesoporous silica, we developed a smart hydrogel platform comprising glucose reversible responsive upconversion nanoprobes and optogenetic engineered cells, in which the upconverted blue light strength was adaptively tuned through blood glucose levels to control optogenetic expressions for insulin secretion. The intelligent hydrogel system enabled convenient maintenance of glycemic homeostasis through simple near-infrared illuminations without any additional glucose concentration monitoring, which efficiently avoided genetic overexpression-induced hypoglycemia. This proof-of-concept strategy efficiently combines diagnostics with optogenetics-based synthetic biology for mellitus therapy, opening up a new avenue for nano-optogenetics.
Assuntos
Controle Glicêmico , Raios Infravermelhos , Biologia Sintética , Secreção de Insulina , GlucoseRESUMO
Hydrogen peroxide (H2O2) is considered a significant biomarker in various diseases and could induce deleterious health problems at irregular physiological concentrations. Therefore, developing a simple, efficient biocompatible nanoprobe for trace amount H2O2 detection with high sensitivity and specificity is of great help for early diagnosis and therapeutics. Herein, we designed amphiphilic poly(styrene-co-maleic anhydride) (PMSA)-encapsulated nanoclusters composed of upconversion nanoparticles (UCNPs) and manganese dioxide nanoparticles (MnO2 NPs) at a specific ratio to produce a near-infrared (NIR) excited luminescent nanoprobe for H2O2 detection. Our results revealed that the MnO2 NPs tended to experience catalytic decomposition when exposed to H2O2, while the UCNPs were retained inside the PSMA encapsulation, causing recovery of the UCNP emission band at 470 nm in accordance with H2O2 concentration. This luminescence recovery was linearly dependent on H2O2 concentrations, yielding a limit of detection (LOD) of 20 nM. The easy-to-interpret H2O2 nanoprobe also proved high selectivity in the presence of other interfering substances, and biocompatibility and water-dispersibility, making it an ideal candidate for real-time detection of disease-related H2O2 in living organisms.
Assuntos
Nanopartículas , Óxidos , Peróxido de Hidrogênio , Compostos de Manganês , Transferência Ressonante de Energia de Fluorescência/métodos , PolímerosRESUMO
Correction for 'Surface lanthanide activator doping for constructing highly efficient energy transfer-based nanoprobes for the on-site monitoring of atmospheric sulfur dioxide' by Cuilan Zhang et al., Analyst, 2020, 145, 537-543, https://doi.org/10.1039/C9AN01725A.
RESUMO
Glucagon-like peptide-1 (GLP-1), as a molecular therapeutic, induces glucose-dependent stimulation of insulin secretion, which has drawn significant attention in treating type II diabetes. However, it always suffers from hurdles such as short half-lives or instability. Thus, producing such therapeutics endogenously, as and when needed, is beneficial. Optogenetics-based production of GLP-1 offers an attractive alternative, wherein, the cell lines such as HEK293T can be genetically modified to bring the expression of the gene of interest under visible light control. However, the need for blue light for activation necessitates the implantation of invasive optical fibers owing to high tissue scattering and low depth of penetration through biological tissue at this wavelength. Here, we overcome this problem by proposing an upconversion nanoparticle (UCNP)-based system. HEK293T cells, rewired to produce GLP-1 under blue light illumination, were co-encapsulated with UCNPs in a hydrogel. The UCNPs act as near-infrared (NIR) to blue light nano-transducers, allowing deep penetration toward implementing a tether-free optogenetic gene expression platform. This platform is particularly powerful for thick gel implants (>3 mm) that cannot be illuminated throughout using a blue light source. Moreover, the GLP-1 produced in this platform was sufficient to increase insulin secretion in rat insulinoma cells, providing a powerful and controllable therapeutic tool for diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Nanopartículas , Humanos , Optogenética , Hidrogéis , Secreção de Insulina , Células HEK293 , Raios InfravermelhosRESUMO
Precise control of energy migration between sensitizer ions and activator ions in lanthanide-doped upconversion nanoparticles (UCNPs) nowadays has been extensively investigated to achieve efficient photon upconversion. However, these UCNPs generally emit blue, green or red light only under fixed excitation conditions. In this work, regulation of the photon transition process between different energy levels of a single activator ion to obtain tunable upconversion fluorescence under different excitation conditions is achieved by introducing a modulator ion. The cross-relaxation process between modulator ion and activator ion can be controlled to generate tunable luminescence from the same lanthanide activator ion under excitation at different wavelengths or with different laser power density and pulse frequency. This strategy has been tested and proven effective in two different nanocrystal systems and its usefulness has been demonstrated for high-level optical encryption.
Assuntos
Elementos da Série dos Lantanídeos , Nanopartículas , Íons , Elementos da Série dos Lantanídeos/química , Luz , Luminescência , Nanopartículas/químicaRESUMO
A novel nanoassembly was constructed through encapsulating upconversion nanoparticles (UCNPs) into a metal-organic framework structure (ZIF-8), in which doxorubicin (DOX) was absorbed into pores of ZIF-8. The blue emission of UCNPs was quenched by DOX through the fluorescence resonance energy transfer (FRET) strategy. When the nanoprobe was exposed to food samples with different pH values, ZIF-8 collapsed to release DOX molecules, resulting in upconversion recovery. The porous structure of ZIF-8 provides abundant space for DOX absorption, which significantly improves the detection capacities and accuracy. It is shown that the probe has a good linear relationship when pH values vary from 2.5 to 7.4, and can distinguish pH variations as low as 0.5 in real samples. This strategy has been successfully used to determine food spoilage by determination of pH variations.
Assuntos
Doxorrubicina/análise , Contaminação de Alimentos/análise , Estruturas Metalorgânicas/química , Nanopartículas/química , Vinho/análise , Transferência Ressonante de Energia de Fluorescência , Concentração de Íons de HidrogênioRESUMO
Sensitive and selective detection of hypochlorite is in great demand for food safety, especially in fresh cold chain products. However, the detection limit of traditional visible emission-based strategies cannot satisfy the requirement of ultrasensitive analysis in practical applications. In this work, we explored a novel luminescent nanoprobe in the near-infrared-II (NIR-II) window to greatly improve the hypochlorite detection limit for analysis of real milk samples, which was based on the fluorescence resonance energy-transfer process between the hypochlorite-responsive dye (FD1080) and the lanthanide-doped downconverted nanoparticles. Specifically, the NIR-II luminescence from Yb ions was first suppressed by FD1080 due to the energy-transfer mechanism. In the presence of hypochlorite, FD1080 was bleached to recover the luminescence. As a proof-of-concept, the optimal nanoprobe exhibited a linear luminescence recovery in the range of 0.1-1 nM with the detection limit of 0.0295 nM for hypochlorite. Real milk sample detection experiments showed that the probe had good accuracy and precision.
Assuntos
Elementos da Série dos Lantanídeos , Nanopartículas , Transferência Ressonante de Energia de Fluorescência , Ácido Hipocloroso , LuminescênciaRESUMO
The development of precise medicine requires diagnostic probes to simultaneously satisfy an excellent detection limit and a wide linear analysis range because of enormous individual-discrepancy of disease biomarker concentrations, yet it remains challenging. Herein, an upconverison nanoprobe with a luminescence ratio flexibly tailored was designed for ultrasensitive monitoring exhaled nitric oxide to indicate the clinical course of asthma. Two independent emissions from the same nanoprobe can be discretionarily modulated to vary their intensity ratios for adapting different analysis requirements. Delightfully, this novel nanoprobe demonstrated a 100-fold lower detection limit compared with the traditional ratiometric fluorescence manner and a more broad linear detection range from the subpart per billion (ppb) level to hundreds of ppb. This ratio-adjustable fluorescence detection strategy holds great potential for miscellaneous disease diagnosis applications.
Assuntos
Transferência Ressonante de Energia de Fluorescência , LuminescênciaRESUMO
Lateral flow assay (LFA) has played pivotal roles in many emergency public safety incidents, such as coronavirus disease diagnostics; however, the present double-line (test and control line) design strategy for LFA strips greatly restricts their applications in high-throughput quantitative analysis because the limited sample diffusion distance on the strips constrains the number of test/control lines. Herein, a novel single-line-based LFA (sLFA) strip, which combines test and control line, is developed by exploiting an orthogonal emissive upconversion nanoparticle (UCNP) as a signal reporter on the test line, where one emission can be used as a reporting signal and the other as a calibrating signal. This UCNP-based test line with an interior reference also can play a validating role as a control line, and hence capturing antibodies are not needed for control lines, greatly saving fabrication costs. As a proof-of-concept, this novel sLFA strip is successfully explored to accurately and rapidly detect aflatoxin B1. Moreover, due to the removal of control lines, such a novel strategy greatly reduces the strip size, facilitating the design of a testing array for multiple detections of different samples. The test line herein is designed in a ring shape, and several test rings are assembled to be a chip for the testing of multiple samples. To our knowledge, this is the first demonstration of single-line-based LFA strips, which will significantly improve the detection capacities and accuracies and reduce the testing costs of LFA strips in real sample applications ranging from food analysis to in vitro diagnostics.
Assuntos
Aflatoxina B1/análise , Técnicas Biossensoriais/métodos , Nanopartículas Metálicas/química , Aflatoxina B1/imunologia , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Técnicas Biossensoriais/instrumentação , COVID-19/diagnóstico , COVID-19/virologia , Análise de Alimentos/métodos , Ouro/química , Humanos , Medições Luminescentes , SARS-CoV-2/isolamento & purificaçãoRESUMO
A novel hybrid supramolecular system with near-infrared photon-excited energy transfer has been successfully constructed, relying on the assistance of upconversion nanoparticles in platinum(ii)-based supramolecular polymers. The resulting hybrid system is capable of displaying intriguing photo-switchable and sequential energy transfer features.
RESUMO
Three-dimensional (3D) porous zinc (Zn) with a moderate degradation rate is a promising candidate for biodegradable bone scaffolds. However, fabrication of such scaffolds with adequate mechanical properties remains a challenge. Moreover, the composition, crystallography and microstructure of the in vivo degradation products formed at or near the implant-bone interface are still not precisely known. Here, we have fabricated porous Fe@Zn scaffolds with skeletons consisting of an inner core layer of Fe and an outer shell layer of Zn using template-assisted electrodeposition technique, and systematically evaluated their porous structure, mechanical properties, degradation mechanism, antibacterial ability and in vitro and in vivo biocompatibility. In situ site-specific focused ion beam micromilling and transmission electron microscopy were used to identify the in vivo degradation products at the nanometer scale. The 3D porous Fe@Zn scaffolds show similar structure and comparable mechanical properties to human cancellous bone. The degradation rates can be adjusted by varying the layer thickness of Zn and Fe. The antibacterial rates reach over 95% against S. aureus and almost 100% against E. coli. A threshold of released Zn ion concentration (~ 0.3 mM) was found to determine the in vitro biocompatibility. Intense new bone formation and ingrowth were observed despite with a slight inflammatory response. The in vivo degradation products were identified to be equiaxed nanocrystalline zinc oxide with dispersed zinc carbonate. This study not only demonstrates the feasibility of porous Fe@Zn for biodegradable bone implants, but also provides significant insight into the degradation mechanism of porous Zn in physiological environment.
Assuntos
Osso Esponjoso , Zinco , Escherichia coli , Humanos , Teste de Materiais , Porosidade , Staphylococcus aureus , Alicerces TeciduaisRESUMO
Accurate onsite profiling of fluoroquinolone antibiotics (FQs) is of vital significance for ensuring food safety and estimating environmental pollution. Here, we propose a smartphone-based QD ratiometric fluorescence-sensing system to precisely report the level of FQs. As a proof of concept, we chose gatifloxacin (GFLX, a typical member of FQs) as the model for the analytical target, which could effectively trigger the fluorescence color variation of QDs from bright yellow-green (â¼557 nm) to blue (â¼448 nm) through the photoinduced electron-transfer (PET) process, thus yielding an evident ratiometric response. Based on this, the level of GFLX can be reported within a wide linear range from 0.85 nM to 3.6 µM. Moreover, this assay owns a high sensitivity with a low detection limit of 0.26 nM for GFLX and a quick sample-to-answer monitoring time of 5.0 min, manifesting that this platform could be fully qualified for onsite requirements. Interestingly, this portable device has successfully been applied for the onsite detection of GFLX in real food (i.e., milk and drinking water) and environmental (i.e., fish-farming water) samples with acceptable results. This developed platform offers a great promise for the point-of-care detection of FQ residues in practical application with the merits of being label-free, low-cost, and rapid, thus opening a new pathway for the onsite evaluation of food safety and environmental health.
Assuntos
Antibacterianos/isolamento & purificação , Técnicas Biossensoriais , Monitoramento Ambiental/métodos , Fluoroquinolonas/isolamento & purificação , Antibacterianos/química , Poluição Ambiental/análise , Fluorescência , Fluoroquinolonas/química , Inocuidade dos Alimentos , Humanos , SmartphoneRESUMO
Upconversion nanoparticles (UCNPs) doped with lanthanide ions that possess ladder-like energy levels can give out multiple emissions at specific ultra-violet or visible wavelengths irrespective of excitation light. However, precisely controlling energy migration processes between different energy levels of the same lanthanide ion to generate switchable emissions remains elusive. Herein, a novel dumbbell-shaped UCNP is reported with upconverted red emission switched to green emission when excitation wavelength changed from 980 to 808 nm. The sensitizer Yb ions are doped with activator Er ions and energy modulator Mn ions in NaYF4 core nanocrystal coated with an inner NaYF4 :Yb shell to generate red emission after harvesting 980 nm excitation light, while an outer NaNdF4 :Yb shell is coated to form a dumbbell shape to generate green emission upon 808 nm excitation. Such specially designed UCNPs with switchable green and red emissions are further explored for imaging of latent fingerprint and detection of explosive residues in the fingerprint simultaneously. This work suggests a novel research interest in fine-tuning of upconversion emissions through precisely controlling energy migration processes of the same lanthanide activator ion. Furthermore, use of these nanoparticles in other applications such as simultaneous dual-color imaging or orthogonal bidirectional photoactivation can be explored.
RESUMO
The sensitive and on-site detection of sulfur dioxide (SO2) is in great demand in the fields of food safety and environmental protection. Here, we developed a novel upconversion nanoprobe based on the luminescence energy transfer mechanism for monitoring the atmospheric SO2 concentrations. The lanthanide emitters, Tm3+ ions, were optimized to be doped on the surface layer of the upconversion nanoparticles to improve their energy transfer efficiency by minimizing the distance between the emitters and the surface quencher, a cyanine dye. As a proof-of-concept, the optimal nanoprobe was utilized to detect SO2 water derivatives, bisulfite ions, exhibiting a linear luminescence increase in the range of 1 nM to 10 nM. Furthermore, we assembled the cyanine-modified upconversion nanoparticles onto a test paper, and used a smartphone-based detection platform to achieve portable and visual detection of SO2. The test paper showed a strong luminescence stability, homogeneity and good anti-interference. The limit of detection for SO2 gas was found to be 1 ng L-1. This novel upconversion test paper was also demonstrated to directly monitor the concentration of SO2 gas in atmosphere.
RESUMO
A smartphone-integrated ratiometric fluorescent sensing system (DPA-Ce-GMP-Eu) for visual and point-of-care testing (POCT) of tetracycline with high sensitivity and accuracy was developed. The blue fluorescence of DPA-Ce-GMP was changed into red by doping with Eu3+ duo to the energy transfer from Ce3+ to Eu3+. Upon exposure to tetracycline, coordination between Eu3+ and tetracycline blocks energy transfer from Ce3+ to Eu3+, converting the fluorescent color from red to blue. The tetracycline detection can be realized within a wide concentration range from 0.01⯵M to 45⯵M. The limit of detection (LOD) reaches as low as 6.6â¯nM. To realize quantitative point-of-care detection in real samples, a portable device with smartphone as signal reader and analyzer is further designed to integrate with the DPA-Ce-GMP-Eu sensing platform. The Color Picker APP installed in the smartphone can convert the Red, Green and Blue (RGB) channels of the fluorescence images into digital values. With milk as real sample, tetracycline can be on-site detected with LOD of 10.8â¯nM. This developed platform presents a great promise for POCT in practical application with merits of low cost, easy carry, simple operation, and excellent selectivity and repeatability.