RESUMO
Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R2 = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients' samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic.
Assuntos
Endopeptidases , Cirrose Hepática , Imageamento por Ressonância Magnética , Proteínas de Membrana , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Endopeptidases/metabolismo , Proteínas de Membrana/metabolismo , Gelatinases/metabolismo , Compostos Organometálicos/química , Masculino , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/metabolismo , Feminino , Compostos Heterocíclicos/química , Pessoa de Meia-Idade , Animais , Meios de Contraste/químicaRESUMO
The clearance of senescent cells may be detrimental to low cell density diseases, such as intervertebral disc degeneration (IVDD), and rejuvenating these cells presents a formidable obstacle. In this study, we investigate a mild-alkalization strategy employing magnesium boride-alginate (MB-ALG) hydrogels to rejuvenate senescent cells associated with age-related diseases. MB-ALG hydrogels proficiently ensnare senescent cells owing to their surface roughness. The hydrolysis of MB-ALG hydrogels liberates hydroxide ions (OH-), effecting a transition from an acidic microenvironment (pH â¼ 6.2) to a mildly alkaline state (pH â¼ 8.0), thereby fostering senescent cell proliferation via activation of the PI3K/Akt/mTOR pathway. Additionally, H2 aids in ROS clearance, which reduces cellular oxidative stress. And, Mg2+ rejuvenates senescent cells by inhibiting Ca2+ influx and fine-tuning the sirt1-p53 signaling pathways. Both in vitro and in vivo experiments conducted on rat intervertebral discs corroborate the sustained antisenescence and rejuvenation properties of MB-ALG hydrogels, with effects persisting for up to 12 weeks postoperation. These discoveries elucidate the role of mild-alkalization in dictating cellular destiny and provide key insights for addressing age-related diseases.
Assuntos
Alginatos , Senescência Celular , Hidrogéis , Alginatos/química , Alginatos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Senescência Celular/efeitos dos fármacos , Ratos , Proliferação de Células/efeitos dos fármacos , Ratos Sprague-Dawley , Compostos de Boro/química , Compostos de Boro/farmacologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Magnésio/química , Magnésio/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
The manipulation of cell surface receptors' activity will open a new frontier for drug development and disease treatment. However, limited by the desensitization of drugs, effective physical intervention strategy remains challenging. Here, the controllable internalization of transient receptor potential vanilloid 1 (TRPV1) on neural cells by local piezoelectric field is reported. Single-cell-level local electric field is construct by synthesizing piezoelectric BiOIO3 nanosheets (BIONSs). Upon a mild ultrasound of 0.08 W cm-2, an electric field of 15.29 µV is generated on the surface of BIONSs, further inducing TRPV1 internalization in 5 min. The as-downregulated TRPV1 expression results in the reduction of Ca2+ signal in a spinal neuron and the inhibition of the activity of wide range dynamic neurons, therefore effectively preventing the transmission of cancer-induced bone pain (CIBP). This strategy not only charts a new course for CIBP alleviation, but also introduces a promising nanotechnology for regulating cell surface receptors, showing significant potential in neuropathological and receptor-related diseases.
Assuntos
Dor do Câncer , Canais de Cátion TRPV , Animais , Canais de Cátion TRPV/metabolismo , Dor do Câncer/tratamento farmacológico , Dor do Câncer/metabolismo , Camundongos , Analgesia/métodos , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Humanos , Linhagem Celular Tumoral , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Nanoestruturas/químicaRESUMO
To fulfil the demands of rapid proliferation, tumour cells undergo significant metabolic alterations. Suppression of hyperactivated metabolism has been proven to counteract tumour growth. However, whether the reactivation of downregulated metabolic pathways has therapeutic effects remains unexplored. Here we report a nutrient-based metabolic reactivation strategy for effective melanoma treatment. L-Tyrosine-oleylamine nanomicelles (MTyr-OANPs) were constructed for targeted supplementation of tyrosine to reactivate melanogenesis in melanoma cells. We found that reactivation of melanogenesis using MTyr-OANPs significantly impeded the proliferation of melanoma cells, primarily through the inhibition of glycolysis. Furthermore, leveraging melanin as a natural photothermal reagent for photothermal therapy, we demonstrated the complete eradication of tumours in B16F10 melanoma-bearing mice through treatment with MTyr-OANPs and photothermal therapy. Our strategy for metabolism activation-based tumour treatment suggests specific nutrients as potent activators of metabolic pathways.
Assuntos
Melanoma Experimental , Tirosina , Animais , Camundongos , Melanoma Experimental/terapia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Linhagem Celular Tumoral , Tirosina/metabolismo , Melaninas/metabolismo , Proliferação de Células/efeitos dos fármacos , Humanos , Micelas , Melanoma/terapia , Melanoma/metabolismo , Melanoma/patologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Terapia Fototérmica/métodos , Glicólise/efeitos dos fármacos , Nutrientes/metabolismo , Camundongos Endogâmicos C57BLRESUMO
The limited analgesic efficiency of magnesium restricts its application in pain management. Here, we report boron hydride (BH) with ion currents rectification activity that can enhance the analgesic efficiency of magnesium without the risks of drug tolerance or addiction. We synthesize MgB2, comprising hexagonal boron sheets alternating with Mg2+. In pathological environment, Mg2+ is exchanged by H+, forming two-dimensional borophene-analogue BH sheets. BH interacts with the charged cations via cation-pi interaction, leading to dynamic modulation of sodium and potassium ion currents around neurons. Additionally, released Mg2+ competes Ca2+ to inhibit its influx and neuronal excitation. In vitro cultured dorsal root neurons show a remarkable increase in threshold potential from the normal -35.9â mV to -5.9â mV after the addition of MgB2, indicating potent analgesic effect. In three typical pain models, including CFA-induced inflammatory pain, CINP- or CCI-induced neuropathic pain, MgB2 exhibits analgesic efficiency approximately 2.23, 3.20, and 2.0â times higher than clinical MgSO4, respectively, and even about 1.04, 1.66, and 1.95â times higher than morphine, respectively. The development of magnesium based intermetallic compounds holds promise in addressing the non-opioid medical need for pain relief.
Assuntos
Magnésio , Magnésio/química , Animais , Nanoestruturas/química , Camundongos , Analgésicos/química , Analgésicos/farmacologia , Boroidretos/químicaRESUMO
Organic photoelectrochemical transistor (OPECT) has shown substantial potential in the development of next-generation bioanalysis yet is limited by the either-or situation between the photoelectrode types and the channel types. Inspired by the dual-photoelectrode systems, we propose a new architecture of dual-engine OPECT for enhanced signal modulation and its biosensing application. Exemplified by incorporating the CdS/Bi2S3 photoanode and Cu2O photocathode within the gate-source circuit of Ag/AgCl-gated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) channel, the device shows enhanced modulation capability and larger transconductance (gm) against the single-photoelectrode ones. Moreover, the light irritation upon the device effectively shifts the peak value of gm to zero gate voltage without degradation and generates larger current steps that are advantageous for the sensitive bioanalysis. Based on the as-developed dual-photoelectrode OPECT, target-mediated recycling and etching reactions are designed upon the CdS/Bi2S3, which could result in dual signal amplification and realize the sensitive microRNA-155 biodetection with a linear range from 1 fM to 100 pM and a lower detection limit of 0.12 fM.
Assuntos
Cobre , Técnicas Eletroquímicas , Sulfetos , Tiofenos , Técnicas Eletroquímicas/instrumentação , Cobre/química , Sulfetos/química , Compostos de Cádmio/química , Técnicas Biossensoriais/instrumentação , Bismuto/química , Transistores Eletrônicos , Processos Fotoquímicos , Poliestirenos/química , MicroRNAs/análise , Eletrodos , Polímeros/químicaRESUMO
Chemodynamic therapy (CDT) is an emerging tumor microenvironment-responsive cancer therapeutic strategy based on Fenton/Fenton-like reactions. However, the effectiveness of CDT is subject to the slow kinetic rate and non-homogeneous distribution of H2 O2 . In this study, a conceptual non-metallic "Fenton-active" center construction strategy is proposed to enhance CDT efficiency using Bi0.44 Ba0.06 Na0.5 TiO2.97 (BNBT-6) nanocrystals. The separated charge carriers under a piezoelectric-induced electric field synchronize the oxidation of H2 O and reduction of H2 O2 , which consequently increases hydroxyl radical (·OH) yield even under low H2 O2 levels. Moreover, acceptor doping induces electron-rich oxygen vacancies to facilitate the dissociation of H2 O2 and H2 O and further promote ·OH generation. In vitro and in vivo experiments demonstrate that BNBT-6 induces extensive intracellular oxidative stress and enhances cell-killing efficiency by activating necroptosis in addition to the conventional apoptotic pathway. This study proposes a novel design approach for nanomaterials used in CDT and presents a new treatment strategy for apoptosis-resistant tumors.
Assuntos
Apoptose , Neoplasias , Humanos , Ultrassonografia , Eletricidade , Elétrons , Radical Hidroxila , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Peróxido de Hidrogênio , Microambiente TumoralRESUMO
Chemodynamic therapy (CDT) based on generating reactive oxygen species (ROS) is promising for cancer treatment. However, the intrinsic H2O2 is deficient for CDT, and glutathione (GSH) eliminates ROS to protect tumor cells from ROS cytotoxicity. Herein, we propose a strategy to switch the electron flow direction of GSH for O2 reduction and ROS generation rather than ROS clearance by using P(DA-Fc) nanoparticles, which are polymerized from ferrocenecarboxylic acid (Fc) coupled dopamine. P(DA-Fc) NPs with phenol-quinone conversion ability mimic NOX enzyme to deprive electrons from GSH to reduce O2 for H2O2 generation; the following â¢OH release can be triggered by Fc. Semiquinone radicals in P(DA-Fc) are significantly enhanced after GSH treatment, further demonstrated with strong single-electron reduction ability by calculation. In vitro and in vivo experiments indicate that P(DA-Fc) can consume intrinsic GSH to produce endogenous ROS; ROS generation strongly depends on GSH/pH level and eventually causes tumor cell death. Our work makes the first attempt to reverse the function of GSH from ROS scavenger to ROS producer, explores new roles of PDA-based nanomaterials in CDT beyond photothermal reagents and drug carriers, and provides a new strategy to improve the efficiency of CDT. STATEMENT OF SIGNIFICANCE: P(DA-Fc) nanoparticles performing tumor microenvironment response capacity and tumor reductive power utilize ability were fabricated for CDT tumor suppression. After endocytosis by tumor cells, P(DA-Fc) deprived GSH of electrons for H2O2 and â¢OH release, mimicking the intrinsic ROS production conducted by NADPH, further inducing tumor cell necrosis and apoptosis. Our work makes the first attempt to reverse the function of GSH from ROS scavenger to producer, explores new functions of PDA-based nanomaterials in CDT beyond photothermal reagents and drug carriers, and provides a new strategy to improve CDT efficiency.
Assuntos
Nanopartículas , Neoplasias , Humanos , Elétrons , Espécies Reativas de Oxigênio , Polifenóis/farmacologia , Peróxido de Hidrogênio , Oxirredução , Portadores de Fármacos , Linhagem Celular Tumoral , Microambiente Tumoral , Glutationa , Neoplasias/tratamento farmacológicoRESUMO
Positive computed tomography (CT) contrast nanoagent has significant applications in diagnosing tumors. However, the sensitive differentiation between hepatoma and normal liver tissue remains challenging. This challenge arises primarily because both normal liver and hepatoma tissues capture the nanoagent, resulting in similar positive CT contrasts. Here, a strategy for fusing positive and negative CT contrast nanoagent is proposed to detect hepatoma. A nanoagent Hf-MOF@AB@PVP initially generates a positive CT contrast signal of 120.3 HU in the liver. Subsequently, it can specifically respond to the acidic microenvironment of hepatoma to generate H2 , further achieving a negative contrast of -96.0 HU. More importantly, the relative position between the negative and positive signals area is helpful to determine the location of hepatoma and normal liver tissues. The distinct contrast difference of 216.3 HU and relative orientation between normal liver and tumor tissues are meaningful to sensitively distinguish hepatoma from normal liver tissue utilizing CT imaging.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Meios de Contraste , Microambiente TumoralRESUMO
"Structure subserves function" is one fundamental biological maxim, and so the biological membrane that delimits the regions primarily serves as the margin between life and death for individual cells. Here, an Oswald ripening mechanism-guided solvothermal method was proposed for the synthesis of uniform MnS nanocapsules assembled with metastable γ-MnS nanocrystals. Through designing the physicochemical properties, MnS nanocapsules would disaggregate into small γ-MnS nanocrystals in a tumor acidic environment, with the surface potential switched from negative to positive, thus showing conspicuous delivery performance. More significantly, the specific accumulation of Mn2+ in mitochondria was promoted due to the downregulation of mitochondrial calcium uptake 1 (MICU1) by the formed H2S, thus leading to serious mitochondrial Mn-poisoning for membrane permeability increase and then tumor apoptosis. This study provides a synthesis strategy of metal sulfide nanocapsules and encourages multidisciplinary researchers to focus on ion-cancer crosstalk for the development of an antitumor strategy.
Assuntos
Membranas Mitocondriais , Nanocápsulas , Membranas Mitocondriais/metabolismo , Mitocôndrias , Apoptose , PermeabilidadeRESUMO
DNA intercalation has increasingly been studied for various scenario implementations due to the diverse functions of DNA/intercalators. Nascent organic photoelectrochemical transistor (OPECT) biosensing taking place in organic electronics and photoelectrochemical bioanalysis represents a promising technological frontier in the arena. In this work, we first devise DNA intercalation-enabled OPECT for miRNA detection with a superior gain up to 17100. Intercalation of [Ru(bpy)2dppz]2+ within the miRNA-initiated hybrid chain reaction (HCR)-derived duplex DNA is realized for producing anodic photocurrent upon light stimulation, causing the corresponding target-dependent alternation in gate voltage (VG) and hence the modulated channel current (IDS) of poly (3,4-ethylenedioxythiophene) doped with poly (styrene sulfonate) (PEDOT:PSS) under specific drain voltage (VDS) for quantitative miRNA-21 analysis, which shows a wide linear relationship and a low detection limit of 5.5 × 10-15 mol L-1. This study features the DNA intercalation-enabled organic electronics with superior gain and is envisaged to attract more attention to explore DNA adducts for innovative bioelectronics and biosensing, given the diverse DNA binders with multiple functions.
Assuntos
Técnicas Biossensoriais , MicroRNAs , DNA/análise , Estireno , Substâncias IntercalantesRESUMO
Organic photoelectrochemical transistor (OPECT) biosensing represents a new platform interfacing optoelectronics and biological systems with essential amplification, which, nevertheless, are concentrated on depletion-type operation to date. Here, a polymer dot (Pdot)-gated accumulation-type OPECT biosensor is devised and applied for sensitive urea detection. In such a device, the as-designed Pdot/poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] (PTAA) is validated as a superior gating module against the diethylenetriamine (DETA) de-doped poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) channel, and the urea-dependent status of Pdots has been shown to be sensitively correlated with the device's response. High-performance urea detection is thus realized with a wide linear range of 1 µM-50 mM and a low detection limit of 195 nM. Given the diversity of the Pdot family and its immense interactions with other species, this work represents a generic platform for developing advanced accumulation-type OPECT and beyond.
Assuntos
Técnicas Biossensoriais , Polímeros , Ureia , Estireno , OuroRESUMO
Sustained signal activation by hydroxyl radicals (â OH) has great significance, especially for tumor treatment, but remains challenging. Here, a built-in electric field (BIEF)-driven strategy was proposed for sustainable generation of â OH, thereby achieving long-lasting chemodynamic therapy (LCDT). As a proof of concept, a novel Janus-like Fe@Fe3 O4 -Cu2 O heterogeneous catalyst was designed and synthesized, in which the BIEF induced the transfer of electrons in the Fe core to the surface, reducing ≡Cu2+ to ≡Cu+ , thus achieving continuous Fenton-like reactions and â OH release for over 18â h, which is approximately 12 times longer than that of Fe3 O4 -Cu2 O and 72 times longer than that of Cu2 O nanoparticles. In vitro and in vivo antitumor results indicated that sustained â OH levels led to persistent extracellular regulated protein kinases (ERK) signal activation and irreparable oxidative damage to tumor cells, which promoted irreversible tumor apoptosis. Importantly, this strategy provides ideas for developing long-acting nanoplatforms for various applications.
Assuntos
Nanopartículas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Nanopartículas/química , Radical Hidroxila/metabolismo , Estresse Oxidativo , Peróxido de Hidrogênio/metabolismo , Linhagem Celular TumoralRESUMO
The spatiotemporal characterization of signaling crosstalk between subcellular organelles is crucial for the therapeutic effect of malignant tumors. Blocking interactive crosstalk in this fashion is significant but challenging. Herein, a communication interception strategy is reported, which blocks spatiotemporal crosstalk between subcellular organelles for cancer therapy with underlying molecular mechanisms. Briefly, amorphous-core@crystalline-shell Fe@Fe3 O4 nanoparticles (ACFeNPs) are fabricated to specifically block the crosstalk between lysosomes and endoplasmic reticulum (ER) by hydroxyl radicals generated along with their trajectory through heterogeneous Fenton reaction. ACFeNPs initially enter lysosomes and trigger autophagy, then continuous lysosomal damage blocks the generation of functional autolysosomes, which mediates ER-lysosome crosstalk, thus the autophagy is paralyzed. Thereafter, released ACFeNPs from lysosomes induce ER stress. Without the alleviation by autophagy, the ER-stress-associated apoptotic pathway is fully activated, resulting in a remarkable therapeutic effect. This strategy provides a wide venue for nanomedicine to exert biological advantages and confers new perspective for the design of novel anticancer drugs.
Assuntos
Estresse do Retículo Endoplasmático , Neoplasias , Neoplasias/metabolismo , Autofagia , Lisossomos/metabolismo , HumanosRESUMO
Bacteria and excessive inflammation are two main factors causing non-healing wounds. However, current studies have mainly focused on the inhibition of bacteria survival for wound healing while ignoring the excessive inflammation induced by dead bacteria-released lipopolysaccharide (LPS) or peptidoglycan (PGN). Herein, a boron-trapping strategy has been proposed to prevent both infection and excessive inflammation by synthesizing a class of reactive metal boride nanoparticles (MB NPs). Our results show that the MB NPs are gradually hydrolyzed to generate boron dihydroxy groups and metal cations while generating a local alkaline microenvironment. This microenvironment greatly enhances boron dihydroxy groups to trap LPS or PGN through an esterification reaction, which not only enhances metal cation-induced bacterial death but also inhibits dead bacteria-induced excessive inflammation both in vitro and in vivo, finally accelerating wound healing. Taken together, this boron-trapping strategy provides an approach to the treatment of bacterial infection and the accompanying inflammation.
Assuntos
Nanopartículas Metálicas , Infecção dos Ferimentos , Humanos , Peptidoglicano , Lipopolissacarídeos/toxicidade , Boro/farmacologia , Cicatrização , Bactérias , Ligante de CD40 , Inflamação , Compostos de BoroRESUMO
T lymphocytes (T cells) are essential for tumor immunotherapy. However, the insufficient number of activated T cells greatly limits the efficacy of tumor immunotherapy. Herein, we proposed an oncolytic virus-mimicking strategy to enhance T cell recruitment and activation for tumor treatment. We constructed an oncolytic virus-like nanoplatform (PolyIC@ZIF-8) that was degraded in the acidic tumor environment to release PolyIC and Zn2+ . The released PolyIC exhibited an oncolytic virus-like function that induced tumor cell apoptosis and promoted T cell recruitment and activation through a tumor antigen-dependent manner. More importantly, the released Zn2+ not only enhanced T cell recruitment by inducing CXCL9/10/11 expression but also promoted T cell activation to increase interferon-γ (INF-γ) expression by inducing the phosphorylation of ZAP-70 via a tumor antigen-independent manner. This Zn2+ -enhanced oncolytic virus-mimicking strategy provides a new approach for tumor immunotherapy.
Assuntos
Nanopartículas , Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Vírus Oncolíticos/metabolismo , Imunoterapia , Neoplasias/terapia , Antígenos de Neoplasias , Linhagem Celular TumoralRESUMO
In the field of nanomedicine, there is a tendency of matching designed nanomaterials with a suitable type of orthotopic cancer model, not just a casual subcutaneous one. Under this condition, knowing the specific features of the chosen cancer model is the priority, then introducing a proper therapy strategy using designed nanomaterials. Here, the Fenton chemistry is combined with zinc peroxide nanoparticles in the treatment of orthotopic liver cancer which has a "chemical factory" including that liver is the main place for iron storage, metabolism, and also the main metabolic sites for the majority of ingested substances, guaranteeing customized and enhanced chemodynamic therapy and normal liver cells protection as well. The good results in vitro and in vivo can set an inspiring example for exploring and utilizing suitable nanomaterials in corresponding cancer models, ensuring well-fitness of nanomaterials for disease and satisfactory therapeutic effect.
Assuntos
Neoplasias Hepáticas , Nanopartículas , Nanoestruturas , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Nanomedicina/métodos , FototerapiaRESUMO
B-mode ultrasound imaging is a significant anatomic technique in clinic, which can display the anatomic variation in tissues. However, it is difficult to evaluate the functional state of organs and display the physiological information in organisms such as the tumor acidic microenvironment (TME). Herein, inspired by the phenomenon of sonographic acoustic shadow during detecting calculus in clinic, a strategy of self-enhanced acoustic impedance difference is proposed to monitor the acidic TME. BiF3@PDA@PEG (BPP) nanoparticles can self-aggregate in a specific response to the acidic TME to form huge "stones" BiF3@PDA, resulting in an increase of local tumor density, and further causing a significant acoustic impedance difference. In in vitro experiments, the enhanced ultrasound signals change from 15.2 to 196.4 dB, which can discriminate different pH values from 7.0 to 5.0, and the sensitivity can reach to 0.2 value. In in vivo experiments, the enhanced ultrasound signal is 107.7 dB after BPP self-aggregated, displaying the weak acidic TME that has a close relationship with the size and species of the tumor. More importantly, the accuracy is away from the interference of pressure because huge "stones" BiF3@PDA change little. However, SonoVue microbubbles will diffuse and rupture under pressure, which results in false positive signals. To sum up, this strategy will be helpful to the further development of ultrasound molecular imaging.
Assuntos
Nanopartículas , Microambiente Tumoral , Acústica , Impedância Elétrica , Microbolhas , Nanopartículas/químicaRESUMO
The tumor microenvironment is a complex milieu where neurons constitute an important non-neoplastic cell type. From "cancer neuroscience," the crosstalk between tumors and neurons favors the rapid growth of both, making the cancer-nerve interaction a reciprocally beneficial process. Thus, cancer-nerve crosstalk may provide new targets for therapeutic intervention against cancer and cancer-related symptoms. We proposed a nerve-cancer crosstalk blocking strategy for metastatic bone cancer pain treatment, achieved by Mg/Al layered-double-hydroxide nanoshells (Mg/Al-LDH) with AZ-23 loaded inside and alendronate decorated outside. The pain-causing H+ is rapidly eliminated by the LDH, with neurogenesis inhibited by the antagonist AZ-23. As positive feedback, the decreased pain reverses the nerve-to-cancer Ca2+ crosstalk-related cell cycle, dramatically inhibiting tumor growth. All experiments confirm the improved pain threshold and enhanced tumor inhibition. The study may inspire multidisciplinary researchers to focus on cancer-nerve crosstalk for treating cancer and accompanied neuropathic diseases.
Assuntos
Neoplasias Ósseas , Dor do Câncer , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Dor do Câncer/tratamento farmacológico , Dor do Câncer/metabolismo , Humanos , Neurônios/metabolismo , Dor/metabolismo , Microambiente TumoralRESUMO
Timely detection of liver fibrosis by X-ray computed tomography (CT) can prevent its progression to fatal liver diseases. However, it remains quite challenging because conventional CT can only identify the difference in density instead of X-ray attenuation characteristics. Spectral CT can generate monochromatic imaging to specify X-ray attenuation characteristics of the scanned matter. Herein, an X-ray energy-dependent attenuation strategy originated from bismuth (Bi)-based nanoprobes (BiF3 @PDA@HA) is proposed for the accurate diagnosis of liver fibrosis. Bi element in BiF3 @PDA@HA can exhibit characteristic attenuation depending on different levels of X-ray energy via spectral CT, and that is challenging for conventional CT. In this study, selectively accumulating BiF3 @PDA@HA nanoprobes in the hepatic fibrosis areas can significantly elevate CT value for 40 Hounsfield units on 70 keV monochromatic images, successfully differentiating from healthy livers and achieving the diagnosis of liver fibrosis. Furthermore, the enhancement produced by the BiF3 @PDA@HA nanoprobes in vivo increases as the monochromatic energy decreases from 70 to 40 keV, optimizing the conspicuity of the diseased areas. As a proof of concept, the strategically designed nanoprobes with energy-dependent attenuation characteristics not only expand the scope of CT application, but also hold excellent potential for precise imaging-based disease diagnosis.