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1.
Bioorg Chem ; 152: 107768, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39216196

RESUMO

Alzheimer's disease is associated both with imbalances in Al3+ production and changes in viscosity in cells. Their simultaneous measurement could therefore provide valuable insights into Alzheimer's disease pathology. Their simultaneous measurement would therefore be of great value in investigating the pathological mechanism of Alzheimer's disease. We designed a fluorescent probe YM2T with AIE effect that is capable of selectively responding to Al3+ by fluorescence colormetrics and to viscosity by fluorescence "turn on" modes. Additionally, Al3+ and viscosity were simultaneously detected in PC12 cells using the low cytotoxic probe YM2T via blue and green fluorescence channels. More importantly, the YM2T probe was used to image mice with AD. Hence, the YM2T probe shows potential as a useful molecular instrument for studying the pathological impact of Al3+ and viscosity.

2.
Int J Nanomedicine ; 19: 7493-7508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39081895

RESUMO

Introduction: Lung cancer is the most common cancer worldwide, among which non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. Chemotherapy, a mainstay modality for NSCLC, has demonstrated restricted effectiveness due to the emergence of chemo-resistance and systemic side effects. Studies have indicated that combining chemotherapy with phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), can enhance efficacy of therapy. In this work, an aminated mesoporous graphene oxide (rPGO)-protoporphyrin IX (PPIX)-hyaluronic acid (HA)@Osimertinib (AZD) nanodrug delivery system (rPPH@AZD) was successfully developed for combined chemotherapy/phototherapy for NSCLC. Methods: A pH/hyaluronidase-responsive nanodrug delivery system (rPPH@AZD) was prepared using mesoporous graphene oxide. Its morphology, elemental composition, surface functional groups, optical properties, in vitro drug release ability, photothermal properties, reactive oxygen species production, cellular uptake and cell viability were evaluated. In addition, the in vivo therapeutic effect, biocompatibility, and imaging capabilities of rPPH@AZD were verified by a tumor-bearing mouse model. Results: Aminated mesoporous graphene oxide (rPGO) plays a role as a drug delivery vehicle owing to its large specific surface area and ease of surface functionalization. rPGO exhibits excellent photothermal conversion properties under laser irradiation, while PPIX acts as a photosensitizer to generate singlet oxygen. AZD acts as a small molecule targeted drug in chemotherapy. In essence, rPPH@AZD shows excellent photothermal and fluorescence imaging effects in tumor-bearing mice. More importantly, in vitro and in vivo results indicate that rPPH@AZD can achieve hyaluronidase/pH dual response as well as combined chemotherapy/PTT/PDT anti-NSCLC treatment. Conclusion: The newly prepared rPPH@AZD can serve as a promising pH/hyaluronidase-responsive nanodrug delivery system that integrates photothermal/fluorescence imaging and chemo/photo combined therapy for efficient therapy against NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Grafite , Ácido Hialurônico , Neoplasias Pulmonares , Nanocompostos , Fotoquimioterapia , Grafite/química , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Animais , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Humanos , Camundongos , Nanocompostos/química , Ácido Hialurônico/química , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Protoporfirinas/química , Protoporfirinas/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Terapia Combinada , Liberação Controlada de Fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Camundongos Nus , Porosidade , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo
3.
Gels ; 10(7)2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39057503

RESUMO

Hydrogels are widely used as excellent drug carriers in the field of biomedicine. However, their application in medicine is limited by their poor mechanical properties and softness. To improve the mechanical properties of hydrogels, a novel triple-network amphiphilic hydrogel with three overlapping crosslinking methods using a one-pot free-radical polymerization was synthesized in this study. Temperature-sensitive and pH-sensitive monomers were incorporated into the hydrogel to confer stimulus responsiveness, making the hydrogel stimuli-responsive. The successful synthesis of the hydrogel was confirmed using techniques, such as proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier-transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). In order to compare and analyze the properties of physically crosslinked hydrogels, physically-chemically double-crosslinked hydrogels, and physically-chemically clicked triple-crosslinked hydrogels, various tests were conducted on the gels' morphology, swelling behavior, thermal stability, mechanical properties, and drug loading capacity. The results indicate that the triple-crosslinked hydrogel maintains low swelling, high mechanical strength, and good thermal stability while not significantly compromising its drug delivery capability.

4.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124664, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-38901234

RESUMO

As a valuable industrial chemical, thiophenol (PhSH) is poisonous, which can be easily absorbed by the human body, leading to many serious health issues. In addition, PhSH-triggered oxidative stress is considered to be related with the pathogenesis and toxicity of PhSH. Therefore, efficient methods for monitoring PhSH and ROS production induced by PhSH in living systems are very meaningful and desired. Herein, we reasonably developed a facile dual-response fluorescent probe (HDB-DNP) by incorporating the dinitrophenyl (DNP) group into a novel methylthio-substituted salicylaldehyde azine (HDB) with AIE and ESIPT features. The probe itself was non-fluorescent owing to the strong quenching effect of DNP group. In the presence of PhSH, HDB-DNP gave an intense red fluorescence (610 nm), which can rapidly switch to green fluorescence (510 nm) upon further addition of HClO, allowing the successive detection of PhSH and HClO in two well-separated channels. HDB-DNP proved to be a very promising dual-functional probe for rapid (PhSH: < 17 min; HClO: 10 s) and selective detection of PhSH and HClO in physiological conditions with low detection limit (PhSH: 13.8 nM; HClO: 88.6 nM). Inspired by its excellent recognition properties and low cytotoxicity, HDB-DNP was successfully applied for monitoring PhSH and PhSH-induced HClO generation in living cells with satisfactory results, which may help to better understand the pathogenesis of PhSH-related diseases.


Assuntos
Corantes Fluorescentes , Ácido Hipocloroso , Estresse Oxidativo , Fenóis , Espectrometria de Fluorescência , Compostos de Sulfidrila , Corantes Fluorescentes/química , Humanos , Estresse Oxidativo/efeitos dos fármacos , Ácido Hipocloroso/análise , Compostos de Sulfidrila/química , Fenóis/química , Fenóis/farmacologia , Células HeLa
5.
ACS Appl Mater Interfaces ; 16(24): 30728-30741, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38847598

RESUMO

The prevalence of pathogenic bacterial infections with high morbidity and mortality poses a widespread challenge to the healthcare system. Therefore, it is imperative to develop nanoformulations capable of adaptively releasing antimicrobial factors and demonstrating multimodal synergistic antimicrobial activity. Herein, an NIR-activated multifunctional synergistic antimicrobial nanospray MXene/ZIF-90@ICG was prepared by incorporating ZIF-90@ICG nanoparticles onto MXene-NH2 nanosheets. MXene/ZIF-90@ICG can on-demand release the antimicrobial factors MXenes, ICG, and Zn2+ in response to variations in pH and ATP levels within the bacterial infection microenvironment. Under NIR radiation, the combination of MXenes, Zn2+, and ICG generated a significant amount of ROS and elevated heat, thereby enhancing the antimicrobial efficacy of PDT and PTT. Meanwhile, NIR excitation could accelerate the further release of ICG and Zn2+, realizing the multimodal synergistic antibacterial effect of PDT/PTT/Zn2+. Notably, introducing MXenes improved the dispersion of the synthesized antimicrobial nanoparticles in aqueous solution, rendering MXene/ZIF-90@ICG a candidate for application as a nanospray. Importantly, MXene/ZIF-90@ICG demonstrated antimicrobial activity and accelerated wound healing in the constructed in vivo subcutaneous Staphylococcus aureus infection model with NIR activation, maintaining a favorable biosafety level. Therefore, MXene/ZIF-90@ICG holds promise as an innovative nanospray for adaptive multimodal synergistic and efficient antibacterial applications with NIR activation.


Assuntos
Trifosfato de Adenosina , Antibacterianos , Verde de Indocianina , Raios Infravermelhos , Staphylococcus aureus , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Cicatrização/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Staphylococcus aureus/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/química , Camundongos , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Nanopartículas/química , Testes de Sensibilidade Microbiana , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Escherichia coli/efeitos dos fármacos , Humanos , Fotoquimioterapia
6.
Bioorg Chem ; 148: 107423, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38733751

RESUMO

Viscosity and sulfur dioxide derivatives were significant indicators for the assessment of health threat and even cancers, therefore, on-site and real time detection of viscosity and sulfur dioxide derivatives has obtained considerable attentions. An FRET-based fluorescence probe JZX was designed and synthesized based on a novel energy donor of N,N-diethyl-4-(1H-phenanthro[9,10-d]imidazol-2-yl)benzamide fluorophore. JZX exhibited a large Stokes shift (230 nm), high energy transfer efficiency, wide emission channel gap (135 nm) and excellent stability and biocompatibility. JZX detected sulfur dioxide with low detection limit (55 nM), fast responding (16 min), high selectivity and sensitivity. Additionally, JZX tend to target endoplasmic reticulum of which normal metabolism will be disturbed by the abnormal levels of viscosity and sulfur dioxide derivatives. Prominently, JZX could concurrently detect viscosity and sulfur dioxide derivatives depending on different fluorescence signals in living cells for the screening of cancer cells. Hence, probe JZX will be a promising candidate for the detection of viscosity and sulfur dioxide derivatives, and even for the diagnosis of liver cancers.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes , Sulfitos , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Humanos , Viscosidade , Sulfitos/análise , Estrutura Molecular , Dióxido de Enxofre/análise , Imagem Óptica , Células HeLa
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 315: 124270, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38608559

RESUMO

Depression is a serious mental disease that causes grievous harm to human health and quality of life. The vesicular exocytosis of noradrenaline (NE), rather than its intrinsic intracellular concentration, is more associated with depression. Based on the reports on exocytosis of NE, it is reasonable to assume that the viscosity of cells has an important effect on the release of NE. Herein, a dual-response fluorescent probe (RHO-DCO-NE) for detecting NE and viscosity was designed and synthesized. The probe can simultaneously detect NE concentration and viscosity level with negligible crosstalk between the two channels. We utilized the probe to study the effect of viscosity changes on the NE release of PC12 and the corticosterone-induced PC12 cells. The experiment data revealed that the decrease in viscosity level can accelerate the release of NE of depression cell models. The finding provides new insight into the study of the pathological mechanisms of depression.


Assuntos
Depressão , Corantes Fluorescentes , Norepinefrina , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Células PC12 , Norepinefrina/metabolismo , Norepinefrina/análise , Viscosidade , Animais , Ratos , Depressão/tratamento farmacológico , Espectrometria de Fluorescência , Corticosterona/farmacologia
8.
J Agric Food Chem ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38624165

RESUMO

Immunochromatography (ICA) remains untapped toward enhanced sensitivity and applicability for fulfilling the nuts and bolts of on-site food safety surveillance. Herein, we report a fortified dual-spectral overlap with enhanced colorimetric/fluorescence dual-response ICA for on-site bimodal-type gentamicin (Gen) monitoring by employing polydopamine (PDA)-coated AuNPs (APDA) simultaneously serving as a colorimetric reporter and a fluorescence quencher. Availing of the enhanced colorimetric response that originated from the PDA layer, the resultant APDA exhibits less required antibody and immunoprobes in a single immunoassay, which facilitates improved antibody utilization efficiency and immuno-recognition in APDA-ICA. Further integrated with the advantageous features of fortified excitation and emission dual-spectral overlap for the Arg/ATT-AuNCs, this APDA-ICA with a "turn on/off" pattern achieves the visual limits of detection of 1.0 and 0.5 ng mL-1 for colorimetric and fluorescence patterns (25- and 50-fold lower than standard AuNPs-ICA). Moreover, the excellent self-calibration and satisfactory recovery of 79.03-118.04% were shown in the on-site visual colorimetric-fluorescence analysis for Gen in real environmental media (including real river water, an urban aquaculture water body, an aquatic product, and an animal byproduct). This work provides the feasibility of exploiting fortified dual-spectral overlap with an enhanced colorimetric/fluorescence dual response for safeguarding food safety and public health.

9.
Biofabrication ; 16(2)2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38277678

RESUMO

The inflammatory response is one of the general symptoms that accompany tumorigenesis, the pro-inflammatory factors cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandin-2 (PGE-2) in the inflammatory environment surrounding tumors possess promoting tumor development, metastasis and angiogenesis effects. In addition, the hypoxic environment of tumors severely limits the effectiveness of photodynamic therapy (PDT). In this study, a universal extracellular-intracellular 'on-demand' release nanomedicine DOX@PDA-ICG@MnO2@GN-CEL was developed for the combined fight against malignant tumors using a spatiotemporal controlled gelatin coated polydopamine (PDA@GN) as the carrier and loaded with the chemotherapeutic drug doxorubicin (DOX), the photosensitizer indocyanine green (ICG), the PDT enhancer MnO2and the anti-inflammatory drug celecoxib (CEL) individually. Our results showed that DOX@PDA-ICG@MnO2@GN-CEL could release CEL extracellularly by matrix metalloproteinase-2 response and inhibit the COX-2/PGE-2 pathway, reduce chemotherapy resistance and attenuate the concurrent inflammation. After entering the tumor cells, the remaining DOX@PDA-ICG@MnO2released DOX, ICG and MnO2intracellularly through PDA acid response. MnO2promoted the degradation of endogenous H2O2to generate oxygen under acidic conditions to alleviate the tumor hypoxic environment, enhance PDT triggered by ICG. PDA and ICG exhibited photothermal therapy synergistically, and DOX exerted chemotherapy with reduced chemotherapy resistance. The dual responsive drug release switch enabled the chemotherapeutic, photothermal, photodynamic and anti-inflammatory drugs precisely acted on different sites of tumor tissues and realized a promising multimodal combination therapy.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Humanos , Metaloproteinase 2 da Matriz , Liberação Controlada de Fármacos , Microambiente Tumoral , Ciclo-Oxigenase 2 , Compostos de Manganês , Hipertermia Induzida/métodos , Óxidos , Doxorrubicina/farmacologia , Verde de Indocianina/farmacologia , Anti-Inflamatórios , Linhagem Celular Tumoral
10.
Int J Biol Macromol ; 256(Pt 2): 127987, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37979767

RESUMO

Inflammatory bowel disease (IBD) can cause intestinal microbial imbalance and aggravate intestinal inflammation. Mixed fructan is more easily fermented by colonic microorganisms and can be used as colonic drug delivery materials. Here, we constructed a mixed fructan based nanoparticle with dual targeted stimulation of pH and intestinal flora to effectively deliver berberine for the treatment of ulcerative colitis (UC). The complex of fructan based nanoparticle and berberine (BBRNPs) significantly ameliorated the inflammatory response of sodium dextran sulfate (DSS)-induced colitis in mice by inhibiting the activation of NF-κB/STAT-3 pathway and increasing tight junction protein expression in vivo. Importantly, BBRNPs improved the responsiveness of colitis microbiome and effectively regulated the relative homeostasis of harmful flora Enterobacteriaceae and Escherichia-shigolla, and beneficial flora Ruminococcaceae and Akkermansiaceae. This study provides a promising strategy for the effective treatment of UC and expands the application of branched fructan in pharmaceutics.


Assuntos
Berberina , Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Camundongos , Animais , Berberina/farmacologia , Berberina/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colite/tratamento farmacológico , Colo , Concentração de Íons de Hidrogênio , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
11.
J Colloid Interface Sci ; 657: 1-14, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38029524

RESUMO

Nanodrug delivery systems (NDSs), such as mesoporous silica, have been widely studied because of their high specific surface area, high loading rate, and easy modification; however, they are not easily metabolized and excreted by the human body and may be potentially harmful. Hence, we aimed to examine the synergistic anti-tumor effects of ex vivo chemo-photothermal therapy to develop a rational and highly biocompatible treatment protocol for tumors. We constructed a biodegradable NDS using organic mesoporous silica with a tetrasulfide bond structure, copper sulfide core, and folic acid-modified surface (CuS@DMONs-FA-DOX-PEG) to target a tumor site, dissociate, and release the drug. The degradation ability, photothermal conversion ability, hemocompatibility, and in vitro and in vivo anti-tumor effects of the CuS@DMONs-FA-DOX-PEG nanoparticles were evaluated. Our findings revealed that the nanoparticles encapsulated in copper sulfide exhibited significant photothermal activity and optimal photothermal conversion rate. Further, the drug was accurately delivered and released into the target tumor cells, annihilating them. This study demonstrated the successful preparation, safety, and synergistic anti-tumor effects of chemo-photothermal therapeutic nanomaterials.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Humanos , Doxorrubicina , Cobre/farmacologia , Cobre/química , Terapia Fototérmica , Dióxido de Silício/química , Fototerapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanopartículas/química , Sulfetos/farmacologia , Concentração de Íons de Hidrogênio
12.
Small ; 19(52): e2304321, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37658503

RESUMO

Buildings account for ≈40% of the total energy consumption. In addition, it is challenging to control the indoor temperature in extreme weather. Therefore, energy-saving smart windows with light regulation have gained increasing attention. However, most emerging base materials for smart windows have disadvantages, including low transparency at low temperatures, ultra-high phase transition temperature, and scarce applications. Herein, a self-adaptive multi-response thermochromic hydrogel (PHC-Gel) with dual temperature and pH response is engineered through "one-pot" integration tactics. The PHC-Gel exhibits excellent mechanical, adhesion, and electrical conductivity properties. Notably, the low critical solubility temperature (LCST) of PHC-Gel can be regulated over a wide temperature range (20-35 °C). The outdoor practical testing reveals that PHC-Gel has excellent light transmittance at low temperatures and radiation cooling performances at high temperatures, indicating that PHC-Gel can be used for developing energy-saving windows. Actually, PHC-Gel-based thermochromic windows show remarkable visible light transparency (Tlum ≈ 95.2%) and solar modulation (△Tsol ≈ 57.2%). Interestingly, PHC-Gel has superior electrical conductivity, suggesting that PHC-Gel can be utilized to fabricate wearable signal-response and temperature sensors. In summary, PHC-Gel has broad application prospects in energy-saving smart windows, smart wearable sensors, temperature monitors, infant temperature detection, and thermal management.

13.
ACS Nano ; 17(17): 16553-16564, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37527488

RESUMO

Gastric cancer (GC) is one of the most common tumors worldwide and is the leading cause of tumor-related mortality. Traditional biomarkers and screening methods cannot meet the clinical demands. There is an urgent need for highly sensitive diagnostic markers as well as accurate quantification methods for early gastric cancer (EGC) screening. Here a dual-target cooperatively responsive fluorescent nanomachine by the innovative application of two targets─responsive strand migration system with a single-amplification-cycle element was developed for the simultaneous detection of GC biomarkers miR-5585-5p and PLS3 mRNA, which were selected by next-generation sequencing and RT-qPCR. It was also an RNA extraction-free, PCR-free, and nonenzymatic biosensor to achieve tumor cell imaging and serum diagnosis. Requiring only a 20 µL serum sample and 20 min incubation time, the nanomachine achieved an ultrasensitive detection limit of fM level with a broad linear range from fM to nM. More importantly, a higher AUC value (0.884) compared to the clinically used biomarker CA 72-4 was obtained by the nanomachine to distinguish GC patients successfully. Notably, for the key concerns of diagnosis of EGC patients, the nanomachine also achieved a satisfactory AUC value of 0.859. Taken together, this work has screened and obtained multiple biomarkers and developed a fluorescent nanomachine for combination diagnosis of GC, providing an ingenious design of a functionalized DNA nanomachine and a feasible strategy for the transformation of serum biomarkers into clinical diagnosis.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , DNA/genética , Corantes , Biomarcadores Tumorais , Técnicas Biossensoriais/métodos , MicroRNAs/genética
14.
Biosens Bioelectron ; 239: 115596, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37633002

RESUMO

The polarity and viscosity of the microenvironment are associated with the control of the onset and progression of pathological diseases, including inflammation, immuno-suppression and cancer. If appropriate treatment is neglected, alcoholic acute liver injury (AALI), the initial sign of alcoholic liver diseases, may transform into hepatic lesions. Therefore, it's crucial to create a particular probe to detect AALI swiftly and track its progression. Herein a polarity and viscosity dual-responsive crimson fluorescent probe (PPBI) was designed and developed, which can target mitochondria and lipid droplets. PPBI possesses aggregation-induced emission properties, good photostability and strong anti-interference ability against pH, metal ions, anions and biomolecules. This probe can distinguish cancer cells from normal ones using changes of green and red fluorescence, as well as identify changes in the cellular microenvironment associated with inflammatory and ferroptosis processes. In addition, changes in polarity and viscosity can be amplified by in vivo imaging in a mouse model to monitor alcohol-induced acute liver injury and to effectively detect the course of pharmacological intervention therapy. All the results suggest that PPBI could be a promising real-time fluorescence imaging tool for diagnosis and treatment of acute alcoholic liver injury.


Assuntos
Técnicas Biossensoriais , Corantes Fluorescentes , Animais , Camundongos , Inflamação , Microambiente Celular , Fígado
15.
ACS Appl Mater Interfaces ; 15(28): 33223-33238, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37421332

RESUMO

Intelligent stimulus-responsive theranostic systems capable of specifically sensing low-abundance tumor-related biomarkers and efficiently killing tumors remain a pressing endeavor. Here, we report a multifunctional framework nucleic acid (FNA) nanosystem for simultaneous imaging of microRNA-21 (miR-21) and combined chemo/gene therapy. To achieve this, two FNA nanoarchitectures labeled with Cy5/BHQ2 signal tags were designed, each of which contained an AS1411 aptamer, two pairs of DNA/RNA hybrids, a pH-sensitive DNA catcher, and doxorubicin (DOX) intercalating between cytosine and guanine in the tetrahedral DNA nanostructure (TDN). In the acidic tumor microenvironment, the DNA catchers spontaneously triggered to form an i-motif and create an FNA dimer (dFNA) while releasing DOX molecules to exert a cytotoxic effect. In addition, the overexpressed miR-21 in tumor cells dismantled the DNA/RNA hybrids to produce vascular endothelial growth factor-associated siRNA via a toehold-mediated strand displacement reaction, thus enabling a potent RNA interfering. Also importantly, the liberated miR-21 could initiate cascade-reaction amplification to efficiently activate the Cy5 signal reporters, thereby realizing on-site fluorescence imaging of miR-21 in living cells. The exquisitely designed FNA-based nanosystem showed favorable biocompatibility and stability as well as acid-driven DOX release characteristics. Owing to the aptamer-guided targeting delivery, specific uptake of the FNA-based theranostic nanosystem by HepG2 cells was verified with confocal laser scanning microscopy and flow cytometry analyses, which therefore resulted in apoptosis of HepG2 cells while doing minimal damage to normal H9c2 and HL-7702 cells. Strikingly, both in vitro and in vivo experiments demonstrated the achievements of the FNA-enabled miR-21 imaging and synergistically enhanced chemo/gene therapy. This work thus represents a noteworthy advance on the FNA-based theranostic strategy that can effectively avoid the undesirable premature leakage of anticarcinogen and off-target of siRNA, and achieve on-demand reagents release for tumor diagnostics and treatment.


Assuntos
MicroRNAs , Nanopartículas , Neoplasias , Ácidos Nucleicos , Humanos , MicroRNAs/genética , Medicina de Precisão , Fator A de Crescimento do Endotélio Vascular , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Doxorrubicina/farmacologia , Doxorrubicina/química , DNA , Imagem Óptica/métodos , RNA Interferente Pequeno , Nanomedicina Teranóstica , Linhagem Celular Tumoral , Microambiente Tumoral
16.
Bioorg Chem ; 138: 106603, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37210825

RESUMO

Viscosity and peroxynitrite (ONOO-) are two significant indicators to affect and evaluate the mitochondrial functional status, which are nearly relational with pathophysiological process in many diseases. Developing suitable analytical methods for monitoring mitochondrial viscosity changes and ONOO- is thus of great importance. In this research, a new mitochondria-targeted sensor DCVP-NO2 for the dual determination of viscosity and ONOO- was exploited based on the coumarin skeleton. DCVP-NO2 displayed a red fluorescence "turn-on" response toward viscosity along with about 30-fold intensity increase. Meanwhile, it could be used as ratiometric probe for detection of ONOO- with excellent sensitivity and extraordinary selectivity for ONOO- over other chemical and biological species. Moreover, thanks to its good photostability, low cytotoxicity and ideal mitochondrion-targeting capability, DCVP-NO2 was successfully utilized for fluorescence imaging of viscosity variations and ONOO- in mitochondria of living cells through different channels. In addition, the results of cell imaging revealed that ONOO- would lead to the increase of viscosity. Taken together, this work provides a potential molecular tool for researching biological functions and interactions of viscosity and ONOO- in mitochondria.


Assuntos
Corantes Fluorescentes , Ácido Peroxinitroso , Corantes Fluorescentes/química , Ácido Peroxinitroso/análise , Dióxido de Nitrogênio/análise , Viscosidade , Mitocôndrias/química
17.
J Drug Target ; 31(6): 655-669, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37235535

RESUMO

Lung metastatic breast cancer is a leading cause of cancer-related death in women and difficult to treat due to non-specific drug delivery. Herein a sequential targeting dual-responsive magnetic nanoparticle was fabricated, where Fe3O4 nanoparticle was used as magnetic core, then sequentially coated with tetraethyl orthosilicate, bis[3-(triethoxy-silyl)propyl] tetrasulfide, and 3-(trimethoxysilyl) propylmethacrylate to afford -C = C- on the surface for further polymerisation with acrylic acid, acryloyl-6-ethylenediamine-6-deoxy-ß-cyclodextrin using N, N-bisacryloylcy- stamine as cross-linker, obtaining pH/redox dual-responsive magnetic nanoparticle (MNPs-CD) to delivery doxorubicin (DOX) for suppressing lung metastatic breast cancer. Our results suggested DOX-loaded nanoparticle could target the lung metastases site by sequential targeting, in which they first be delivered to the lung and even the metastatic nodules through size-driven, electrical interaction, and magnetic field-guided mechanisms, then be effectively internalised into the cancer cells followed by intelligently triggering DOX release. MTT analysis demonstrated DOX-loaded nanoparticle exhibited high anti-tumour activity against 4T1 and A549 cells. 4T1 tumour-bearing mice were employed to confirm the higher specific accumulation in lung and improved anti-metastatic therapy efficiency of DOX by focussing an extracorporeal magnetic field on the biological target. Our findings suggested the as-proposed dual-responsive magnetic nanoparticle offered a prerequisite to inhibit lung metastasis of breast cancer tumours.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Nanopartículas de Magnetita , Nanopartículas , Feminino , Humanos , Animais , Camundongos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Pulmão , Concentração de Íons de Hidrogênio
18.
ACS Appl Mater Interfaces ; 15(20): 24175-24185, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37186879

RESUMO

Stimuli-responsive hydrogels are a class of important materials for the preparation of flexible sensors, but the development of UV/stress dual-responsive ion-conductive hydrogels with excellent tunability for wearable devices remains a major challenge. In this study, a dual-responsive multifunctional ion-conductive hydrogel (PVA-GEL-GL-Mo7) with high tensile strength, good stretchability, outstanding flexibility, and stability is successfully fabricated. The prepared hydrogel has an excellent tensile strength of 2.2 MPa, high tenacity of 5.26 MJ/m3, favorable extensibility (522%), and high transparency of 90%. Importantly, the hydrogels have dual responsiveness to UV light and stress, allowing it to be used as a wearable device while responding differently to the UV intensity of different outdoor environments (hydrogels can show different levels of color when exposed to different light intensities of UV light) and can remain flexible at -50 and 85 °C (sensing at both -25 and 85 °C). Therefore, the hydrogels developed in this study have good prospects in different applications, such as flexible wearable devices, duplicate paper, and dual-responsive interactive devices.

19.
Small ; 19(20): e2207900, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36802163

RESUMO

This work focuses on multi-stimuli-responsive materials with distinctive abilities, that is, color-changing and shape-memory. Using metallic composite yarns and polymeric/thermochromic microcapsule composite fibers, processed via a melt-spinning technique, an electrothermally multi-responsive fabric is woven. The resulting smart-fabric transfers from a predefined structure to an original shape while changing color upon heating or applying an electric field, making it appealing for advanced applications. The shape-memory and color-changing features of the fabric can be controlled by rationally controlling the micro-scale design of the individual fibers in the structure. Thus, the fibers' microstructural features are optimized to achieve excellent color-changing behavior along with shape fixity and recovery ratios of 99.95% and 79.2%, respectively. More importantly, the fabric's dual-response by electric field can be achieved by a low voltage of 5 V, which is smaller than the previously reported values. Above and beyond, the fabric is able to be meticulously activated by selectively applying a controlled voltage to any part of the fabric. The precise local responsiveness can be bestowed upon the fabric by readily controlling its macro-scale design. A biomimetic dragonfly with the shape-memory and color-changing dual-response ability is successfully fabricated, broadening the design and fabrication horizon of groundbreaking smart materials with multiple functions.

20.
Int J Biol Macromol ; 234: 123677, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36796562

RESUMO

Achyranthes plays the role of dredging the meridians and clearing the joints with a certain anti-inflammatory effect, peripheral analgesic activity and central analgesic activity. A novel self-assembled nanoparticles containing Celastrol (Cel) with matrix metalloproteinase (MMP)-sensitive chemotherapy-sonodynamic therapy was fabricated targeting macrophages at the inflammatory site of rheumatoid arthritis. Dextran sulfate (DS) with highly expressed SR-A receptor on the surface of macrophages is used to specifically target the site of inflammation; by introducing PVGLIG enzyme-sensitive polypeptides and ROS-responsive bonds, it can achieve the desired effect on MMP-2/9 and reactive oxygen species at the joint site. The preparation forms DS-PVGLIG-Cel&Abps-thioketal-Cur@Cel nanomicelles, referred to as D&A@Cel. The resulting micelles had an average size of 204.8 nm and the zeta potential -16.46 mV. The results show that activated macrophages can effectively capture Cel in in vivo experiments, indicating that Cel delivered by nanoparticles can significantly improve bioavailability.


Assuntos
Achyranthes , Artrite Reumatoide , Nanopartículas , Sistemas de Liberação de Fármacos por Nanopartículas , Artrite Reumatoide/tratamento farmacológico , Nanopartículas/química , Polissacarídeos/uso terapêutico
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