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1.
Proc Natl Acad Sci U S A ; 120(28): e2302142120, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37399399

RESUMO

Harnessing the programmable nature of DNA origami for controlling structural features in crystalline materials affords opportunities to bring crystal engineering to a remarkable level. However, the challenge of crystallizing a single type of DNA origami unit into varied structural outcomes remains, given the requirement for specific DNA designs for each targeted structure. Here, we show that crystals with distinct equilibrium phases and shapes can be realized using a single DNA origami morphology with an allosteric factor to modulate the binding coordination. As a result, origami crystals undergo phase transitions from a simple cubic lattice to a simple hexagonal (SH) lattice and eventually to a face-centered cubic (FCC) lattice. After selectively removing internal nanoparticles from DNA origami building blocks, the body-centered tetragonal and chalcopyrite lattice are derived from the SH and FCC lattices, respectively, revealing another phase transition involving crystal system conversions. The rich phase space was realized through the de novo synthesis of crystals under varying solution environments, followed by the individual characterizations of the resulting products. Such phase transitions can lead to associated transitions in the shape of the resulting products. Hexagonal prism crystals, crystals characterized by triangular facets, and twinned crystals are observed to form from SH and FCC systems, which have not previously been experimentally realized by DNA origami crystallization. These findings open a promising pathway toward accessing a rich phase space with a single type of building block and wielding other instructions as tools to develop crystalline materials with tunable properties.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , Nanopartículas Metálicas/química , Magnésio , DNA/química , Cristalização , Transição de Fase , Nanotecnologia , Conformação de Ácido Nucleico , Nanoestruturas/química
2.
J Am Chem Soc ; 146(4): 2514-2523, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38247135

RESUMO

Precise mapping and regulation of cell surface receptors hold immense significance in disease treatment, such as cancer, infection, and neurodisorders, but also face enormous challenges. In this study, we designed a series of adjustable multivalent aptamer-based DNA nanostructures to precisely control their interaction with receptors in tumor cells. By profiling surface receptors on 12 cell lines using 10 different aptamers, we generated a heatmap that accurately distinguished between various tumor types based on multiple markers. We then incorporated these aptamers onto DNA origami structures to regulate receptor recognition, with patch-like structures demonstrating a tendency to be trapped on the cell surface and with tube-like structures showing a preference for internalization. Through precise control of aptamer species, valence, and geometric patterns, we found that multiheteroreceptor-mediated recognition not only favored the specific binding of nanostructures to tumor cells but also greatly enhanced intracellular uptake by promoting clathrin-dependent endocytosis. Specifically, we achieved over 5-fold uptake in different tumor cells versus normal cells using tube-like structures modified with different diheteroaptamer pairs, facilitating targeted drug delivery. Moreover, patch-like structures with triheteroaptamers guided specific interactions between macrophages and tumor cells, leading to effective immune clearance. This programmable multivalent system allows for the precise regulation of cell recognition using multiple parameters, demonstrating great potential for personalized tumor treatment.


Assuntos
Aptâmeros de Nucleotídeos , Nanoestruturas , Neoplasias , Humanos , Aptâmeros de Nucleotídeos/química , Neoplasias/tratamento farmacológico , Nanoestruturas/química , Sistemas de Liberação de Medicamentos , DNA/química , Linhagem Celular Tumoral
3.
J Gene Med ; 26(10): e3742, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39343840

RESUMO

BACKGROUND: With its rapidly increasing incidence and prevalence, ulcerative colitis (UC) has become a major global health challenge. Recent evidence suggests that ferroptosis plays a significant role in the development of UC. However, the relationship between ferroptosis and the progression of UC needs to be extensively studied. METHODS: The differentially expressed genes in UC patients were screened from the GEO database. The ferroptosis-related genes were obtained from FErrDB and GeneCards. The UC subtypes were identified with the R package "CancerSubtype" and evaluated with consensus clustering (CC) to identify gene expression patterns in patients with UC. The key genes were detected with qRT-PCR, Western blot, and immunohistochemistry in vitro and in vivo models. Ferroptosis was identified with western blotting on ferrotic-associated proteins and staining on Fe2+ with commercial FerroOrange kits. RESULTS: Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a potential biomarker for ferroptosis in UC patients. Transcriptome sequencing data showed a positive correlation between decreased DPP4 expression and proinflammatory cytokines such as TNF-α, IL-6, and IL-ß, as well as immune cell infiltration in the colon tissues of UC patients. Furthermore, DPP4 was strongly associated with ferroptosis biomarkers, particularly in Subtype 2 of UC. Interestingly, our study also found that DPP4 expression was significantly reduced in RSL3-treated ferroptotic intestinal epithelial cells, more so than in LPS-treated cell models. Inhibition of DPP4 had a significant impact on the expression of ferroptotic biomarkers. Additionally, DPP4 expression was decreased in the colon tissues of DSS-treated mice, and the ferroptosis inhibitor Ferritin-1 effectively counteracted the effects of DSS on immune cell infiltration, colon length, and DPP4 expression. CONCLUSIONS: DPP4 can serve as a biomarker for ferroptosis in the diagnosis and management of UC.


Assuntos
Biomarcadores , Colite Ulcerativa , Dipeptidil Peptidase 4 , Ferroptose , Ferroptose/genética , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Humanos , Camundongos , Dipeptidil Peptidase 4/metabolismo , Dipeptidil Peptidase 4/genética , Animais , Citocinas/metabolismo , Perfilação da Expressão Gênica , Modelos Animais de Doenças , Masculino , Transcriptoma
4.
Chembiochem ; : e202400670, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39365708

RESUMO

Over the last four decades, research on DNA as a functional material has primarily  focused on its predictable conformation and programmable interaction. However, its low energy consumption, high responsiveness and sensitivity also make it ideal for designing specific signaling pathways, and enabling the development of molecular computers. This review mainly discusses recent advancements  in the utilization of DNA nanotechnology for molecular computer, encompassing applications in storage, cryptography and logic circuits. It elucidates the challenges encountered in the application process and presents solutions exemplified by representative works. Lastly, it delineates the challenges and opportunities within this filed.

5.
Opt Express ; 32(3): 4111-4121, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297619

RESUMO

This article presents a terahertz (THz) fast line-scanning imaging system with three-dimensional (3-D) focus-steering capability operating at 0.1 THz. The system comprises a 3-D printed rotating multi-prism plate and a dual-device structure consisting of a negative ridge pyramid and a column ridge pyramid. The simulation and experimental results demonstrate that the system generates a sheet-shaped diffraction-free beam with a projection distance of approximately 175 mm and a diffraction-free distance of approximately 200 mm. Moreover, the system maintains a resolution greater than 4 mm within the diffraction-free range. Furthermore, the proposed THz lens-less line-scanning imaging system enables 3-D scanning imaging within a set range of ±22°. The proposed approach can be extended to cover other frequencies within the THz range by appropriately adjusting the parameters. The system has the advantages of long working distance and long depth of field, making it a very attractive candidate for low-cost, easy-fabrication, and easy-adjustment solutions for the next generation of THz fast detection and imaging technology.

6.
J Org Chem ; 89(12): 9118-9124, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38842393

RESUMO

The first regio- and stereoselective difluoroalkylthiocyanation of alkynes with BrCF2R and KSCN has been disclosed under visible light-induced copper catalysis. The copper complex photosensitizer formed in situ not only promotes the generation of CF2-alkyl radicals but also facilitates the construction of C-SCN bonds, allowing the reaction to proceed smoothly without any additional photocatalysts or radical initiators. Moreover, the challenging internal alkynes can also be transformed to deliver CF2-derived tetrasubstituted olefins with potential applications in agricultural and medicinal chemistry.

7.
Biometals ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713412

RESUMO

Inflammatory bowel disease (IBD) is a non-specific chronic inflammatory disorder of the gastrointestinal tract, imposing significant burdens on both society and individuals. As a new type of regulated cell death (RCD), ferroptosis is different from classic RCDs such as apoptosis and necrosis in cell morphology, biochemistry and genetics. The main molecular mechanisms of ferroptosis include dysregulation of iron metabolism, impaired antioxidant capacity, mitochondrial dysfunction, accumulation of lipid-associated super-oxides, and membrane disruption. In recent years, increasing evidence has shown that ferroptosis is involved in the pathophysiology of inflammatory bowel disease. However, the exact roles and underlying molecular mechanisms have not been fully elucidated. This article reviews the mechanism of ferroptosis in the occurrence and development of inflammatory bowel disease, in order to provide new ideas for the pathophysiological research of inflammatory bowel disease. Additionally, we discuss potential strategies for the prevention and treatment of inflammatory bowel disease by targeting ferroptosis.

8.
Opt Express ; 31(17): 27407-27419, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710817

RESUMO

In this paper, various hollow structured optical fields are generated by skillfully adjusting the number and positions of multiple off-axis vortices loaded in a Gaussian beam. The focal-field characteristics of the generated hollow structured optical fields after passing through an ordinary lens are studied based on the scalar diffraction theory. Firstly, a variety of hollow structured optical fields are theoretically simulated by adjusting the number and positions of multiple off-axis vortices loaded in the Gaussian beam. The focal-field characteristics of the hollow structured optical fields after passing through a lens are theoretically analyzed. On this basis, the experiments are implemented in the built optical system for multi-off-axis vortex beam focusing through an ordinary lens. In the experiments, various hollow structured optical fields are detected in CCD which are consistent with the theoretical results. The manipulations of size and rotation direction of the hollow structured optical fields are realized. We believe that this study will contribute to extending the potential applications of off-axis vortex beams in fields such as optical field shaping, optical manipulation and laser processing.

9.
Appl Opt ; 62(7): 1654-1661, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37132909

RESUMO

A method to use a pulsed solid-state laser to create structural color modulation on metal-coated colloidal crystal surfaces by changing the scanning speed has been proposed. Vivid colors as cyan, orange, yellow, and magenta are obtained with different predefined stringent geometrical and structural parameters. The effect of laser scanning speeds and polystyrene (PS) particle sizes on the optical properties is studied, and the angle-dependent property of the samples is also discussed. As a result, the reflectance peak is progressively red shifted along with increasing the scanning speed from 4 mm/s to 200 mm/s with 300 nm PS microspheres. Moreover, the influence of the microsphere particle sizes and incident angle are also experimentally investigated. For 420 and 600 nm PS colloidal crystals, along with a gradual decrease in the scanning speed of the laser pulse from 100 mm/s to 10 mm/s and an increase in the incident angle from 15° to 45°, there was a blue shift for two reflection peak positions. This research is a key, low-cost step toward applications in green printing, anti-counterfeiting, and other related fields.

10.
Medicina (Kaunas) ; 59(2)2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36837392

RESUMO

Background and Objectives: Sevoflurane is a commonly used inhalational anaesthetic in clinics. Prolonged exposure to sevoflurane can induce significant changes in lipid metabolism and neuronal damage in the developing brain. However, the effect of exposure of pregnant rats to clinical doses of sevoflurane remains unclear. Materials and Methods: Twenty-eight pregnant rats were randomly and equally divided into sevoflurane exposure (S) group, control (C) and a blank group at gestational day (G) 18; Rats in S group received 2% sevoflurane with 98% oxygen for 6 h in an anesthetizing chamber, while C group received 100% oxygen at an identical flow rate for 6 h in an identical chamber. Partial least squares discriminant analysis (PLS-DA), ultra performance liquid chromatography/time-of-flight mass spectrometry(UPLC/TOF-MS) and MetaboAnalyst were used to analysis acquire metabolomics profiles, and immunohistochemical changes of neuronalapoptosis in hippocampus and cortex of neonatal rats were also analyzed. Results: This study aimed to explore lipidomics and transcriptomics changes related to 2% sevoflurane exposure for 6 h in the developing brains of newborn offspring rats. Ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) and RNA sequencing (RNA-seq) analyses were used to acquire metabolomics and transcriptomics profiles. We used RNA-seq to analyse the expression of the coding and non-coding transcripts in neural cells of the cerebral cortex. No significant differences in arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), or arterial blood gas were found between the groups. The relative standard deviation (RSD) of retention times was <1.53%, and the RSDs of peak areas ranged from 2.13% to 8.51%. Base peak chromatogram (BPC) profiles showed no differences between the groups. We evaluated the partial least square-discriminant analysis (PLS-DA) model. In negative ion mode, R2X was over 70%, R2Y was over 93%, and Q2 (cum) was over 80%. Cell apoptosis was not remarkably enhanced by TUNEL and haematoxylin and eosin (HE) staining in the sevoflurane-exposed group compared to the control group (p > 0.05). Glycerophospholipid (GP) and sphingolipid metabolism disturbances might adversely influence neurodevelopment in offspring. The expression of mRNAs (Vcan gene, related to neuronal development, function and repair) of the sevoflurane group was significantly increased in the differential genes by qRT-PCR verification. Conclusions: GP and sphingolipid metabolism homeostasis may be potential therapeutic approaches against inhalational anaesthetic-induced neurodegenerative disorders. Meanwhile, sevoflurane-induced Vcan changes indicated some lipidomic and transcriptomic changes, even if neural cell apoptosis was not significantly changed in the usual clinical dose of sevoflurane exposure.


Assuntos
Anestésicos Inalatórios , Sevoflurano , Animais , Feminino , Gravidez , Ratos , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/efeitos adversos , Oxigênio , Sevoflurano/administração & dosagem , Sevoflurano/efeitos adversos , Esfingolipídeos
11.
J Opt Soc Am A Opt Image Sci Vis ; 39(5): 916-926, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36215453

RESUMO

In order to study the influence and mechanisms of color differences using 3D-shaped objects, 440 pairs of 3D samples surrounding five CIE color centers (gray, red, yellow, green, and blue) with the variations of gloss, size, and shape were prepared by a Sailner 3D color printer, and their color differences were assessed by 26∼45 observers using the gray-scale method. The new color difference data were used to investigate the parametric effects (gloss, 3D shape, and size) on the perceived color difference. Results indicate that, for 3D objects, high gloss and small size objects (2 cm) raise smaller visual color differences than matte and large size objects (4 cm), and the visual color difference of spheres is larger than that of the cone and cylinder sample pairs. The chromaticity ellipses indicated that the glossy samples with different shapes will arouse fairly different visual perceptions, especially for sphere and cylinder samples.


Assuntos
Percepção de Forma , Cor , Percepção de Cores , Iluminação , Impressão Tridimensional , Propriedades de Superfície
12.
Analyst ; 146(6): 1807-1819, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33595553

RESUMO

Due to the proposal and evolution of the DNA origami technique over the past decade, DNA molecules have been utilized as building blocks for the precise construction of nanoscale architectures. Benefiting from the superior programmability of DNA molecules, the sequence-dependent recognition mechanism and robust complementation among DNA strands make it possible to customize almost arbitrary structures. Such an assembly strategy bypasses some of the limits of conventional fabrication methods; the fabrication accuracy and complexity of the target product are unprecedentedly promoted as well. Furthermore, due to the spatial addressability of the final products, nanostructures assembled through the DNA origami technique can also serve as a versatile platform for the spatial positioning of functional elements, represented by colloidal nanoparticles (NPs). The subsequent fabrication of heterogeneous functional nanoarchitectures is realized via modifying colloidal NPs with DNA strands and manipulating them to anchor into DNA origami templates. This has given rise to investigations of their novel properties in nanophotonics and therapeutic effects towards some diseases. In this review, we survey the crucial progress in the development of DNA origami design, assembly and structural analysis and summarize available applications in nanophotonics and cancer therapy based on the object-dressed DNA origami complex. Moreover, we elucidate the development of this field and discuss the potential directions of this kind of application-oriented nanomanufacturing.


Assuntos
Nanopartículas , Nanoestruturas , Neoplasias , DNA , Humanos , Nanotecnologia , Neoplasias/tratamento farmacológico , Conformação de Ácido Nucleico
13.
Opt Express ; 28(11): 16298-16308, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32549455

RESUMO

The d1-d2-d3-d4-d5 gradient-type spoof surface plasmons (SSP) grating was designed and found to exert an obvious effect on electric field localization. Two gradient-shaped planar ports were added to the bottom of this grating to form a gradient-type slotted SSP grating and achieve tight focusing and local electric field enhancement for a terahertz wave. The size of the focal spot was optimized to 0.01λ. The single-gradient-type slotted SSP grating was considered as a unit and arranged in one and two dimensions to generate a longitudinal focal line and square focal spots array. This did not only improve the resolution of terahertz imaging, but also simultaneously scan multiple focal spots to increase the speed of terahertz imaging. This work makes the manipulation of terahertz wave more flexible and efficient which has great potential in terahertz high-resolution near-field scanning imaging.

15.
Analyst ; 143(19): 4655-4661, 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30168539

RESUMO

A fluorescent and colorimetric anion sensor based on the activated C-H group has been developed, and its reusability and ability to selectively detect cyanides have been demonstrated. The system utilizes trifluoromethylcarbinol-directed C-H regioselective cyanomethylation for direct C-C bond formation between the fluorophore and acetonitrile. The present paper also describes a novel strategy for the enhancement of carbanion stability by a potential intramolecular C[double bond, length as m-dash]OH-C hydrogen bonding system, thus providing a new way to develop activated CH-based anion receptors.

16.
BMC Anesthesiol ; 17(1): 79, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28619016

RESUMO

BACKGROUND: Awake fiberoptic bronchoscopic tracheal intubation is usually regarded as an effective method in the management of predicted difficult airway. Hypoxia during awake nasal fiberoptic bronchoscopic intubation leads to discontinuation of the procedure, prolonged manipulation time and increased risk of severe complications. The main aim of the study was to test whether the novel endoscopic mask is helpful for hypoxia during the intubation. METHODS: This was a randomized, controlled, multi-center study. 55 patients were recruited, but one patient was lost to follow-up. Finally, 54 patients (19 man and 35 women) were analyzed. After entering the operating room, nasal catheter oxygen-providing was given in the control group, and the treatment group received endoscopic mask oxygen-providing, with a flow rate of 3 L/min, lasting into the end of the intubation. Primary outcomes included mean arterial pressure, heart rate, minimum pulse oxygen saturation and incidence of pulse oxygen saturation ≤ 90%. Secondary outcomes included number of intubation attempts and time to intubation. All outcomes were finally measured. RESULTS: Minimum pulse oxygen saturation during awake nasal fiberoptic bronchoscopic tracheal intubation was significantly higher in the endoscopic mask intubation group (91.7% ± 4.7%) than that the nasal catheter intubation group (87.6% ± 8.2%, P = 0.031. Furthermore, the incidence of pulse oxygen saturation ≤ 90% was significantly lower in the endoscopic mask intubation group (20.0%, 5/25) than that in the nasal catheter intubation group (51.7%, 15/29, P = 0.037). But mean arterial pressure of during intubation was significantly higher in the endoscopic mask group (100.0 ± 13.3 vs 90.3 ± 21.8, P = 0.049). In addition, there were no differences in the number of intubation attempts (P = 0.45) or time to intubation between the two groups (P = 0.38). CONCLUSIONS: The endoscopic mask was safely used in awake fiberoptic bronchoscopic tracheal intubation, with advantages of stable blood pressure and potential prevention of desaturation. Beginners for the intubation procedure and patients at high risk of hypoxia could benefit from the use of the endoscopic mask. TRIAL REGISTRATION: Trial registration: www.chictr.org.cn . Registration No.: ChiCTR-TRC-13004086. Date of Registration: 8th, Sep, 2013.


Assuntos
Broncoscopia , Intubação Intratraqueal/instrumentação , Pressão Sanguínea , Desenho de Equipamento , Feminino , Tecnologia de Fibra Óptica , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria
17.
Med Sci Monit ; 21: 1843-9, 2015 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-26111971

RESUMO

BACKGROUND: The aim of this study was to compare the novel needle-over-cannula vs. the Braun continuous peripheral nerve block catheter set (Contiplex A) in postoperative analgesics after total knee arthroplasty (TKA). MATERIAL AND METHODS: Sixty patients undergoing total knee arthroplasty were randomly assigned to Braun continuous peripheral nerve block catheter set group (Braun Group, n=30) or the novel needle-over-cannula group (Cannula Group, n=30). All the patients in the 2 groups received continuous femoral nerve block (CFNB) for postoperative analgesics. RESULTS: We found no significant difference in analgesic effect between the 2 groups. The time of catheter or cannula insertion was shorter in the Cannula Group than in the Braun Group. Four (13.32%) out of 30 patients had failed catheter insertions in the Braun Group compared to none in the Cannula Group. Twelve (46%) out of 26 patients in the Braun Group had serious local anesthetic leakage at puncture sites during 12 h compared to none in the Cannula Group. CONCLUSIONS: The novel needle-over-cannula is effective, convenient, and safe in CFNB after TKA.


Assuntos
Analgésicos/administração & dosagem , Artroplastia do Joelho , Catéteres , Nervo Femoral/efeitos dos fármacos , Agulhas , Bloqueio Nervoso/métodos , Cuidados Pós-Operatórios , Humanos , Método Simples-Cego
18.
Infect Drug Resist ; 16: 4729-4740, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37492797

RESUMO

Background: To evaluate the risk factors and prognosis of patients with acute cholangitis recurrence. Methods: A total of 503 patients with acute cholangitis admitted to the First Affiliated Hospital of Chongqing Medical University between July 2013 and January 2022 were included in this retrospective observational study, who were followed up for 360 days and divided into relapse group and non-recurrence group according to the recurrence of acute cholangitis. Risk factors and prognosis of patients with acute cholangitis recurrence were analyzed by univariate, multivariate analyses and proportional hazards model. Results: A total of 161 patients with recurrent acute cholangitis were identified. Recurrent acute cholangitis usually occurred within 125 days; Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis, and Enterococcus faecium was the most common positive record both in blood and bile culture. In the multivariate analysis, abdominal pain (OR = 2.448, 95% CI = 1.196-5.010, P = 0.014), bile stones (OR = 2.429, 95% CI = 1.024-5.762, P = 0.044), diabetes (OR = 1.790, 95% CI = 1.007-3.182, P = 0.047), pathogen (OR = 3.305, 95% CI = 1.932-5.654, P<0.001), and chronic kidney disease (OR = 2.500, 95% CI = 1.197-5.221, P = 0.015) may be ascertained as the risk factors of acute cholangitis recurrence. The recurrence of acute cholangitis was identified as an independent risk factor for patient death (HR = 4.524, 95% CI = 1.426-14.357, P = 0.010) by Cox proportional-hazards regression. Conclusion: Abdominal pain, bile stones, diabetes and chronic kidney disease may be risk factors of acute cholangitis recurrence. Patients with recurrent acute cholangitis have poor prognosis and high mortality. Early control of recurrent risk factors and active intervention are beneficial to high-risk patients.

19.
J Mater Chem B ; 11(27): 6404-6411, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37338519

RESUMO

Designing a multifunctional nanoplatform that combines multiple treatments has emerged as an innovative cancer treatment strategy. A simple and clear route is put forward to develop Cu2+-doped zinc phosphate coated prussian blue nanoparticles (designated as PB@Cu2+/ZnP NPs) integrating tri-modal therapy (chemo, chemodynamic and photothermal therapy) for maximizing anti-tumor efficacy. The obtained PB@Cu2+/ZnP NPs possess drug loading capacity due to the mesoporous structure present in the Cu2+-doped ZnP shell. In addition, the Cu2+-doped ZnP shell can gradually degrade in response to the mildly acidic tumor microenvironment to release DOX and Cu2+, where the released drug plays the role of chemotherapy agent and the Cu2+ can react with intracellular glutathione to achieve a Cu-mediated Fenton-like reaction for chemodynamic therapy. Moreover, under laser irradiation, the heat garnered by the photothermal conversion of PB can be applied for photothermal therapy and enhance the generation of toxic ˙OH as well as the amount of DOX released, further boosting chemo- and chemodynamic therapy to realize a combined therapy. Importantly, the PB@Cu2+/ZnP NPs effectively limit the growth of tumors via the coordinated action of chemo/chemodynamic/photothermal therapy and no noticeable systematic toxicity can be found in mice. Taken together, the PB@Cu2+/ZnP NPs can act as a prospective therapeutic nanoplatform for multi-modal therapy of tumors.


Assuntos
Nanocompostos , Neoplasias , Animais , Camundongos , Doxorrubicina/farmacologia , Doxorrubicina/química , Terapia Fototérmica , Fototerapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Microambiente Tumoral
20.
Cells ; 11(11)2022 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-35681475

RESUMO

Colorectal cancer (CRC) is the third most common cancer worldwide, and its incidence and mortality rates have been increasing annually in recent years. A variety of different small extracellular vesicles (sEVs) are important mediators of intercellular communication and have an important role in tumor metastasis and progression. The development and metastasis of CRC are closely linked to tumor-cell-derived sEVs, non-tumor-cell-derived sEVs, and intestinal-microbiota-derived sEVs. Numerous studies have shown that the tumor microenvironment (TME) is a key component in the regulation of CRC proliferation, development, and metastasis. These sEVs can create a TME conducive to CRC growth and metastasis by forming an immunosuppressive microenvironment, remodeling the extracellular matrix, and promoting tumor cell metabolism. Therefore, in this paper, we review the role of different types of sEVs in colorectal cancer development and metastasis. Furthermore, based on the properties of sEVs, we further discuss the use of sEVs as early biomarkers for colorectal cancer diagnosis and the potential for their use in the treatment of CRC.


Assuntos
Neoplasias Colorretais , Vesículas Extracelulares , Comunicação Celular , Neoplasias Colorretais/patologia , Vesículas Extracelulares/metabolismo , Humanos , Microambiente Tumoral
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