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1.
ACS Nano ; 18(24): 15590-15606, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38847586

RESUMEN

To date, long-term and continuous ultrasonic imaging for guiding the puncture biopsy remains a challenge. In order to address this issue, a multimodality imaging and therapeutic method was developed in the present study to facilitate long-term ultrasonic and fluorescence imaging-guided precision diagnosis and combined therapy of tumors. In this regard, certain types of photoactivated gas-generating nanocontrast agents (PGNAs), capable of exhibiting both ultrasonic and fluorescence imaging ability along with photothermal and sonodynamic function, were designed and fabricated. The advantages of these fabricated PGNAs were then utilized against tumors in vivo, and high therapeutic efficacy was achieved through long-term ultrasonic imaging-guided treatment. In particular, the as-prepared multifunctional PGNAs were applied successfully for the fluorescence-based determination of patient tumor samples collected through puncture biopsy in clinics, and superior performance was observed compared to the clinically used SonoVue contrast agents that are incapable of specifically distinguishing the tumor in ex vivo tissues.


Asunto(s)
Medios de Contraste , Ultrasonografía , Medios de Contraste/química , Medios de Contraste/farmacología , Humanos , Animales , Ratones , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/terapia , Imagen Óptica , Gases/química , Línea Celular Tumoral , Femenino , Ratones Desnudos
2.
Anal Chem ; 96(23): 9684-9692, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38804540

RESUMEN

Herein, we report a DNA origami plasmonic nanoantenna for the programmable surface-enhanced Raman scattering (SERS) detection of cytokine release syndrome (CRS)-associated cytokines (e.g., tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)) in cancer immunotherapy. Typically, the nanoantenna was made of self-assembled DNA origami nanotubes (diameter: ∼19 nm; length: ∼90 nm) attached to a silver nanoparticle-modified silicon wafer (AgNP/Si). Each DNA origami nanotube contains one miniature gold nanorod (AuNR) inside (e.g., length: ∼35 nm; width: ∼7 nm). Intriguingly, TNF-α and IFN-γ logically regulate the opening of the nanotubes and the dissociation of the AuNRs from the origami structure upon binding to their corresponding aptamers. On this basis, we constructed a complete set of Boolean logic gates that read cytokine molecules as inputs and return changes in Raman signals as outputs. Significantly, we demonstrated that the presented system enables the quantification of TNF-α and IFN-γ in the serum of tumor-bearing mice receiving different types of immunotherapies (e.g., PD1/PD-L1 complex inhibitors and STING agonists). The sensing results are consistent with those of the ELISA. This strategy fills a gap in the use of DNA origami for the detection of multiple cytokines in real systems.


Asunto(s)
Técnicas Biosensibles , Citocinas , ADN , Oro , Inmunoterapia , Nanopartículas del Metal , Espectrometría Raman , Animales , Ratones , ADN/química , Citocinas/metabolismo , Citocinas/sangre , Oro/química , Nanopartículas del Metal/química , Humanos , Plata/química , Nanotubos/química , Neoplasias , Interferón gamma/sangre , Interferón gamma/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangre
3.
Adv Healthc Mater ; 13(16): e2303474, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38458151

RESUMEN

Electrotherapy is of great interest in the field of tissue repair as an effective, well-tolerated, and noninvasive treatment. Triboelectric nanogenerator (TENG) has shown advantages in promoting wound healing due to its peak output characteristic and low Joule heating effect. However, it is limited in infected wound healing due to poor antimicrobial capacity. Here, a wearable triboelectric stimulator (WTS) is developed that consists of a flexible TENG (F-TENG) and a triboelectric-responsive drug delivery hydrogel (TR-DDH) for healing of bacterium-infected wounds. F-TENG can generate pulsed current to wounds by converting mechanical energy from body movements. Polypyrrole is prone to reduction and volume contraction under electrical stimulation, resulting in desorption of curcumin nanoparticles (CUR NPs) from the polypyrrole in TR-DDH. Therefore, the highly efficient and controllable release of CUR NPs can be achieved by triboelectric stimulation. According to the in vitro and in vivo experiments, WTS has the greatest antimicrobial effect and the fastest promotion of infected wound healing compared to treatment with electrical stimulation or curcumin. Finally, the safety assessment demonstrates that the WTS has excellent tissue safety for chronic wound healing. Synergistic therapy with WTS provides an efficient strategy for chronic wound healing and smart-responsive drug delivery systems.


Asunto(s)
Curcumina , Sistemas de Liberación de Medicamentos , Hidrogeles , Pirroles , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Curcumina/química , Curcumina/farmacología , Hidrogeles/química , Animales , Sistemas de Liberación de Medicamentos/métodos , Pirroles/química , Polímeros/química , Nanopartículas/química , Ratones , Terapia por Estimulación Eléctrica/métodos , Dispositivos Electrónicos Vestibles , Humanos , Antibacterianos/química , Antibacterianos/farmacología , Masculino
4.
Adv Mater ; 36(26): e2400622, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38489844

RESUMEN

Existing tear sensors are difficult to perform multiplexed assays due to the minute amounts of biomolecules in tears and the tiny volume of tears. Herein, the authors leverage DNA tetrahedral frameworks (DTFs) modified on the wireless portable electrodes to effectively capture 3D hybridization chain reaction (HCR) amplifiers for automatic and sensitive monitoring of multiple cytokines in human tears. The developed sensors allow the sensitive determination of various dry eye syndrome (DES)-associated cytokines in human tears with the limit of detection down to 0.1 pg mL-1, consuming as little as 3 mL of tear fluid. Double-blind testing of clinical DES samples using the developed sensor and commercial ELISA shows no significant difference between them. Compared with single-biomarker diagnosis, the diagnostic accuracy of this sensor based on multiple biomarkers has improved by ≈16%. The developed system offers the potential for tear sensors to enable personalized and accurate diagnosis of various ocular diseases.


Asunto(s)
Técnicas Biosensibles , Citocinas , Síndromes de Ojo Seco , Hibridación de Ácido Nucleico , Lágrimas , Humanos , Lágrimas/química , Citocinas/análisis , Citocinas/metabolismo , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/metabolismo , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , ADN/química , ADN/análisis , Límite de Detección , Electrodos , Biomarcadores/análisis
5.
Chem Sci ; 15(9): 3262-3272, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38425519

RESUMEN

The precisely engineered structures of materials greatly influence the manifestation of their properties. For example, in the process of alkali metal ion storage, a carefully designed structure capable of accommodating inserted and extracted ions will improve the stability of material cycling. The present study explores the uniform distribution of self-grown carbon nanotubes to provide structural support for the conductive and elastic MXene layers of Ti3C2Tx-Co@NCNTs. Furthermore, a compatible electrolyte system has been optimized by analyzing the solvation structure and carefully regulating the component in the solid electrolyte interphase (SEI) layer. Mechanistic studies demonstrate that the decomposition predominantly controlled by FSI- leads to the formation of a robust inorganic SEI layer enriched with KF, thus effectively inhibiting irreversible side reactions and major structural deterioration. Confirming our expectations, Ti3C2Tx-Co@NCNTs exhibits an impressive reversible capacity of 260 mA h g-1, even after 2000 cycles at 500 mA g-1 in 1 M KFSI (DME), surpassing most MXene-based anodes reported for PIBs. Additionally, density functional theory (DFT) calculations verify the superior electronic conductivity and lower K+ diffusion energy barriers of the novel superstructure of Ti3C2Tx-Co@NCNTs, thereby affirming the improved electrochemical kinetics. This study presents systematic evaluation methodologies for future research on MXene-based anodes in PIBs.

6.
ACS Nano ; 17(21): 21262-21273, 2023 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-37870459

RESUMEN

Enzyme mimics (EMs) with intrinsic catalysis activity have attracted enormous interest in biomedicine. However, there is a lack of environmentally adaptive EMs for sensitive diagnosis and specific catalytic therapeutics in simultaneous manners. Herein, the coordination modulation strategy is designed to synthesize silicon-based phosphorescence enzyme-mimics (SiPEMs). Specifically, the atomic-level engineered Co-N4 structure in SiPEMs enables the environment-adaptive peroxidase, oxidase, and catalase-like activities. More intriguingly, the internal Si-O networks are able to stabilize the triplet state, exhibiting long-lived phosphorescence with lifetime of 124.5 ms, suitable for millisecond-range time-resolved imaging of tumor cells and tissue in mice (with high signal-to-background ratio values of ∼60.2 for in vitro and ∼611 for in vivo). Meanwhile, the SiPEMs act as an oxidative stress amplifier, allowing the production of ·OH via cascade reactions triggered by the tumor microenvironment (∼136-fold enhancement in peroxidase catalytic efficiency); while the enzyme-mimics can scavenge the accumulation of reactive oxygen species to alleviate the oxidative damage in normal cells, they are therefore suitable for environment-adaptive catalytic treatment of cancer in specific manners. We innovate a systematic strategy to develop high-performance enzymemics, constructing a promising breakthrough for replacing traditional enzymes in cancer treatment applications.


Asunto(s)
Peroxidasa , Peroxidasas , Animales , Ratones , Catálisis , Especies Reactivas de Oxígeno , Estrés Oxidativo
7.
iScience ; 26(10): 107821, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37731613

RESUMEN

Current gaseous sensors hardly discriminate trace volatile organic compounds at the ppt level. Herein, we present an integrated platform for simultaneously enabling rapid preconcentration, reliable surface-enhanced Raman scattering, (SERS) detection and automatic identification of trace aldehydes at the ppt level. For rapid preconcentration, we demonstrate that the nozzle-like microfluidic concentrator allows the enrichment of rare gaseous analytes by five-fold in only 0.01 ms. The enriched gas is subsequently captured and detected by an integrated silicon-based SERS chip, which is made of zeolitic imidazolate framework-8 coated silver nanoparticles grown in situ on a silicon wafer. After SERS measurement, a fully connected deep neural network is built to extract faint features in the spectral dataset and discriminate volatile organic compound classes. We demonstrate that six kinds of gaseous aldehydes at 100 ppt could be detected and classified with an identification accuracy of ∼80.9% by using this platform.

8.
Nano Lett ; 23(10): 4326-4333, 2023 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-37130058

RESUMEN

Escherichia coli K1 (EC-K1) can bypass the blood-brain barrier (BBB) and cause meningitis. Excitingly, we find the "dead EC-K1" can safely penetrate the BBB because they retain the intact structure and chemotaxis of the live EC-K1, while losing their pathogenicity. Based on this, we develop a safe "dead EC-K1"-based drug delivery system, in which EC-K1 engulf the maltodextrin (MD)-modified therapeutics through the bacteria-specific MD transporter pathway, followed by the inactivation via UV irradiation. We demonstrate that the dead bacteria could carry therapeutics (e.g., indocyanine green (ICG)) and together bypass the BBB after intravenous injection into the mice, delivering ∼3.0-fold higher doses into the brain than free ICG under the same conditions. What is more, all mice remain healthy even after 14 days of intravenous injection of ∼109 CFU of inactive bacteria. As a proof of concept, we demonstrate the developed strategy enables the therapy of bacterial meningitis and glioblastoma in mice.


Asunto(s)
Barrera Hematoencefálica , Meningitis Bacterianas , Animales , Ratones , Escherichia coli , Encéfalo , Meningitis Bacterianas/microbiología , Virulencia
9.
Sci Total Environ ; 892: 163867, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37201820

RESUMEN

Artificial sweeteners (ASs) are emerging contaminants in the environment, primarily derived from wastewater treatment plant (WWTP) effluents. In this study, the influents and effluents of three WWTPs in the Dalian urban area, China, were analyzed for the distribution of 8 typical ASs to investigate their seasonal fluctuations in the WWTPs. The results showed that acesulfame (ACE), sucralose (SUC), cyclamate (CYC), and saccharin (SAC) were both detected in the influent and effluent water samples of WWTPs, with concentrations ranging from not detected (ND) to 14.02 µg·L-1. In addition, SUC was the most abundant ASs type, accounting for 40 %-49 % and 78 %-96 % of the total ASs in the influent and effluent water, respectively. The WWTPs revealed high removal efficiencies of CYC, SAC, and ACE, while the SUC removal efficiency was poor (26 % ± 36 %). The ACE and SUC concentrations were higher in spring and summer, and all ASs showed lower levels in winter, which may be caused by the high consumption of ice-cream in warmer months. The per capita ASs loads in the WWTPs were determined in this study based on the wastewater analysis results. The calculated per capita daily mas loads for individual ASs ranged from 0.45 g·d-1·1000p-1 (ACE) to 2.04 g·d-1·1000p-1 (SUC). In addition, the relationship between per capita ASs consumption and socioeconomic status showed no significant correlation.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , China , Ciclamatos/análisis , Monitoreo del Ambiente , Sacarina/análisis , Edulcorantes/análisis , Agua/análisis , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos
10.
Angew Chem Int Ed Engl ; 62(29): e202303997, 2023 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-37148489

RESUMEN

We report the "water-in-oil-in-water" preparation of kidney injury molecule-1-targeting supramolecular chemiluminescence (CL) reporters (PCCS), consisting of L-serine-modified poly(lactic-co-glycolic) acid (PLGA)-encapsulated peroxyoxalate (CPPO), chlorin e6 (Ce6) and superoxide dismutase (SOD), for early diagnosis and amelioration of acute kidney injury (AKI). In this system, O2 ⋅- , a biomarker of AKI, triggers the oxidation of CPPO to 1,2-dioxetanedione and subsequent CL emission via CL resonance energy transfer to Ce6. The L-serine-modified PLGA stabilizes CPPO and Ce6 via noncovalent interactions, promoting long-lived CL (half-lives: ≈1000 s). Transcriptomics analysis shows that PCCS reporters reduce the inflammatory response through glutathione metabolism and inhibition of the tumor necrosis factor signaling pathway. The reporters are able to non-invasively detect AKI at least 12 h earlier than current assays, and their antioxidant properties allow simultaneous treatment of AKI.


Asunto(s)
Lesión Renal Aguda , Superóxidos , Humanos , Luminiscencia , Superóxido Dismutasa/metabolismo , Lesión Renal Aguda/diagnóstico , Ácido Láctico , Diagnóstico Precoz , Agua
11.
ACS Nano ; 17(8): 7750-7764, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37022677

RESUMEN

Optogenetic therapy has emerged as a promising technique for the treatment of ocular diseases; however, most optogenetic tools rely on external blue light to activate the photoswitch, whose relatively strong phototoxicity may induce retinal damage. Herein, we present the demonstration of camouflage nanoparticle-based vectors for in situ bioluminescence-driven optogenetic therapy of retinoblastoma. In biomimetic vectors, the photoreceptor CRY2 and its interacting partner CIB1 plasmid are camouflaged with folic acid ligands and luciferase NanoLuc-modified macrophage membranes. To conduct proof-of-concept research, this study employs a mouse model of retinoblastoma. In comparison to external blue light irradiation, the developed system enables an in situ bioluminescence-activated apoptotic pathway to inhibit tumor growth with greater therapeutic efficacy, resulting in a significant reduction in ocular tumor size. Furthermore, unlike external blue light irradiation, which causes retinal damage and corneal neovascularization, the camouflage nanoparticle-based optogenetic system maintains retinal structural integrity while avoiding corneal neovascularization.


Asunto(s)
Neovascularización de la Córnea , Nanopartículas , Neoplasias de la Retina , Retinoblastoma , Animales , Ratones , Optogenética/métodos
12.
Nat Commun ; 14(1): 2331, 2023 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-37087540

RESUMEN

Most existing bioluminescence imaging methods can only visualize the location of engineered bacteria in vivo, generally precluding the imaging of natural bacteria. Herein, we leverage bacteria-specific ATP-binding cassette sugar transporters to internalize luciferase and luciferin by hitchhiking them on the unique carbon source of bacteria. Typically, the synthesized bioluminescent probes are made of glucose polymer (GP), luciferase, Cy5 and ICG-modified silicon nanoparticles and their substrates are made of GP and D-luciferin-modified silicon nanoparticles. Compared with bacteria with mutations in transporters, which hardly internalize the probes in vitro (i.e., ~2% of uptake rate), various bacteria could robustly engulf the probes with a high uptake rate of around 50%. Notably, the developed strategy enables ex vivo bioluminescence imaging of human vitreous containing ten species of pathogens collected from patients with bacterial endophthalmitis. By using this platform, we further differentiate bacterial and non-bacterial nephritis and colitis in mice, while their chemiluminescent counterparts are unable to distinguish them.


Asunto(s)
Transportadoras de Casetes de Unión a ATP , Azúcares , Humanos , Ratones , Animales , Transportadoras de Casetes de Unión a ATP/genética , Silicio , Luciferasas/metabolismo , Adenosina Trifosfato , Mediciones Luminiscentes/métodos
13.
Adv Mater ; 35(28): e2300477, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37002615

RESUMEN

Current vehicles used to deliver antisense oligonucleotides (ASOs) cannot distinguish between bacterial and mammalian cells, greatly hindering the preclinical or clinical treatment of bacterial infections, especially those caused by antibiotic-resistant bacteria. Herein, bacteria-specific ATP-binding cassette (ABC) sugar transporters are leveraged to selectively internalize ASOs by hitchhiking them on α (1-4)-glucosidically linked glucose polymers. Compared with their cell-penetrating peptide counterparts, which are non-specifically engulfed by mammalian and bacterial cells, the presented therapeutics consisting of glucose polymer and antisense peptide nucleic-acid-modified nanoparticles are selectively internalized into the human-derived multidrug-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus, and they display a much higher uptake rate (i.e., 51.6%). The developed strategy allows specific and efficient killing of nearly 100% of the antibiotic-resistant bacteria. Its significant curative efficacy against bacterial keratitis and endophthalmitis is also shown. This strategy will expand the focus of antisense technology to include bacterial cells other than mammalian cells.


Asunto(s)
Péptidos de Penetración Celular , Staphylococcus aureus Resistente a Meticilina , Animales , Humanos , Antibacterianos/química , Oligonucleótidos Antisentido/farmacología , Oligonucleótidos Antisentido/química , Azúcares , Bacterias , Escherichia coli , Adenosina Trifosfato , Mamíferos
14.
Chem Commun (Camb) ; 59(17): 2399-2412, 2023 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-36744435

RESUMEN

Biomedical imaging technology, which allows us to peer deeply within living subjects and visually explore the delivery and distribution of agents in living things, is producing tremendous opportunities for the early diagnosis and precise therapy of diseases. In this feature article, based on reviewing the latest representative examples of progress together with our recent efforts in the bioimaging field, we intend to introduce three typical kinds of non-invasive imaging technologies, i.e., fluorescence, ultrasonic and photoacoustic imaging, in which optical and/or acoustic signals are employed for analyzing various diseases. In particular, fluorescence imaging possesses a series of outstanding advantages, such as high temporal resolution, as well as rapid and sensitive feedback. Hence, in the first section, we will introduce the latest studies on developing novel fluorescence imaging methods for imaging bacterial infections, cancer and lymph node metastasis in a long-term and real-time manner. However, the issues of imaging penetration depth induced by photon scattering and light attenuation of biological tissue limit their widespread in vivo imaging applications. Taking advantage of the excellect penetration depth of acoustic signals, ultrasonic imaging has been widely applied for determining the location, size and shape of organs, identifying normal and abnormal tissues, as well as confirming the edges of lesions in hospitals. Thus, in the second section, we will briefly summarize recent advances in ultrasonic imaging techniques for diagnosing diseases in deep tissues. Nevertheless, the absence of lesion targeting and dependency on a professional technician may lead to the possibility of false-positive diagnosis. By combining the merits of both optical and acoustic signals, newly-developed photoacoustic imaging, simultaneously featuring higher temporal and spatial resolution with good sensitivity, as well as deeper penetration depth, is discussed in the third secretion. In the final part, we further discuss the major challenges and prospects for developing imaging technology for accurate disease diagnosis. We believe that these non-invasive imaging technologies will introduce a new perspective for the precise diagnosis of various diseases in the future.


Asunto(s)
Neoplasias , Técnicas Fotoacústicas , Humanos , Ultrasonido , Técnicas Fotoacústicas/métodos , Imagen Óptica , Acústica
15.
Anal Chem ; 95(4): 2303-2311, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36655772

RESUMEN

Sensitive and reliable clustered regularly interspaced short palindromic repeats (CRISPR) quantification without preamplification of the sample remains a challenge. Herein, we report a CRISPR Cas12a-powered silicon surface-enhanced Raman spectroscopy (SERS) ratiometric chip for sensitive and reliable quantification. As a proof-of-concept application, we select the platelet-derived growth factor-BB (PDGF-BB) as the target. We first develop a microfluidic synthetic strategy to prepare homogeneous silicon SERS substrates, in which uniform silver nanoparticles (AgNPs) are in situ grown on a silicon wafer (AgNPs@Si) by microfluidic galvanic deposition reactions. Next, one 5'-SH-3'-ROX-labeled single-stranded DNA (ssDNA) is modified on AgNPs via Ag-S bonds. In our design, such ssDNA has two fragments: one fragment hybridizes to its complementary DNA (5'-Cy3-labeled ssDNA) to form double-stranded DNA (dsDNA) and the other fragment labeled with 6'-carboxy-X-rhodmine (ROX) extends out as a substrate for Cas12a. The cleavage of the ROX-tagged fragment by Cas12a is controlled by the presence or not of PDGF-BB. Meanwhile, Cy3 molecules serving as internal standard molecules still stay at the end of the rigid dsDNA, and their signals remain constant. Thereby, the ratio of ROX signal intensity to Cy3 intensity can be employed for the reliable quantification of PDGF-BB concentration. The developed chip features an ultrahigh sensitivity (e.g., the limit of detection is as low as 3.2 pM, approximately 50 times more sensitive than the fluorescence counterpart) and good reproducibility (e.g., the relative standard deviation is less than 5%) in the detection of PDGF-BB.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Nanopartículas del Metal/química , Sistemas CRISPR-Cas/genética , Silicio/química , Espectrometría Raman/métodos , Becaplermina , Reproducibilidad de los Resultados , Plata/química , ADN/química , ADN de Cadena Simple
16.
J Am Chem Soc ; 144(51): 23522-23533, 2022 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-36508257

RESUMEN

Herein, we designed and synthesized a novel microRNA (miR)-responsive nanoantenna capable of early diagnosis and smart treatment of acute kidney injury (AKI). The nanoantenna was made of two miniature gold nanorods (AuNRs) (e.g., length: ∼48 nm; width: ∼9 nm) linked together by a rectangular DNA origami nanostructure (rDONs) scaffold (e.g., length: ∼90 nm; width: ∼60 nm) (rDONs@AuNR dimer). The surface plasmon resonance peak of the constructed nanoantenna is located within the NIR-II window (e.g., ∼1060 nm), thus guaranteeing photoacoustic (PA) imaging of the nanoantenna in deep tissues. Intriguingly, the nanoantenna displayed exclusive kidney retention in both healthy mice and ischemia reperfusion-induced AKI mice by leveraging the kidney-targeting ability of rDONs. Distinguished from the stable signals in the healthy mice, the PA signals of the nanoantenna would turn down in the AKI mice due to the AuNR detached from rDONs upon interaction with miR-21, which were up-expressed in AKI mice. The limit of detection toward miR-21 was down to 2.8 nM, enabling diagnosis of AKI as early as 10 min post-treatment with ischemia reperfusion, around 2 orders of magnitude earlier than most established probes. Moreover, the naked rDON scaffold generated by AKI could capture more reactive oxygen species (e.g., 1.5-fold more than rDONs@AuNR dimer), alleviating ischemic AKI. This strategy provided a new avenue for early diagnosis and smart treatment of AKI.


Asunto(s)
Lesión Renal Aguda , MicroARNs , Daño por Reperfusión , Ratones , Animales , Lesión Renal Aguda/diagnóstico por imagen , Lesión Renal Aguda/tratamiento farmacológico , Riñón , MicroARNs/genética , Isquemia , Diagnóstico Precoz , ADN
17.
Nat Commun ; 13(1): 5127, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36050316

RESUMEN

Bacteria can bypass the blood-brain barrier (BBB), suggesting the possibility of employment of bacteria for combating central nervous system diseases. Herein, we develop a bacteria-based drug delivery system for glioblastoma (GBM) photothermal immunotherapy. The system, which we name as 'Trojan bacteria', consists of bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles. In an orthotopic GBM mouse model, we demonstrate that the intravenously injected bacteria bypass the BBB, targeting and penetrating GBM tissues. Upon 808 nm-laser irradiation, the photothermal effects produced by ICG allow the destruction of bacterial cells and the adjacent tumour cells. Furthermore, the bacterial debris as well as the tumour-associated antigens promote antitumor immune responses that prolong the survival of GBM-bearing mice. Moreover, we demonstrate the residual bacteria are effectively eliminated from the body, supporting the potential therapeutic use of this system.


Asunto(s)
Glioblastoma , Nanopartículas , Animales , Bacterias , Línea Celular Tumoral , Glioblastoma/patología , Glucanos , Inmunoterapia , Ratones , Silicio
18.
Angew Chem Int Ed Engl ; 61(36): e202208422, 2022 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-35736400

RESUMEN

A novel bacteria-based drug delivery system, termed "Trojan nanobacteria system", has been developed in which nanoagents are internalized into engineered bacteria through bacteria-specific maltodextrin (MD) transporters. Compared to the method of attaching nanoagents to bacterial surfaces, this Trojan system features higher payloads and better stability. In cancer therapy, Trojan nanobacteria can specifically discriminate the tumor region and then penetrate deep tumor tissues. Once in the tumor, the Trojan nanobacteria systems are able to destroy deep tumor tissues due to the combined effects of antitumor protein expression (e.g., tumor necrosis factor-α, TNF-α) and photothermal properties.


Asunto(s)
Nanopartículas Calcificantes , Neoplasias , Bacterias , Humanos , Neoplasias/terapia
19.
Nat Commun ; 13(1): 1255, 2022 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-35273187

RESUMEN

Currently optical-based techniques for in vivo microbial population imaging are limited by low imaging depth and highly light-scattering tissue; and moreover, are generally effective against only one specific group of bacteria. Here, we introduce an imaging and therapy strategy, in which different bacteria actively eat the glucose polymer (GP)-modified gold nanoparticles through ATP-binding cassette (ABC) transporter pathway, followed by laser irradiation-mediated aggregation in the bacterial cells. As a result, the aggregates display ~15.2-fold enhancement in photoacoustic signals and ~3.0-fold enhancement in antibacterial rate compared with non-aggregated counterparts. Significantly, the developed strategy allows ultrasensitive imaging of bacteria in vivo as low ~105 colony-forming unit (CFU), which is around two orders of magnitude lower than most optical contrast agents. We further demonstrate the developed strategy enables the detection of ~107 CFU bacteria residing within tumour or gut. This technique enables visualization and treatment of diverse bacteria, setting the crucial step forward the study of microbial ecosystem.


Asunto(s)
Oro , Nanopartículas del Metal , Antibacterianos/química , Antibacterianos/farmacología , Bacterias , Ecosistema , Oro/química , Nanopartículas del Metal/química
20.
Anal Chem ; 94(14): 5699-5706, 2022 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-35344343

RESUMEN

Metal-organic frameworks (MOFs) are promising as novel disinfectants due to the reactive oxygen species (ROS) produced in their photocatalytic processes. The optimal MOF is screened as the best disinfectant, representing high-efficacy production of ROS under photocatalytic conditions. However, current methods to screen abundant MOFs for disinfectant application are generally semiquantitative or ex situ methods [such as electron paramagnetic resonance (EPR) measurements], so achieving a strategy that can quantitatively screen an optimal MOF in situ and is reliable is demanded. Herein, we developed a three-dimensional (3D) shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) platform to study the dynamic photocatalytic processes of various MOFs (e.g., ZIF-67, ZIF-8, and UIO-66) in situ. This platform comprises silica shell-isolated gold nanoparticles (AuNPs) modified on silicon nanowire arrays (SiNWArs). The MOF is then self-assembled on the 3D-SHINERS substrate. Using this platform, we recorded dynamic spectroscopic evidence of ROS formation by various MOFs under sunlight irradiation. By dynamic comparison, ZIF-67 has the most robust photocatalytic efficiency, ∼1.7-fold stronger than that of ZIF-8 and ∼42.6-fold stronger than that of UIO-66. As expected, ZIF-67 displays the best antibacterial ability, up to 99% in the agar plate assay. This work provides a versatile platform for dynamically monitoring photocatalytic performance and screening antibacterial MOFs.


Asunto(s)
Desinfectantes , Nanopartículas del Metal , Estructuras Metalorgánicas , Antibacterianos/farmacología , Oro/química , Nanopartículas del Metal/química , Estructuras Metalorgánicas/química , Ácidos Ftálicos , Especies Reactivas de Oxígeno , Espectrometría Raman
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