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1.
Colloids Surf B Biointerfaces ; 238: 113907, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38608464

RESUMO

Multifunctional agents with therapeutic and diagnostic capabilities are imperative to the prevention of Alzheimer's disease (AD), which is considered due to abnormal aggregation and deposition of ß-amyloid protein (Aß) as well as oxidative stress. Herein, quercetin (Que)- and p-phenylenediamine (p-PD)-derived red emission carbon dots (CDs) synthesized via a one-step hydrothermal method were designed as a novel theranostic nano-agent for the multi-target treatment of AD. R-CD-75 with an optimized composition exhibited significant inhibition of Aß aggregation and rapid depolymerization of mature Aß fibrils (<4 h) at micromolar concentrations (2 and 5 µg/mL, respectively). Moreover, R-CD-75 potently scavenged reactive oxygen species and showed turned-on red fluorescence imaging of Aß plaques both in vitro and in vivo. In vitro assays proved that R-CD-75 significantly mitigated the Aß-induced cytotoxicity and enhanced the cultured cell viability from 74.9 % to 98.0 %, while in vivo studies demonstrated that R-CD-75 prolonged the lifespan of AD nematodes by over 50 % (from 13 to 20 d). Compared to the precursors Que and p-PD, R-CD-75 inherited some of their structures and functional groups, such as aromatic structures, phenolic hydroxyl and amino groups, which were considered to interact with Aß species through hydrogen bonding, electrostatic interactions, hydrophobic interactions, and π-π stacking, thus contributing to its effectiveness in its theranostic functions. This research has opened a new avenue to the development of potent theranostic agents by designing novel carbon dots.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Carbono , Pontos Quânticos , Quercetina , Nanomedicina Teranóstica , Quercetina/química , Quercetina/farmacologia , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/química , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Carbono/química , Carbono/farmacologia , Pontos Quânticos/química , Animais , Humanos , Sobrevivência Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Tamanho da Partícula
2.
ACS Appl Mater Interfaces ; 16(15): 18534-18550, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38574189

RESUMO

The metastasis and recurrence of cancer are related to immunosuppression and hypoxia in the tumor microenvironment. Activating immune activity and improving the hypoxic environment face essential challenges. This paper reports on a multifunctional nanomaterial, HSCCMBC, that induces immunogenic cell death through powerful photodynamic therapy/chemodynamic therapy synergistic antitumor effects. The tumor microenvironment changed from the immunosuppressive type to immune type, activated the immune activity of the system, decomposed hydrogen peroxide to generate oxygen based on Fenton-like reaction, and effectively increased the level of intracellular O2 with the assistance of 3-bromopyruvate, a cell respiratory inhibitor. The structure and composition of HSCCMBC were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, infrared spectroscopy, etc. Oxygen probe RDPP was used to investigate the oxygen level inside and outside the cell, and hydroxyl radical probe tetramethylbenzidine was used to investigate the Fenton-like reaction ability. The immunofluorescence method investigated the expression of various immune markers and hypoxia-inducing factors in vitro and in vivo after treatment. In vitro and in vivo experiments indicate that HSCCMBC is an excellent antitumor agent and is expected to be a candidate drug for antitumor immunotherapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Dióxido de Silício/farmacologia , Cobre/química , Carbono/farmacologia , Morte Celular Imunogênica , Neoplasias/tratamento farmacológico , Oxigênio/química , Hipóxia , Linhagem Celular Tumoral , Peróxido de Hidrogênio/química , Microambiente Tumoral , Nanopartículas/química
3.
J Nanobiotechnology ; 22(1): 210, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671474

RESUMO

Carbon dots (CDs) are novel carbon-based nanomaterials that have been used as photosensitizer-mediated photodynamic therapy (PDT) in recent years due to their good photosensitizing activity. Photosensitizers (PSs) are main components of PDT that can produce large amounts of reactive oxygen species (ROS) when stimulated by light source, which have the advantages of low drug resistance and high therapeutic efficiency. CDs can generate ROS efficiently under irradiation and therefore have been extensively studied in disease local phototherapy. In tumor therapy, CDs can be used as PSs or PS carriers to participate in PDT and play an extremely important role. In bacterial infectious diseases, CDs exhibit high bactericidal activity as CDs are effective in disrupting bacterial cell membranes leading to bacterial death upon photoactivation. We focus on recent advances in the therapy of cancer and bacteria with CDs, and also briefly summarize the mechanisms and requirements for PSs in PDT of cancer, bacteria and other diseases. We also discuss the role CDs play in combination therapy and the potential for future applications against other pathogens.


Assuntos
Infecções Bacterianas , Carbono , Neoplasias , Fotoquimioterapia , Fármacos Fotossensibilizantes , Pontos Quânticos , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Humanos , Neoplasias/tratamento farmacológico , Carbono/química , Carbono/uso terapêutico , Carbono/farmacologia , Infecções Bacterianas/tratamento farmacológico , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Animais , Espécies Reativas de Oxigênio/metabolismo
4.
J Colloid Interface Sci ; 663: 577-590, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38428115

RESUMO

Photodynamic therapy (PDT) is limited in tumor therapy due to the mature antioxidant barrier of tumor microenvironment (TME) and phototoxicity/easy-degradation characteristics of photosensitizers. Therefore, we prepared Cu2+-doped hollow carbon nanoparticles (CHC) to protect the loaded photosensitizers and sensitize TME by glutathione-depletion and peroxidase (POD)-like activity for enhanced PDT. CHC significantly increased the maximum speed of POD-like reaction (Vm) of 8.4 times. By coating with hyaluronic acid (HA), the active sites on CHC were temporarily masked with low catalytic property, and restored in response to the overexpressed hyaluronidase in TME. Meanwhile, due to the excellent photothermal conversion efficiency (32.5 %) and hollow structure of CHC, the loaded photosensitizers were well protected from sunlight activation-induced unwanted phototoxicity and rapid degradation under the near-infrared light irradiation. In-vivo anti-tumor experiments demonstrated that the combination of photothermal-photodynamic effect achieved the best anti-tumor effect (tumor inhibition rate at 87.8 %) compared with any monotherapy. In addition, the combination of photothermal and photodynamic effect could efficiently suppress the cell migration, manifesting the reduced number of lung metastasized nodules by 74 %. This work provides an integrated platform for photosensitizers protection and TME sensitization for enhanced PDT.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/química , Carbono/farmacologia , Microambiente Tumoral , Neoplasias/tratamento farmacológico , Catálise , Linhagem Celular Tumoral , Nanopartículas/química , Peróxido de Hidrogênio
5.
J Colloid Interface Sci ; 663: 856-868, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38447400

RESUMO

Mitochondrial dysfunction and metal ion imbalance are recognized as pathological hallmarks of Alzheimer's Disease (AD), leading to deposition of ß-amyloid (Aß) thereby and inducing neurotoxicity, activating apoptosis, eliciting oxidative stress, and ultimately leading to cognitive impairment. In this study, the red blood cell membrane (RBC) was used as a vehicle for encapsulating carbon quantum dots (CQD) and polydopamine (PDA), creating a nanocomposite (PDA-CQD/RBC). This nanocomposite was combined with near-infrared light (NIR) for AD treatment. The RBC offers anti-immunorecognition properties to evade immune clearance, PDA exhibits enzyme-mimicking activity to mitigate oxidative stress damage, and CQD acts as a chelating agent for metal ions (Cu2+), effectively preventing Cu2+-mediated aggregation of Aß. Furthermore, the local heating induced by near-infrared laser irradiation can dismantle the formed Aß fibers and enhance the blood-brain barrier's permeability. Both in vitro and animal experiments have shown that PDA-CQD/RBC, in combination with NIR, mitigates neuroinflammation, and ameliorates behavioral deficits in mice. This approach targets multiple pathological pathways, surpassing the limitations of single-target treatments and enhancing therapeutic efficacy while decelerating disease progression.


Assuntos
Doença de Alzheimer , Indóis , Polímeros , Pontos Quânticos , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/patologia , Peptídeos beta-Amiloides , Metais , Raios Infravermelhos , Carbono/farmacologia
6.
J Colloid Interface Sci ; 665: 681-692, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38552583

RESUMO

The efficacy of electron-hole separation in a single sonosensitizer and the complexities of the tumor microenvironment (TME) present significant challenges to the effectiveness of sonodynamic therapy (SDT). Designing efficient sonosensitizers to enhance electron-hole separation and alleviate TME resistance is crucial yet challenging. Herein, we introduce a novel Z-scheme heterojunctions (HJs) sonosensitizer using Fe-doped carbon dots (CDs) as auxiliary semiconductors to sensitize cubic Cu2O (Fe-CDs@Cu2O) for the first time. Fe-CDs@Cu2O demonstrated enhanced SDT effects due to improved electron-hole separation. Additionally, the introduction of Fe ions in CDs synergistically enhances Fenton-like reactions with Cu ions in Cu2O, resulting in enhanced chemodynamic therapy (CDT) effects. Moreover, Fe-CDs@Cu2O exhibited rapid glutathione (GSH) depletion, effectively mitigating TME resistance. With high rates of 1O2 and OH generated by Fe-CDs@Cu2O, coupled with strong GSH depletion, single drug injection and ultrasound (US) irradiation effectively eliminate tumors. This innovative heterojunction sonosensitizer offers a promising pathway for clinical anti-tumor treatment.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Carbono/farmacologia , Elétrons , Glutationa , Íons , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Peróxido de Hidrogênio
7.
ACS Appl Mater Interfaces ; 16(12): 15457-15478, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38483821

RESUMO

The surface modification of magnetite nanoparticles (Fe3O4 NPs) is a promising approach to obtaining biocompatible and multifunctional nanoplatforms with numerous applications in biomedicine, for example, to fight cancer. However, little is known about the effects of Fe3O4 NP-associated reductive stress against cancer cells, especially against chemotherapy-induced drug-resistant senescent cancer cells. In the present study, Fe3O4 NPs in situ coated by dextran (Fe3O4@Dex) and glucosamine-based amorphous carbon coating (Fe3O4@aC) with potent reductive activity were characterized and tested against drug-induced senescent breast cancer cells (Hs 578T, BT-20, MDA-MB-468, and MDA-MB-175-VII cells). Fe3O4@aC caused a decrease in reactive oxygen species (ROS) production and an increase in the levels of antioxidant proteins FOXO3a, SOD1, and GPX4 that was accompanied by elevated levels of cell cycle inhibitors (p21, p27, and p57), proinflammatory (NFκB, IL-6, and IL-8) and autophagic (BECN1, LC3B) markers, nucleolar stress, and subsequent apoptotic cell death in etoposide-stimulated senescent breast cancer cells. Fe3O4@aC also promoted reductive stress-mediated cytotoxicity in nonsenescent breast cancer cells. We postulate that Fe3O4 NPs, in addition to their well-established hyperthermia and oxidative stress-mediated anticancer effects, can also be considered, if modified using amorphous carbon coating with reductive activity, as stimulators of reductive stress and cytotoxic effects in both senescent and nonsenescent breast cancer cells with different gene mutation statuses.


Assuntos
Antineoplásicos , Neoplasias da Mama , Hipertermia Induzida , Nanopartículas de Magnetita , Nanopartículas , Humanos , Feminino , Linhagem Celular Tumoral , Carbono/farmacologia , Neoplasias da Mama/tratamento farmacológico , Compostos Férricos/farmacologia , Antineoplásicos/farmacologia , Autofagia , Nanopartículas Magnéticas de Óxido de Ferro
8.
ACS Appl Mater Interfaces ; 16(13): 16653-16668, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38520338

RESUMO

Cancer metastasis and recurrence are closely associated with immunosuppression and a hypoxic tumor microenvironment. Chemodynamic therapy (CDT) and photothermodynamic therapy (PTT) have been shown to induce immunogenic cell death (ICD), effectively inhibiting cancer metastasis and recurrence when combined with immune adjuvants. However, the limited efficacy of Fenton's reaction and suboptimal photothermal effect present significant challenges for successfully inducing ICD through CDT and PTT. This paper described the synthesis and immunoantitumor activity of the novel iron-copper-doped folic acid carbon dots (CFCFB). Copper-doped folic acid carbon dots (Cu-FACDs) were initially synthesized via a hydrothermal method, using folic acid and copper gluconate as precursors. Subsequently, the nanoparticles CFCFB were obtained through cross-linking and self-assembly of Cu-FACDs with ferrocene dicarboxylic acid (FeDA) and 3-bromopyruvic acid (3BP). The catalytic effect of carbon dots in CFCFB enhanced the activity of the Fenton reaction, thereby promoting CDT-induced ICD and increasing the intracellular oxygen concentration. Additionally, 3BP inhibited cellular respiration, further amplifying the oxygen concentration. The photothermal conversion efficiency of CFCFB reached 55.8%, which significantly enhanced its antitumor efficacy through photothermal therapy. Immunofluorescence assay revealed that treatment with CFCFB led to an increased expression of ICD markers, including calreticulin (CRT) and ATP, as well as extracellular release of HMGB-1, indicating the induction of ICD by CFCFB. Moreover, the observed downregulation of ARG1 expression indicates a transition in the tumor microenvironment from an immunosuppressive state to an antitumor state following treatment with CFCFB. The upregulation of IL-2 and CD8 expression facilitated the differentiation of effector T cells, resulting in an augmented population of CD8+ T cells, thereby indicating the activation of systemic immune response.


Assuntos
Nanopartículas , Neoplasias , Humanos , Cobre/farmacologia , Linfócitos T CD8-Positivos , Ferro/farmacologia , Carbono/farmacologia , Ácido Fólico/farmacologia , Neoplasias/tratamento farmacológico , Oxigênio/farmacologia , Linhagem Celular Tumoral , Microambiente Tumoral , Peróxido de Hidrogênio
9.
Int J Nanomedicine ; 19: 2265-2284, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476273

RESUMO

Introduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications. Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined. Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1ß and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-ß. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function. Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.


Assuntos
Quitosana , Glaucoma , Traumatismo por Reperfusão , Ratos , Animais , Camundongos , Humanos , Microglia/patologia , Quitosana/farmacologia , Sirolimo/farmacologia , Carbono/farmacologia , Lipopolissacarídeos/farmacologia , Glaucoma/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Autofagia , Citocinas/metabolismo , Água , Traumatismo por Reperfusão/tratamento farmacológico
10.
J Nanobiotechnology ; 22(1): 100, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38462597

RESUMO

BACKGROUND: Despite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), the lack of efficient ferroptosis inducers and the poor solubility of photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination therapy of cancers. RESULTS: Herein, an ferroptosis/PDT integrated nanoplatform for melanoma therapy is constructed based on chlorin e6-modified Fe ions-doped carbon dots (Fe-CDs@Ce6). As a novel type of iron-carbon hybrid nanoparticles, the as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis and inhibit the migration of mouse skin melanoma cells (B16), but have no toxicity to normal cells. The nano-conjugated structures facilitate not only the aqueous dispersibility of Ce6, but also the self-accumulation ability of Fe-CDs@Ce6 within melanoma area without requiring extra targets. Moreover, the therapeutic effects of Fe-CDs@Ce6 are synergistically enhanced due to the increased GSH depletion by PDT and the elevated singlet oxygen (1O2) production efficiency by Fe-CDs. When combined with laser irradiation, the tumor growth can be significantly suppressed by Fe-CDs@Ce6 through cyclic administration. The T2-weighted magnetic resonance imaging (MRI) capability of Fe-CDs@Ce6 also reveals their potentials for cancer diagnosis and navigation therapy. CONCLUSIONS: Our findings indicate the multifunctionality of Fe-CDs@Ce6 in effectively combining ferroptosis/PDT therapy, tumor targeting and MRI imaging, which enables Fe-CDs@Ce6 to become promising biocompatible nanoplatform for the treatment of melanoma.


Assuntos
Ferroptose , Melanoma , Nanopartículas , Fotoquimioterapia , Camundongos , Animais , Fotoquimioterapia/métodos , Melanoma/tratamento farmacológico , Carbono/farmacologia , Carbono/química , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Imageamento por Ressonância Magnética , Nanopartículas/química
11.
Int J Nanomedicine ; 19: 1985-2004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435754

RESUMO

Introduction: The anti-cancer potency of copper-doped carbon quantum dots (Cu-CDs) against breast cancer progression needs more detailed investigations. Methods: With urea and ethylene glycol applied as carbon sources and copper sulfate used as a reactive dopant, Cu-CDs were synthesized in the current study by a one-step hydrothermal synthesis method, followed by the characterization and biocompatibility evaluations of Cu-CDs. Subsequently, the anti-cancer potency of Cu-CDs against breast cancer progression was confirmed by these biochemical, molecular, and transcriptomic assessments, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, and transcriptomic assays of MDA-MB-231 cells. Results: The biocompatibility of Cu-CDs was confirmed based on the non-significant changes in the pathological and physiological parameters in the Cu-CDs treated mice, as well as the noncytotoxic effect of Cu-CDs on normal cells. Moreover, the Cu-CDs treatments not only decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells but also induced the redox imbalance, cell cycle arrest, and apoptosis of MDA-MB-231 cells via ameliorating the mitochondrial dysfunctions and regulating the MAPK signaling pathway. Conclusion: Our findings confirmed the biosafety and excellent anti-cancer potency of Cu-CDs against breast cancer progression by tapping into mechanisms that disrupt malignant behaviors and oxidative homeostasis of breast cancer cells.


Assuntos
Neoplasias , Pontos Quânticos , Animais , Camundongos , Cobre/farmacologia , Apoptose , Carbono/farmacologia
12.
Colloids Surf B Biointerfaces ; 237: 113862, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518556

RESUMO

Clozapine, which is widely used to treat schizophrenia, shows low bioavailability due to poor solubility and high first-pass metabolism. The study aimed to design clozapine-loaded carbon dots (CDs) to enhance availability of the clozapine to the brain via intranasal pathway. The CDs were synthesized by pyrolysis of citric acid and urea at 200 °C by hydrothermal technique and characterized by photoluminescence, transmission electron microscopy (TEM), X-ray Photoelectron Spectrometer (XPS), and Fourier transform infrared spectrum (FTIR). The optimized clozapine-loaded CDs (CLZ-CDs-1:3-200) showed a quasi-spherical shape (9-12 nm) with stable blue fluorescence. The CDs showed high drug solubilization capacity (1.5 mg drug in 1 mg/ml CDs) with strong electrostatic interaction with clozapine (drug loading efficiency = 94.74%). The ex vivo release study performed using nasal goat mucosa showed sustained release of clozapine (43.89%) from CLZ-CDs-1:3-200 for 30 h. The ciliotoxicity study (histopathology) confirmed no toxicity to the nasal mucosal tissues using CDs. In the rat model (in vivo pharmacokinetic study), when CDs were administrated by the intranasal route, a significantly higher concentration of clozapine in the brain tissue (Cmax = 58.07 ± 5.36 µg/g and AUCt (µg/h*g) = 105.76 ± 12.31) was noted within a short time (tmax = 1 h) compared to clozapine suspension administered by intravenous route (Cmax = 20.99 ± 3.91 µg/g, AUC t (µg/h*g) = 56.89 ± 12.31, and tmax = 4 h). The high value of drug targeting efficiency (DTE, 486%) index and direct transport percentage (DTP, 58%) indicates the direct entry of clozapine-CDs in the brain via the olfactory route. In conclusion, designed CDs demonstrated a promising dosage form for targeted nose-to-brain delivery of clozapine for the effective treatment of schizophrenia.


Assuntos
Clozapina , Pontos Quânticos , Ratos , Animais , Carbono/farmacologia , Administração Intranasal , Encéfalo/metabolismo , Mucosa Nasal/metabolismo
13.
Biomaterials ; 308: 122547, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38537344

RESUMO

Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC), often reoccur due to the formation of intracellular bacterial colonies (IBCs) and antibiotic resistance. Given the significance of YadC for UPEC infection in our previous study, we developed D-xylose-decorated ɛ-poly-L-lysine (εPL)-based carbon dots (D-xyl@εPLCDs) that can be traced, and employed multi-step approaches to elucidate the functional roles of D-xyl@εPLCDs in UPEC infection. Compared to undecorated particles, D-xyl@εPLCDs demonstrate YadC-dependent bacterial targeting and exhibit enhanced bactericidal activities both intracellularly and extracellularly. Moreover, pre-treatment of D-xyl@εPLCDs before infection blocked the subsequent adhesion and invasion of UPEC to bladder epithelial cells 5637. Increase of ROS production and innate immune responses were observed in bladder epithelial cells 5637 treated with D-xyl@εPLCDs. In addition, treatment of D-xyl@εPLCDs post-infection facilitated clearance of UPEC in the bladders of the UTI mouse model, and reduced ultimate number of neutrophils, macrophages and inflammatory responses raised by invaded bacteria. Collectively, we presented a comprehensive evaluating system to show that D-xyl@εPLCDs exhibits superior bactericidal effects against UPEC, making them a promising candidate for drug development in clinical UTI therapeutics.


Assuntos
Carbono , Infecções Urinárias , Escherichia coli Uropatogênica , Xilose , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Animais , Carbono/química , Carbono/farmacologia , Escherichia coli Uropatogênica/efeitos dos fármacos , Humanos , Camundongos , Feminino , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Infecções por Escherichia coli/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Linhagem Celular , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico
14.
ACS Appl Bio Mater ; 7(3): 1958-1967, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38363649

RESUMO

Cancer remains a highly lethal disease due to its elusive early detection, rapid spread, and significant side effects. Nanomedicine has emerged as a promising platform for drug delivery, diagnosis, and treatment monitoring. In particular, carbon dots (CDs), a type of fluorescent nanomaterial, offer excellent fluorescence properties and the ability to carry multiple drugs simultaneously through covalent bonding. In this work, CDs with carbonyl groups on the surface were prepared by aldol condensation and reacted with amine groups in the structure of doxorubicin (DOX) through Schiff base reaction to generate pH-responsive CDs-DOX. On the other hand, cubosomes with three-dimensional lattice structures formed by lipid bilayers have advantageous capabilities of encapsulating various hydrophilic, amphiphilic, and hydrophobic substances. The pH-responsive CDs-DOX are subsequently loaded into cubosomes to form an anticancer therapeutic nanosystem, CDs-DOX@cubosome. Leveraging the unique properties of CDs-DOX and cubosomes, our CDs-DOX@cubosome can enter tumor tissue through the enhanced permeation and retention effect first and conduct membrane fusion with tumor cells to intracellularly release CDs-DOX. Then, the imine bond in CDs-DOX breaks under acidic conditions within human cancer cell lines (HeLa and HepG-2 cells), releasing DOX and achieving enhanced treatment of tumors. Additionally, fluorescent CDs can synchronously achieve real-time in situ diagnosis of tumor tissue. We demonstrate that our CDs-DOX@cubosome works as an excellent drug delivery system with therapeutic efficiency enhancement to the tumor and reduced side effects.


Assuntos
Carbono , Doxorrubicina , Humanos , Carbono/farmacologia , Carbono/química , Doxorrubicina/farmacologia , Doxorrubicina/química , Sistemas de Liberação de Medicamentos/métodos , Células HeLa , Concentração de Íons de Hidrogênio
15.
Artif Cells Nanomed Biotechnol ; 52(1): 131-144, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38423087

RESUMO

Most fungal bone and joint infections (arthritis) are caused by Mucormycosis (Mucor indicus). These infections may be difficult to treat and may lead to chronic bone disorders and disabilities, thus the use of new antifungal materials in bone disorders is vital, particularly in immunocompromised individuals, such as those who have contracted coronavirus disease 2019 (COVID-19). Herein, we reported for the first time the preparation of nitrogen-doped carbon quantum dots (N/CQDs) and a nitrogen-doped mesoporous carbon (N/MC) using a quick micro-wave preparation and hydrothermal approach. The structure and morphology were analysed using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and surface area analyser. Minimum inhibitory concentration (MIC), disc diffusion tests, minimum fungicidal concentration (MFC) and antifungal inhibitory percentages were measured to investigate the antifungal activity of N/CQDs and N/MC nanostructures. In addition to the in vivo antifungal activity in rats as determined by wound induction and infection, pathogen count and histological studies were also performed. According to in vitro and in vivo testing, both N/CQDs with small size and N/MC with porous structure had a significant antifungal impact on a variety of bone-infecting bacteria, including Mucor infection. In conclusion, the present investigation demonstrates that functional N/CQDs and N/MC are effective antifungal agents against a range of microbial pathogenic bone disorders in immunocompromised individuals, with stronger and superior fungicidal activity for N/CQDs than N/MC in vitro and in vivo studies.


Assuntos
Mucormicose , Pontos Quânticos , Ratos , Animais , Pontos Quânticos/química , Antifúngicos/farmacologia , Carbono/farmacologia , Carbono/química , Nitrogênio/química
16.
Arch Oral Biol ; 160: 105911, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38335699

RESUMO

OBJECTIVES: To study the effects of carbon dots (CDs), in combination with phytosphingosine (PHS), against acid-induced demineralization of hydroxyapatite in vitro. METHODS: CDs were generated from citric acid and urea by microwave heating. Transmission electron microscope (TEM), FT-IR, and fluorescence intensity were used to characterize the CDs. A hydroxyapatite (HAp) model was used to investigate the protective effects of CDs, PHS, and their combinations with and without a salivary pellicle against acid-induced demineralization in vitro. Ca2+ release as a parameter to evaluate the inhibition of demineralization was measured by capillary electrophoresis. The interactions between CDs, PHS, and HAp discs were investigated using a fluorescence detector. RESULTS: Uniform-sized CDs were synthesized, showing typical optical characteristics. CDs exhibited no inhibition of acid-induced demineralization in vitro, in contrast to PHS. Notably, a pre-coating of CDs increased the protective effects of PHS against acid-induced demineralization, which was not disturbed by the presence of a salivary pellicle and Tween 20. Scanning electron microscope (SEM) confirmed the binding and layers formed of both CDs and PHS to the HAp surfaces. Based on fluorescence spectra CDs binding to HAp seemed to be dependent on Ca2+ and PO43- interactions. CONCLUSIONS: CDs combined with PHS showed protective effects against acid-induced demineralization of HAp discs in vitro.


Assuntos
Durapatita , Esfingosina/análogos & derivados , Desmineralização do Dente , Humanos , Durapatita/farmacologia , Carbono/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
17.
J Colloid Interface Sci ; 663: 1-8, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38387182

RESUMO

We developed a new method to synthesize polyethylene glycol modified ultra small iron embedded in mesoporous carbon nanoparticle (C/Fe-PEG NP) for hydrogen (H2) assisted photothermal synergistic therapy. Herein, we use a simple in-situ reduction method to obtain the C/Fe NP in one-step carbonizing process, which is further modified by the biocompatible polyethylene glycol (PEG) on the surface of C/Fe NP to acquire high stability in physiological solutions. Utilizing the excellent photothermal property from the mesoporous carbon and the controllable H2 release property in the weakly acidic tumor microenvironment by the ultra-small Fe, the obtained C/Fe-PEG NPs can effective kill the cancer cells, meanwhile, protect normal cells without drugs. This selective anti-cancer mechanism of C/Fe-PEG NPs may because the produced H2 selective change the mitochondrial energy metabolism. In vivo results prove that the C/Fe-PEG NPs achieve excellent tumor ablation therapeutic effect and normal tissue protecting ability benefit from the H2-assisted photothermal therapy, promising the use of novel nanomaterials with more safety method for future cancer therapy.


Assuntos
Nanopartículas , Terapia Fototérmica , Ferro/farmacologia , Fototerapia , Polietilenoglicóis , Carbono/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico
18.
Int J Mol Sci ; 25(4)2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38396872

RESUMO

Carbon-semiconductor hybrid quantum dots are classical carbon dots with core carbon nanoparticles doped with a selected nanoscale semiconductor. Specifically, on those with the nanoscale TiO2 doping, denoted as CTiO2-Dots, their synthesis and thorough characterization were reported previously. In this work, the CTiO2-Dots were evaluated for their visible light-activated antibacterial function, with the results showing the effective killing of not only Gram-positive but also the generally more resistant Gram-negative bacteria. The hybrid dots are clearly more potent antibacterial agents than their neat carbon dot counterparts. Mechanistically, the higher antibacterial performance of the CTiO2-Dots is attributed to their superior photoexcited state properties, which are reflected by the observed much brighter fluorescence emissions. Also considered and discussed is the possibility of additional contributions to the antibacterial activities due to the photosensitization of the nanoscale TiO2 by its doped core carbon nanoparticles.


Assuntos
Pontos Quânticos , Carbono/farmacologia , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas
19.
Environ Sci Pollut Res Int ; 31(8): 12071-12082, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38227261

RESUMO

Microplastics (MPs) are widely distributed in soil environments, but their ecological risks are not fully understood. To fill this knowledge gap, incubation experiments were conducted to explore the physiological response of Eisenia foetida (E. fetida) to polyethylene MP stress and its effects on soil physicochemical properties. E. fetida was incubated in soils amended with MPs of two particle sizes (13 µm and 130 µm) at six concentrations (0, 1, 3, 6, 10 and 20 g MPs·kg-1 soil) under laboratory conditions. The toxicity of 13 µm MPs on the growth and survival of E. fetida was greater than that of 130 µm MPs. Excessive reactive oxygen species accumulation induced by high MP concentrations decreased superoxide dismutase activity and increased malondialdehyde content. Soil pH increased significantly in the 130 µm treatments. MPs increased the contents of soil organic carbon and available potassium. However, the presence of MPs did not significantly alter available phosphorus or nitrate nitrogen content. MP contamination in soil may have adverse impacts on the growth of earthworms, induce oxidative stress in earthworms, and change soil physicochemical properties. In addition, the effects of MPs are size-dependent and dose-dependent. This study provides new evidence for the ecological risks of MP pollution in the earthworm-soil systems.


Assuntos
Oligoquetos , Poluentes do Solo , Animais , Microplásticos/toxicidade , Polietileno/toxicidade , Plásticos/toxicidade , Solo/química , Carbono/farmacologia , Poluentes do Solo/análise
20.
Sci Rep ; 14(1): 1100, 2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212628

RESUMO

The growing popularity of nano-fertilization around the world for enhancing yield and nutrient use efficiency has been realized, however its influence on soil microbial structure is not fully understood. The purpose of carrying out this study was to assess the combined effect of nano and conventional fertilizers on the soil biological indicators and crop yield in a wheat-maize system. The results indicate that the at par grain yield of wheat and maize was obtained with application of 75% of recommended nitrogen (N) with full dose of phosphorus (P) and potassium (K) through conventional fertilizers along with nano-N (nano-urea) or nano-N plus nano-Zn sprays and N100PK i.e. business as usual (recommended dose of fertilizer). Important soil microbial property like microbial biomass carbon was found statistically similar with nano fertilizer-based management (N75PK + nano-N, and N75PK + nano-N + nano-Zn) and conventional management (N100PK), during both wheat and maize seasons. The experimental data indicated that the application of foliar spray of nano-fertilizers along with 75% N as basal is a sustainable nutrient management approach with respect to growth, yield and rhizosphere biological activity. Furthermore, two foliar sprays of nano-N or nano-N + nano-Zn curtailed N requirement by 25%, furthermore enhanced soil microbial diversity and the microbial community structure. The specific microbial groups, including Actinobacteria, Bacteroidia, and Proteobacteria, were present in abundance and were positively correlated with wheat and maize yield and soil microbial biomass carbon. Thus, one of the best nutrient management approaches for sustaining productivity and maintaining sound microbial diversity in wheat-maize rotation is the combined use of nano-fertilizers and conventional fertilizers.


Assuntos
Agricultura , Microbiota , Agricultura/métodos , Fertilizantes , Triticum , Zea mays , Nitrogênio/análise , Zinco/farmacologia , Solo/química , Carbono/farmacologia
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