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1.
Biosensors (Basel) ; 14(7)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39056602

RESUMO

Mesoporous silica nanoparticles (MSNs) exhibit highly beneficial characteristics for devising efficient biosensors for different analytes. Their unique properties, such as capabilities for stable covalent binding to recognition groups (e.g., antibodies or aptamers) and sensing surfaces, open a plethora of opportunities for biosensor construction. In addition, their structured porosity offers capabilities for entrapping signaling molecules (dyes or electroactive species), which could be released efficiently in response to a desired analyte for effective optical or electrochemical detection. This work offers an overview of recent research studies (in the last five years) that contain MSNs in their optical and electrochemical sensing platforms for the detection of cancer biomarkers, classified by cancer type. In addition, this study provides an overview of cancer biomarkers, as well as electrochemical and optical detection methods in general.


Assuntos
Biomarcadores Tumorais , Técnicas Biossensoriais , Nanopartículas , Dióxido de Silício , Dióxido de Silício/química , Biomarcadores Tumorais/análise , Nanopartículas/química , Humanos , Porosidade , Neoplasias/diagnóstico , Técnicas Eletroquímicas
2.
ACS Appl Mater Interfaces ; 16(26): 33081-33092, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38888094

RESUMO

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that affects the gastrointestinal tract. The major hurdles impeding IBD treatment are the low targeting efficiency and short retention time of drugs in IBD sites. Nanoparticles with specific shapes have demonstrated the ability to improve mucus retention and cellular uptake. Herein, mesoporous silica nanoparticles (MSNs) with various morphologies were used to deliver budesonide (BUD) for the treatment of IBD. The therapeutic efficacy is strongly dependent on their shapes. The system comprises different shapes of MSNs as carriers for budesonide (BUD), along with Eudragit S100 as the enteric release shell. The encapsulation of Eudragit S100 not only improved the stability of MSNs-BUD in the gastrointestinal tract but also conferred pH-responsive drug release properties. Then, MSNs efficiently deliver BUD to the colon site, and the special shape of MSNs plays a critical role in enhancing their permeability and retention in the mucus layer. Among them, dendritic MSNs (MSND) effectively reduced myeloperoxidase (MPO) activity and levels of inflammatory cytokines in the colon due to long retention time and rapid release in IBD sites, thereby enhancing the therapeutic efficacy against colitis. Given the special shapes of MSNs and pH-responsivity of Eudragit S100, BUD loaded in the voids of MSND (E@MSNs-BUD) could penetrate the mucous layer and be accurately delivered to the colon with minor side effects. This system is expected to complement current treatment strategies for the IBD.


Assuntos
Budesonida , Portadores de Fármacos , Doenças Inflamatórias Intestinais , Nanopartículas , Dióxido de Silício , Budesonida/química , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Budesonida/farmacocinética , Nanopartículas/química , Nanopartículas/uso terapêutico , Animais , Dióxido de Silício/química , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Portadores de Fármacos/química , Camundongos , Ácidos Polimetacrílicos/química , Liberação Controlada de Fármacos , Humanos , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Porosidade , Concentração de Íons de Hidrogênio
3.
Mikrochim Acta ; 191(6): 326, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740583

RESUMO

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.


Assuntos
Movimento Celular , Quimioterapia Combinada , Nanopartículas , Neoplasias , Dióxido de Silício , Movimento Celular/efeitos dos fármacos , Dióxido de Silício/química , Quimioterapia Combinada/métodos , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas/química , Sistemas de Liberação de Fármacos por Nanopartículas/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanopartículas/ultraestrutura , Células A549 , Microscopia Eletrônica de Transmissão , Humanos
4.
Pharmaceutics ; 16(5)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38794294

RESUMO

A nanoparticle's shape is a critical determinant of its biological interactions and therapeutic effectiveness. This study investigates the influence of shape on the performance of mesoporous silica nanoparticles (MSNs) in anticancer therapy. MSNs with spherical, rod-like, and hexagonal-plate-like shapes were synthesized, with particle sizes of around 240 nm, and their other surface properties were characterized. The drug loading capacities of the three shapes were controlled to be 47.46%, 49.41%, and 46.65%, respectively. The effects of shape on the release behaviors, cellular uptake mechanisms, and pharmacological behaviors of MSNs were systematically investigated. Through a series of in vitro studies using 4T1 cells and in vivo evaluations in 4T1 tumor-bearing mice, the release kinetics, cellular behaviors, pharmacological effects, circulation profiles, and therapeutic efficacy of MSNs were comprehensively assessed. Notably, hexagonal-plate-shaped MSNs loaded with PTX exhibited a prolonged circulation time (t1/2 = 13.59 ± 0.96 h), which was approximately 1.3 times that of spherical MSNs (t1/2 = 10.16 ± 0.38 h) and 1.5 times that of rod-shaped MSNs (t1/2 = 8.76 ± 1.37 h). This research underscores the significance of nanoparticles' shapes in dictating their biological interactions and therapeutic outcomes, providing valuable insights for the rational design of targeted drug delivery systems in cancer therapy.

5.
Sci Rep ; 14(1): 12132, 2024 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802497

RESUMO

The striatum plays a crucial role in providing input to the basal ganglia circuit and is implicated in the pathological process of Parkinson's disease (PD). Disruption of the dynamic equilibrium in the basal ganglia loop can be attributed to the abnormal functioning of the medium spiny neurons (MSNs) within the striatum, potentially acting as a trigger for PD. Exercise has been shown to mitigate striatal neuronal dysfunction through neuroprotective and neurorestorative effects and to improve behavioral deficits in PD model mice. In addition, this effect is offset by the activation of MSNs expressing dopamine D2 receptors (D2-MSNs). In the current study, we investigated the underlying neurobiological mechanisms of this effect. Our findings indicated that exercise reduces the power spectral density of the beta-band in the striatum and decreases the overall firing frequency of MSNs, particularly in the case of striatal D2-MSNs. These observations were consistent with the results of molecular biology experiments, which revealed that aerobic training specifically enhanced the expression of striatal dopamine D2 receptors (D2R). Taken together, our results suggest that aerobic training aimed at upregulating striatal D2R expression to inhibit the functional activity of D2-MSNs represents a potential therapeutic strategy for the amelioration of motor dysfunction in PD.


Assuntos
Corpo Estriado , Modelos Animais de Doenças , Doença de Parkinson , Condicionamento Físico Animal , Receptores de Dopamina D2 , Animais , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/genética , Corpo Estriado/metabolismo , Camundongos , Doença de Parkinson/terapia , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Masculino , Neurônios/metabolismo , Camundongos Endogâmicos C57BL , Atividade Motora/fisiologia , Neurônios Espinhosos Médios
6.
Heliyon ; 10(8): e29460, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38665554

RESUMO

This research aimed to enhance dermal delivery and optimize depigmentation therapy by designing mesoporous silica nanoparticles (MSNs) encapsulating azelaic acid (AZA) within a gel matrix. The MSNs were prepared using the sol-gel method. After subsequent processes, including acid extraction and drug loading, were then elucidated through PDI, size, zeta-potential, entrapment efficiency, nitrogen adsorption assay, FE-SEM, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and tyrosinase inhibition assay, were employed to assess the formulation. In-vitro stability tests for both AZA-MSN gel (AZCG) and AZA-loaded mesoporous silica gel (AZMG) were conducted at 8 °C, 25 °C, 40 °C, and 40 °C + 75 % RH, encompassing assessments of color, liquefaction, pH, and conductivity. Our findings showed a notable entrapment efficiency of 93.46 % for AZA-MSNs, with FE-SEM illustrating porous spherical MSNs. The particle size of AZA-MSNs was determined to be 211.9 nm, with a pore size of 2.47 nm and XRD analysis confirmed the amorphous state of AZA within the MSN carriers. Rheology examination indicated a non-Newtonian flow, while ex-vivo rat skin permeation studies conducted in a phosphate buffer (pH = 5.5) demonstrated a biphasic release pattern with 85.53 % cumulative drug permeation for AZA-MSNs. Overall, the study endorse the potential of AZA-MSNs as an efficacious and stable formulation for AZA delivery, highlighting their promise in addressing pigmentation concerns compared to conventional approaches.

7.
Adv Healthc Mater ; 13(17): e2304150, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38554019

RESUMO

D-mannose is widely used as non-antibiotic treatment for bacterial urinary tract infections. This application is based on a well-studied mechanism of binding to the type 1 bacterial pili and, therefore, blocking bacteria adhesion to the uroepithelial cells. To implement D-mannose into carrier systems, the mechanism of action of the sugar in the bladder environment is also relevant and requires investigation. Herein, two different MANNosylation strategies using mesoporous silica nanoparticles (MSNs) are described. The impact of different chemical linkers on bacterial adhesion and bladder cell response is studied via confocal microscopy imaging of the MSN interactions with the respective organisms. Cytotoxicity is assessed and the expression of Toll-like receptor 4 (TLR4) and caveolin-1 (CAV-1), in the presence or absence of simulated infection with bacterial lipopolysaccharide (LPS), is evaluated using the human urinary bladder cancer cell line T24. Further, localisation of the transcription factor NF-κB due to the MANNosylated materials is examined over time. The results show that MANNosylation modifies bacterial adhesion to the nanomaterials and significantly affects TLR4, caveolin-1, and NF-κB in bladder cells. These elements are essential components of the inflammatory cascade/pathogens response during urinary tract infections. These findings demonstrate that MANNosylation is a versatile tool to design hybrid nanocarriers for targeted biomedical applications.


Assuntos
Manose , NF-kappa B , Nanopartículas , Dióxido de Silício , Receptor 4 Toll-Like , Neoplasias da Bexiga Urinária , Humanos , Receptor 4 Toll-Like/metabolismo , Dióxido de Silício/química , Nanopartículas/química , NF-kappa B/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Manose/química , Linhagem Celular Tumoral , Aderência Bacteriana/efeitos dos fármacos , Caveolina 1/metabolismo , Porosidade , Lipopolissacarídeos
8.
Int J Nanomedicine ; 19: 2675-2690, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505168

RESUMO

Purpose: 5-fluorouracil (5-FU) is a first-line chemotherapeutic agent used to treat colorectal cancer (CRC). However, 5-FU induces drug resistance and activation of cancer stem cells (CSCs). In the present study, we designed a novel biocompatible nanomedicine system with high efficacy and biocompatibility by synthesizing mesoporous silica nanoparticle (MSN)-structured ZnO and gold ions. Oleuropein (OLP) is a phenolic compound derived from olive leaves that exerts anti-cancer effects. Therefore, we synthesized OLP-loaded ZnO/Au MSNs (ZnO/Au/OLP MSNs) and examined their anti-cancer effects on 5-FU-resistant CRC cells. Methods: ZnO/Au MSNs were synthesized and functionalized, and their physical and chemical compositions were characterized using UV-visible spectroscopy, dynamic light scattering, and transmission electron microscopy (TEM). Their effects were assessed in terms of cellular proliferation capacity, migration and invasion ability, colony-forming ability, spheroid-forming ability, reactive oxygen species (ROS) production, and mitochondrial membrane depolarization. Results: ZnO/Au MSNs were mostly composed of various ions containing ZnO and gold ions, had a spheroid phenotype, and exhibited no cytotoxicity. ZnO/Au/OLP MSNs reduced cell viability and CSC formation and induced apoptosis of 5-FU-resistant CRC cells via necrosis via ROS accumulation and DNA fragmentation. Conclusion: ZnO/Au/OLP MSNs exhibited anti-cancer activity by upregulating necrosis. These results revealed that ZnO/Au/OLP MSNs are a novel drug delivery system for 5-FU CRC therapy.


Assuntos
Neoplasias Colorretais , Glucosídeos Iridoides , Nanopartículas , Óxido de Zinco , Humanos , Dióxido de Silício/química , Espécies Reativas de Oxigênio , Nanopartículas/química , Fluoruracila/farmacologia , Necrose , Ouro/química , Íons , Neoplasias Colorretais/tratamento farmacológico , Porosidade
9.
Lasers Med Sci ; 39(1): 45, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38253944

RESUMO

Chlorophyll (Chl) is a promising natural photosensitizer (PS) in photodynamic treatment (PDT). Mesoporous silica nanoparticles (MSNs) were chosen to increase the effectiveness of PDT. This study aimed to evaluate the synergistic efficacy of chlorophyll-loaded mesoporous silica nanoparticles (Chl-MSNs) with photodynamic therapy (PDT) and to investigate their potential toxicity in HepG2, MDA-MB-231, and HSF cell lines. Chl-MSNs were prepared via the physical adsorption method. TEM, DLS, and zeta potential examined morphology, size, and surface characteristics. MSNs and Chl-MSNs were characterized using the same techniques. HPLC was used to assess the encapsulation efficiency. At pH 7.4, an in vitro release experiment of Chl-MSNs was performed. Chl, MSNs, and Chl-MSNs were applied to the three cell lines at different concentrations and subjected to red (650 nm) and blue (450-500 nm) lasers. MSNs and Chl-MSNs' sizes were 90.338 ± 38.49 nm and 123.84 ± 15.67 nm, respectively, as obtained by TEM; the hydrodynamic diameter for MSNs (93.69 ± 20.53 nm) and Chl-MSNs (212.95 ± 19.76 nm); and their zeta potential values are - 16.7 ± 2.19 mV and - 18.84 ± 1.40 mV. The encapsulation efficiency of Chl-MSNs was 70%. Chl-MSNs displayed no toxicity in dark conditions but showed excellent photostability under blue and red light exposure. Furthermore, using Chl over Chl-MSNs has a higher PDT efficiency than the tested cell lines. Chl-MSNs have the potential to be an effective delivery system. PDT proved to be an essential technique for cancer treatment. Blue laser is recommended over red laser with Chl and MSNs for destroying cancer cells.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Linhagem Celular , Clorofila/farmacologia , Neoplasias/tratamento farmacológico , Dióxido de Silício
10.
Biomater Adv ; 154: 213647, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37839298

RESUMO

The development of suitable bioinks with high printability, mechanical strength, biodegradability, and biocompatibility is a key challenge for the clinical translation of 3D constructs produced with bioprinting technologies. In this work, we developed a new type of nanocomposite bioinks containing thiolated mesoporous silica nanoparticles (MSN) that act as active fillers within norbornene-functionalized hydrogels. The MSNs could rapidly covalently crosslink the hydrogels upon exposure to UV light. The mechanical properties of the gels could be modulated from 9.3 to 19.7 kPa with increasing concentrations of MSN. The ability of the MSN to covalently crosslink polymeric networks was, however, significantly influenced by polymer architecture and the number of functional groups. Modification of the outer surface of MSNs with matrix metalloproteinase (MMP) sensitive peptides (MSN-MMPs) resulted in proteinase K and MMP-9 enzyme responsive biodegradable bioinks. Additional cysteine modified RGD peptide incorporation enhanced cell-matrix interactions and reduced the gelation time for bioprinting. The nanocomposite bioinks could be printed by using extrusion-based bioprinting. Our nanocomposite bioinks preserved their shape during in vitro studies and encapsulated MG63 cells preserved their viability and proliferated within the bioinks. As such, our nanocomposite bioinks are promising bioinks for creating bioprinted constructs with tunable mechanical and degradation properties.


Assuntos
Bioimpressão , Nanocompostos , Alicerces Teciduais/química , Bioimpressão/métodos , Impressão Tridimensional , Hidrogéis
11.
Int J Pharm ; 645: 123373, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37673281

RESUMO

Psoriasis is an inflammatory skin disease accompanied with chronic papulosquamous lesions and multiple comorbidities that considerably affect patients' quality of life. In order to develop an enhanced therapeutic strategy for psoriasis, 5-demethylnobiletin (5-DN), a kind of polymethoxyflavones (PMFs) with high anti-inflammatory activity, was delivered in vitro and in vivo by the nanocarrier of mesoporous silica nanoparticles (MSNs) both in the human keratinocytes HaCaT cell line and the mouse model with psoriasis-like lesions. The drug-loaded nanocarrier system (MSNs@5-DN) significantly improved the biocompatibility and bioavailability of 5-DN. Investigations at cell biological, histopathological, and molecular levels revealed the pharmacological mechanism of the drug delivery system, including the inhibition of inflammatory responses by downregulating the proinflammatory cytokine levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6). The upregulation of anti­inflammatory cytokine of transforming growth factor-ß1 (TGF-ß1) and microRNA-17-5p, a critical regulator of the PTEN/AKT pathway, was also observed. The psoriasis-like lesions were markedly ameliorated in the mouse models treated with MSNs@5-DN. The designed drug-loading system shows an enhanced therapeutic outcome for psoriasis-like lesion compared with free 5-DN. This study revealed the synergistic effect of functionalized MSNs loaded with PMFs on the clinical treatment of human psoriasis.


Assuntos
MicroRNAs , Nanopartículas , Psoríase , Animais , Camundongos , Humanos , Espécies Reativas de Oxigênio , Dióxido de Silício/química , Qualidade de Vida , Nanopartículas/química , Psoríase/tratamento farmacológico , Citocinas , Anti-Inflamatórios/farmacologia , Concentração de Íons de Hidrogênio , Porosidade
12.
Neuropharmacology ; 240: 109714, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37690678

RESUMO

Physical inactivity is a global epidemic. People who take the initiative to exercise will feel pleasure during the exercise process and stick with it for a long time, while people who passively ask for exercise will feel pain and cannot stick with it. However, the neural mechanisms underlying voluntary and forced exercise remain unclear. Here, we report that voluntary running increased the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSC) but decreased membrane excitability in D1R-MSNs, whereas D2R-MSNs did not change in mEPSC and membrane excitability. Forced running increased the frequency of mEPSC and membrane excitability in D2R-MSNs, but D1R-MSNs did not change, which may be the mechanism by which forced exercise has a non-rewarding effect. These findings provide new insights into how voluntary and forced exercise mediate reward and non-reward effects.

13.
Adv Drug Deliv Rev ; 201: 115049, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37573951

RESUMO

Mesoporous silica nanoparticles (MSNs) have attracted the attention of chemists, who have developed numerous systems for the encapsulation of a plethora of molecules, allowing the use of mesoporous silica nanoparticles for biomedical applications. MSNs have been extensively studied for their use in nanomedicine, in applications such as drug delivery, diagnosis, and bioimaging, demonstrating significant in vivo efficacy in different preclinical models. Nevertheless, for the transition of MSNs into clinical trials, it is imperative to understand the characteristics that make MSNs effective and safe. The biosafety properties of MSNs in vivo are greatly influenced by their physicochemical characteristics such as particle shape, size, surface modification, and silica framework. In this review, we compile the most relevant and recent progress in the literature up to the present by analyzing the contributions on biodistribution, biodegradability, and clearance of MSNs. Furthermore, the ongoing clinical trials and the potential challenges related to the administration of silica materials for advanced therapeutics are discussed. This approach aims to provide a solid overview of the state-of-the-art in this field and to encourage the translation of MSNs to the clinic.


Assuntos
Nanopartículas , Dióxido de Silício , Humanos , Distribuição Tecidual , Contenção de Riscos Biológicos , Porosidade , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Portadores de Fármacos/química
14.
Anal Chim Acta ; 1274: 341541, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37455074

RESUMO

Development of new strategies in photoelectrochemical (PEC) sensors is an important way to realize sensitive detection of biomolecule. In this study, mesoporous silica nanospheres (MSNs)-assisted split-type PEC aptasensor with in situ generation of Bi2S3 was proposed to achieve reliable detection of prostate-specific antigen (PSA). To be more specific, this bioresponsive release system will release large amounts of Na2S by the reaction between PSA and aptamer that capped Na2S-loading MSNs. Next, the Na2S reacts with Bi to yield BiOI/BiOBr/Bi2S3 composite, which leads to an alteration in the electron-hole transfer pathway of the photoelectric material and a decrease in the response. As the PSA concentration increases, more Na2S can be released and lower photocurrent is obtained. The linear range under the optimal experimental conditions is 10 pg·mL-1-1 µg⋅mL-1, and the detection limit is 1.23 pg⋅mL-1, which has satisfactory stability and anti-interference.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Humanos , Masculino , Antígeno Prostático Específico , Técnicas Eletroquímicas , Aptâmeros de Nucleotídeos/química , Dióxido de Silício , Limite de Detecção
15.
J Psychiatr Res ; 163: 180-194, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37216772

RESUMO

BACKGROUND: Posttraumatic stress disorder (PTSD), a psychiatric disorder caused by stressful events, is characterized by long-lasting fear memory. The nucleus accumbens shell (NAcS) is a key brain region that regulates fear-associated behavior. Small-conductance calcium-activated potassium channels (SK channels) play a key role in regulating the excitability of NAcS medium spiny neurons (MSNs) but their mechanisms of action in fear freezing are unclear. METHOD: We established an animal model of traumatic memory using conditioned fear freezing paradigm, and investigated the alterations in SK channels of NAc MSNs subsequent to fear conditioning in mice. We then utilized an adeno-associated virus (AAV) transfection system to overexpress the SK3 subunit and explore the function of the NAcS MSNs SK3 channel in conditioned fear freezing. RESULTS: Fear conditioning activated NAcS MSNs with enhanced excitability and reduced the SK channel-mediated medium after-hyperpolarization (mAHP) amplitude. The expression of NAcS SK3 were also reduced time-dependently. The overexpression of NAcS SK3 impaired conditioned fear consolidation without affecting conditioned fear expression, and blocked fear conditioning-induced alterations in NAcS MSNs excitability and mAHP amplitude. Additionally, the amplitudes of mEPSC, AMPAR/NMDAR ratio, and membrane surface GluA1/A2 expression in NAcS MSNs was increased by fear conditioning and returned to normal levels upon SK3 overexpression, indicating that fear conditioning-induced decrease of SK3 expression caused postsynaptic excitation by facilitating AMPAR transmission to the membrane. CONCLUSION: These findings show that the NAcS MSNs SK3 channel plays a critical role in conditioned fear consolidation and that it may influence PTSD pathogenesis, making it a potential therapeutic target against PTSD.


Assuntos
Transtornos Fóbicos , Canais de Potássio Ativados por Cálcio de Condutância Baixa , Camundongos , Animais , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo , Núcleo Accumbens/metabolismo , Congelamento , Medo
16.
Mol Pharm ; 20(6): 3187-3201, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-37167021

RESUMO

Mesoporous silica nanoparticles (MSNs) are widely used in the biomedical field because of their unique and excellent properties. However, the potential toxicity of different shaped MSNs via injection has not been fully studied. This study aims to systematically explore the impact of shape and shear stress on the toxicity of MSNs after injection. An in vitro blood flow model was developed to investigate the cytotoxicity and the underlying mechanisms of spherical MSNs (S-MSN) and rodlike MSNs (R-MSN) in human umbilical vein endothelial cells (HUVECs). The results suggested that the interactions between MSNs and HUVECs under the physiological flow conditions were significantly different from that under static conditions. Whether under static or flow conditions, R-MSN showed better cellular uptake and less oxidative damage than S-MSN. The main mechanism of cytotoxicity induced by R-MSN was due to shear stress-dependent mechanical damage of the cell membrane, while the toxicity of S-MSN was attributed to mechanical damage and oxidative damage. The addition of fetal bovine serum (FBS) alleviated the toxicity of S-MSN by reducing cellular uptake and oxidative stress under static and flow conditions. Moreover, the in vivo results showed that both S-MSN and R-MSN caused cardiovascular toxicity in zebrafish and mouse models due to the high shear stress, especially in the heart. S-MSN led to severe oxidative damage at the accumulation site, such as liver, spleen, and lung in mice, while R-MSN did not cause significant oxidative stress. The results of in vitro blood flow and in vivo models indicated that particle shape and shear stress are crucial to the biosafety of MSNs, providing new evidence for the toxicity mechanisms of the injected MSNs.


Assuntos
Nanopartículas , Dióxido de Silício , Camundongos , Humanos , Animais , Porosidade , Dióxido de Silício/toxicidade , Células Endoteliais , Peixe-Zebra , Nanopartículas/toxicidade
17.
Neuron ; 111(10): 1626-1636.e6, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-36917979

RESUMO

Lasker's award-winning drug propofol is widely used in general anesthesia. The recreational use of propofol is reported to produce a well-rested feeling and euphoric state; yet, the neural mechanisms underlying such pleasant effects remain unelucidated. Here, we report that propofol actively and directly binds to the dopamine transporter (DAT), but not the serotonin transporter (SERT), which contributes to the rapid relief of anhedonia. Then, we predict the binding mode of propofol by molecular docking and mutation of critical binding residues on the DAT. Fiber photometry recording on awake freely moving mice and [18F] FP-CIT-PET scanning further establishes that propofol administration evokes rapid and lasting dopamine accumulation in nucleus accumbens (NAc). The enhanced dopaminergic tone drives biased activation of dopamine-receptor-1-expressing medium spiny neurons (D1-MSNs) in NAc and reverses anhedonia in chronically stressed animals. Collectively, these findings suggest the therapeutic potential of propofol against anhedonia, which warrants future clinical investigations.


Assuntos
Dopamina , Propofol , Camundongos , Animais , Dopamina/metabolismo , Propofol/farmacologia , Propofol/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Simulação de Acoplamento Molecular , Receptores de Dopamina D1/metabolismo , Núcleo Accumbens/fisiologia , Anedonia , Camundongos Endogâmicos C57BL
18.
Front Cell Infect Microbiol ; 13: 1124411, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36864881

RESUMO

Mesoporous silica nanoparticles (MSNs) hold promise as safer and more effective medication delivery vehicles for treating oral disorders. As the drug's delivery system, MSNs adapt to effectively combine with a variety of medications to get over systemic toxicity and low solubility issues. MSNs, which operate as a common nanoplatform for the co-delivery of several compounds, increase therapy effectiveness and show promise in the fight against antibiotic resistance. MSNs offer a noninvasive and biocompatible platform for delivery that produces long-acting release by responding to minute stimuli in the cellular environmen. MSN-based drug delivery systems for the treatment of periodontitis, cancer, dentin hypersensitivity, and dental cavities have recently been developed as a result of recent unparalleled advancements. The applications of MSNs to be embellished by oral therapeutic agents in stomatology are discussed in this paper.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas , Administração Oral , Dióxido de Silício , Solubilidade
19.
Front Pharmacol ; 14: 1117052, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36843953

RESUMO

Multifunctional nanocarrier platforms have shown great potential for the diagnosis and treatment of liver cancer. Here, a novel nucleolin-responsive nanoparticle platform was constructed for the concurrent detection of nucleolin and treatment of liver cancer. The incorporation of AS1411 aptamer, icaritin (ICT) and FITC into mesoporous silica nanoparticles, labelled as Atp-MSN (ICT@FITC) NPs, was the key to offer functionalities. The specific combination of the target nucleolin and AS1411 aptamer caused AS1411 to separate from mesoporous silica nanoparticles surface, allowing FITC and ICT to be released. Subsequently, nucleolin could be detected by monitoring the fluorescence intensity. In addition, Atp-MSN (ICT@FITC) NPs can not only inhibit cell proliferation but also improve the level of ROS while activating the Bax/Bcl-2/caspase-3 signalling pathway to induce apoptosis in vitro and in vivo. Moreover, our results demonstrated that Atp-MSN (ICT@FITC) NPs had low toxicity and could induce CD3+ T-cell infiltration. As a result, Atp-MSN (ICT@FITC) NPs may provide a reliable and secure platform for the simultaneous identification and treatment of liver cancer.

20.
ACS Appl Mater Interfaces ; 15(8): 10761-10773, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36786765

RESUMO

Hydrogenation of naphthalene can effectively reduce the content of aromatics in oil and generate high-value products. A series of Pt-based aluminum-modified core-shell-structured hierarchically periodic mesoporous organosilica@mesoporous silica nanoparticles (Pt/Al-x-PMOs@MSNs) were successfully synthesized and tested for the hydrogenation properties, with preferable mass transfer of macromolecular reactants in the pores and increasing the total acidity of the catalysts. Moreover, the physicochemical properties of the core-shell-structured Pt-based catalysts were systematically analyzed using various characterization techniques. At 300 °C, the naphthalene conversion on the Pt/Al-10-PMOs@MSNs catalyst reached up to 100%, the selectivity of trans-decalin reached 83.9%, and the rate constants (k1, k2) and TOF were 13.2 × 10-6 mol·g-1·s-1, 1.7 × 10-7 mol·g-1·s-1, and 218.8 h-1, respectively. In the presence of sulfur, the naphthalene hydrogenation over the Pt/Al-10-PMOs@MSN catalyst first decreased to around 40% and then recovered to the original level, which originated from the synergistic effect of the texture and chemical properties over the Pt/Al-10-PMOs@MSNs with an excellent performance.

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