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1.
Nanoscale Adv ; 5(11): 3053-3062, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37260491

RESUMO

The combination of chemotherapy with photothermal therapy (PTT) has attracted extensive attention due to its excellent synergetic effect attributing to the fact that hyperthermia can effectively promote the tumor uptake of chemotherapeutic drugs. Herein, we propose a light-initiated gold nanoparticle (AuNP) aggregation boosting the uptake of chemotherapeutic drugs for enhanced chemo-photothermal tumor therapy. Novel light-responsive AuNPs (tm-AuNPs) were rationally designed and fabricated by conjugating both 2,5-diphenyltetrazole (Tz) and methacrylic acid (Ma) onto the surface of AuNPs with small size (∼20 nm). Upon the irradiation of 405 nm laser, AuNPs could be initiated to form aggregates specifically within tumors through the covalent cycloaddition reaction between Tz and Ma. Taking advantage of the controllable photothermal effect of Au aggregates under NIR excitation, improved enrichment of doxorubicin (DOX) in tumor tissues was realized, combined with PTT, resulting in outstanding synergetic anti-tumor efficacy in living mice. We thus believe that this light-initiated AuNP aggregation approach would offer a valuable and powerful tool for precisely synergistic chemo-photothermal tumor therapy.

2.
Hell J Nucl Med ; 25(2): 205-209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35913867

RESUMO

Hepatic epithelioid angiomyolipoma (HEAML) is a rare hepatic mesenchymal tumor with malignant potential. Unlike hepatic angiomyolipoma, HEAML is devoid of adipocytes. Thus, it is easy to be misdiagnosed as other tumors of liver, especially hepatocellular carcinoma (HCC) on preoperative imaging examinations. Herein, we present a case of HEAML mimicking HCC on magnetic resonance (MR) and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in a 50-year-old female. After the primary diagnosis of HCC, the patient underwent a laparoscopic resection. The histopathology and immunohistochemical staining helped to reach the final diagnosis of HEAML. The important sign of central vessel can be seen on MRI in this case. The average apparent diffusion coefficient (ADC) value of the HEAML is 0.86±0.13x10-3mm2/s, which is lower than that of 0.97±0.02?10-3mm2/s of the normal liver. Previous literature on 18F-FDG PET/CT imaging of HEAML is limited to only 2 cases. The 18F-FDG PET/CT images of HEAML with high 18F-FDG accumulation with a maximum standardized uptake value (SUVmax) of 8.88 and extensive necrosis are presented, indicating its malignant potential. This case aims to improve the ability of differential diagnosis from HCC on multimodal imaging, and provides values for further 18F-FDG PET/CT related studies.


Assuntos
Angiomiolipoma , Carcinoma Hepatocelular , Neoplasias Hepáticas , Feminino , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos
3.
Viruses ; 13(12)2021 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-34960652

RESUMO

Murine hepatitis virus strain A59 (MHV-A59) was shown to induce pyroptosis, apoptosis, and necroptosis of infected cells, especially in the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59 is unknown. We utilized murine macrophages and a C57BL/6 mice intranasal infection model to address this. In primary macrophages, the ferroptosis inhibitor inhibited viral propagation, inflammatory cytokines released, and cell syncytia formed after MHV-A59 infection. In the mouse model, we found that in vivo administration of liproxstatin-1 ameliorated lung inflammation and tissue injuries caused by MHV-A59 infection. To find how MHV-A59 infection influenced the expression of ferroptosis-related genes, we performed RNA-seq in primary macrophages and found that MHV-A59 infection upregulates the expression of the acyl-CoA synthetase long-chain family member 1 (ACSL1), a novel ferroptosis inducer. Using ferroptosis inhibitors and a TLR4 inhibitor, we showed that MHV-A59 resulted in the NF-kB-dependent, TLR4-independent ACSL1 upregulation. Accordingly, ACSL1 inhibitor Triacsin C suppressed MHV-A59-infection-induced syncytia formation and viral propagation in primary macrophages. Collectively, our study indicates that ferroptosis inhibition protects hosts from MHV-A59 infection. Targeting ferroptosis may serve as a potential treatment approach for dealing with hyper-inflammation induced by coronavirus infection.


Assuntos
Coenzima A Ligases/antagonistas & inibidores , Coenzima A Ligases/metabolismo , Infecções por Coronavirus/terapia , Ferroptose , Animais , Coenzima A Ligases/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Genes Virais , Lesão Pulmonar/patologia , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Vírus da Hepatite Murina , Quinoxalinas , Células RAW 264.7 , Compostos de Espiro , Receptor 4 Toll-Like , Replicação Viral/genética
4.
Anal Chem ; 93(26): 9277-9285, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34160212

RESUMO

Specific and effective accumulation of nanoparticles within tumors is highly crucial for precise cancer diagnosis and treatment. Therefore, spatiotemporally manipulating the aggregation of small gold nanoparticles (AuNPs) in a tumor microenvironment is of great significance for enhancing the diagnostic and therapeutic efficacy of tumors. Herein, we reported a novel furin enzyme/acidic pH synergistically triggered small AuNP aggregation strategy for activating the photoacoustic (PA) imaging and photothermal (PTT) functions of AuNPs in vivo. Smart gold nanoparticles decorated with furin-cleavable RVRR (Arg-Val-Arg-Arg) peptides (Au-RRVR) were rationally designed and fabricated. Both in vitro and in vivo experiments demonstrated that such Au-RRVR nanoparticles could be simultaneously induced by furin and acidic pH to form large aggregates within tumorous tissue resulting in improved tumor accumulation and retention, which can further activate the PA and PTT effect of AuNPs for sensitive imaging and efficient therapy of tumors. Thus, we believe that this dual-stimuli-responsive aggregation system may offer a universal platform for effective cancer diagnosis and treatment.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Linhagem Celular Tumoral , Furina , Ouro , Humanos , Concentração de Íons de Hidrogênio , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia , Terapia Fototérmica , Microambiente Tumoral
5.
iScience ; 24(3): 102169, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33665583

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, characterized by relapsing and remitting colon mucosal inflammation. For patients suffering from UC, a higher risk of colon cancer has been widely recognized. Here, we found that Elf4 -/- mice developed colon tumors with 3 cycles of dextran sulfate sodium salt (DSS) treatment alone. We further showed that ELF4 suppression was prevalent in both patients with UC and DSS-induced mice models, and this suppression was caused by promoter region methylation. ELF4, upon PARylation by PARP1, transcriptionally regulated multiple DNA damage repair machinery components. Consistently, ELF4 deficiency leads to more severe DNA damage both in vitro and in vivo. Oral administration of montmorillonite powder can prevent the reduction of ELF4 in DSS-induced colitis models and lower the risk of colon tumor development during azoxymethane (AOM) and DSS induced colitis-associated cancer (CAC). These data provided additional mechanism of CAC initiation and supported the "epigenetic priming model of tumor initiation".

6.
Nanomedicine (Lond) ; 14(22): 2941-2955, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31755353

RESUMO

Aim: We aimed to characterize the tumor-targeting and radiosensitization properties of the photo-responsive gold nanoparticles (AuNPs) decorated photolabile diazirine group and folic acid for improved radiotherapy and computed tomography imaging of tumors. Methods: Folic acid and photolabile diazirine group were covalently conjugated on the surface of AuNPs to afford the desired photo-responsive dAuNP-FA (AuNPs capped with poly(ethylene) glycol ligands bearing photolabile diazirine group and folic acid). The probes were intravenously injected into tumor-bearing mice followed by photocrosslinking upon 405 nm laser irradiation for radiotherapy and computed tomography imaging of tumors in vivo. Results: Light-triggered crosslinking of AuNPs in vivo remarkably enhanced the accumulation and retention of AuNPs within tumors. Conclusion: We have successfully developed a novel photo-responsive Au particle-based tumor theranostic probe showing remarkably improved tumor targeting ability and radiosensitization effect.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Radiossensibilizantes/química , Tomografia Computadorizada por Raios X/métodos , Animais , Divisão Celular/genética , Divisão Celular/fisiologia , Linhagem Celular Tumoral , Feminino , Ácido Fólico/química , Fase G2/genética , Fase G2/fisiologia , Humanos , Camundongos , Polietilenoglicóis/química
7.
J Am Chem Soc ; 141(7): 3265-3273, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30689382

RESUMO

The abnormal expression of tumor-related proteases plays a critical role in cancer invasion, progression, and metastasis. Therefore, it is considerably meaningful to non-invasively assess the proteases' activity in vivo for both tumor diagnosis and therapeutic evaluation. Herein, we report an activatable probe constructed with a near-infrared dye (Cy5.5) and a quencher (QSY21) covalently linked through a peptide substrate of matrix metalloproteinases-2 (MMP-2) that was chosen as a model for tumor-associated proteases. Upon cleavage with activated MMP-2, this probe emitted an MMP-2-concentration-dependent fluorescence. Quite unexpectedly, owing to the variation in the aggregation state of both the dye and its quencher as a consequence of the cleavage, the responsive probe presented a dramatic MMP-2-concentration-dependent absorption at around 680 nm, while that at around 730 nm was MMP-2 concentration independent. These features allowed detection of MMP-2 activity via both fluorescence and photoacoustic (PA) imaging in vitro, respectively. Moreover, taking the PA signal at 730 nm as an internal reference, the PA signal at 680 nm allowed quantitative detection of MMP-2 expression in breast cancer in vivo. We thus envision that our current approach would offer a useful tool for studying the malignant impacts of versatile tumor-associated proteases in vivo.


Assuntos
Corantes Fluorescentes/química , Metaloproteinase 2 da Matriz/análise , Animais , Carbocianinas/química , Linhagem Celular Tumoral , Feminino , Fluorescência , Neoplasias Mamárias Animais/diagnóstico por imagem , Camundongos Endogâmicos BALB C , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Nucleotídeos/química , Técnicas Fotoacústicas/métodos , Rodaminas/química
8.
Chembiochem ; 20(5): 667-671, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30447100

RESUMO

Manipulating the cross-coupling of gold nanoparticles (AuNPs) to maximize the photothermal effect is a promising strategy for cancer therapy. Here, by taking advantage of the well-known tetrazole/alkene photoclick chemistry, we have demonstrated for the first time that small AuNPs (23 nm) decorated with both 2,5-diphenyltetrazole and methacrylic acid on their surfaces can form covalently crosslinked aggregates upon laser irradiation (λ=405 nm). In vitro studies indicated that the light-triggered assembling shifted the surface plasmon resonance of AuNPs significantly to near-infrared (NIR) regions, which as a consequence effectively enhanced the efficacy of photothermal therapy for 4T1 breast cancer cells. We thus believe that this new light-triggered cross-coupling approach might offer a valuable tool for cancer treatment.


Assuntos
Ouro/uso terapêutico , Hipertermia Induzida/métodos , Nanopartículas Metálicas/uso terapêutico , Neoplasias/tratamento farmacológico , Fototerapia/métodos , Células 3T3 , Animais , Linhagem Celular Tumoral , Metacrilatos/química , Camundongos , Ressonância de Plasmônio de Superfície , Tetrazóis/química
9.
Nanoscale ; 10(43): 20126-20130, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30376027

RESUMO

Computed tomography (CT) is one of the most frequently used diagnostic imaging modalities in clinics. However, the fast clearance of CT contrast agents through the kidney and short circulation time severely restrict their in vivo applications. Herein, taking advantage of the biocompatible CBT condensation reaction, we rationally designed and synthesized a new smart acidic pH/glutathione (GSH) dual-stimuli responsive nanoprobe (1) which can intermolecularly undergo condensation and form a nanoparticle assembly (I-NPs) in the tumour microenvironment. In vivo CT imaging results indicated that probe 1 could be successfully applied for enhanced CT imaging of tumours in nude mice with a low dose of 21.79 mg I per kg body weight, which may offer a promising tool for precise tumor diagnosis.


Assuntos
Meios de Contraste/química , Nanopartículas/química , Neoplasias/diagnóstico , Tomografia Computadorizada por Raios X , Animais , Linhagem Celular Tumoral , Glutationa/química , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Nus , Microscopia Confocal , Neoplasias/diagnóstico por imagem , Oxirredução , Transplante Heterólogo
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