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1.
Nanoscale ; 13(45): 19085-19097, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34761764

RESUMO

Polypyrrole (PPy) nanoparticles have been widely studied in tumor photothermal therapy (PTT) for their significant photostability, good biocompatibility, and excellent photothermal performance. Herein, we report bovine serum albumin (BSA) stabilized PPy that were mineralized by MnO2 nanozyme on the surface (PPy@BSA-MnO2) to achieve synergistic photothermal and chemodynamic therapy (CDT) for breast cancer. In this multifunctional nanoplatform, the surface-loaded MnO2 undergoes a redox reaction with glutathione (GSH) to generate glutathione disulfide (GSSG) and Mn2+. Then, Mn2+ can convert H2O2 into a highly cytotoxic ˙OH to achieve chemodynamic therapy (CDT) and possess good magnetic resonance (MR) T1-weighted imaging capabilities to realize contrast imaging of the 4T1 tumor-bearing mouse models. In addition, PPy nanoparticles can efficiently convert near-infrared light energy into heat and achieve PTT. Most importantly, PPy@BSA-MnO2 nanoprobes have excellent in vitro 4T1 cell-killing effect and in vivo tumor-suppressive properties. The acute toxicity assessment results indicate that PPy@BSA-MnO2 nanoprobes have good biological safety. Therefore, the as-prepared multifunctional PPy@BSA-MnO2 nanoprobes possess excellent performance to promote MRI-guided PTT/CDT synergistic therapy for breast cancer treatment and have extensive clinical transformation and application prospects.


Assuntos
Neoplasias , Polímeros , Animais , Peróxido de Hidrogênio , Imageamento por Ressonância Magnética , Compostos de Manganês , Camundongos , Óxidos , Pirróis , Nanomedicina Teranóstica
2.
Adv Mater ; 33(37): e2102054, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34309925

RESUMO

Arsenical drugs have achieved hallmark success in treating patients with acute promyelocytic leukemia, but expanding their clinical utility to solid tumors has proven difficult with the contradiction between the therapeutic efficacy and the systemic toxicity. Here, leveraging efforts from materials science, biocompatible PEGylated arsenene nanodots (AsNDs@PEG) with high monoelemental arsenic purity that can selectively and effectively treat solid tumors are synthesized. The intrinsic selective killing effect of AsNDs@PEG is closely related to high oxidative stress in tumor cells, which leads to an activated valence-change of arsenic (from less toxic As0 to severely toxic oxidation states), followed by decreased superoxide dismutase activity and massive reactive oxygen species (ROS) production. These effects occur selectively within cancer cells, causing mitochondrial damage, cell-cycle arrest, and DNA damage. Moreover, AsNDs@PEG when applied in a multi-drug combination strategy with ß-elemene, a plant-derived anticancer drug, achieves synergistic antitumor outcomes, and its newly discovered on-demand photothermal properties facilitate the elimination of the tumors without recurrence, potentially further expanding its clinical utility. In line of the practicability for a large-scale fabrication and negligible systemic toxicity of AsNDs@PEG (even at high doses and with repetitive administration), a new-concept arsenical drug with high therapeutic efficacy for selective solid tumor therapy is provided.

3.
J Appl Toxicol ; 41(6): 941-952, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33094530

RESUMO

Cerium oxide (CeO2 ) nanoparticles have unique redox properties and exert excellent antioxidant effects in the biological environment. In recent years, many researchers have focused on the CeO2 nanoparticles as an effective antioxidant drug in the prevention and treatment of various diseases. However, the toxicity of CeO2 nanoparticles in vivo remains controversial and still needs intensive research. Therefore, the objective of this study is to investigate the pulmonary and systemic toxicity in rats after 14 days of exposure to the PEGylated CeO2 nanoparticles (abbreviated as CNPs; exposure dose of 2, 10, or 20 mg/kg) through a single intratracheal instillation (IT). We assessed the indicators of lung injury and the pathological damage degree of lung tissue. The bronchoalveolar lavage fluid (BALF) analysis and lung histopathology revealed the occurrence of slight pulmonary inflammation in the 20-mg/kg experimental group rats. However, the inflammation factors in the lung tissue of every group rats did not significantly increase, and the levels of superoxide dismutase (SOD) and glutathione (GSH) in lung tissue homogenate rose considerably in the experimental groups. Collectively, these results indicated that pulmonary exposure by the high dose of CNPs could induce mild pulmonary inflammation but did not cause severe systemic toxicity. Moreover, we speculate that the mechanism of pulmonary toxicity of CNPs in rats was due to the autophagic death of healthy lung epithelial cells mediated by endoplasmic reticulum stress. Our results implicate that CNPs can be safely used as an antioxidant drug for the oxidative stress pulmonary diseases.

4.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(1): 62-66, 2020 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-32476374

RESUMO

OBJECTIVE: To investigate the effects of cerium oxide (CeO2) nanoparticles on the viabilities of nerve cells PC12 and SH-SY5Y. METHODS: CeO2 nanoparticles were synthesized, structures were characterized and properties were evaluated. PC12 cells and SH-SY5Y cells were treated with CeO2 nanoparticles at different concentrations (1, 2.5, 5, 10, 25, 50, 75, 100, 150 µg/ml) for 24 h and the cell viability was measured by MTT assay. Then PC12 cells and SH-SY5Y cells were co-treated with CeO2 and active oxygen scavenger NAC and the cells were stained with DCFH-DA probe for ROS. The number of cells and the fluorescence intensity were observed under a fluorescent inverted microscope. Differences were assessed by one-way ANOVA. RESULTS: After treatment with CeO2 nanoparticles, the viabilities of both PC12 cells (P<0.01) and SH-SY5Y cells (P<0.01) were decreased comparing with the control group. After staining with DCFH-DA probe, the fluorescence intensity of the nerve cells was enhanced depending on the concentration of CeO2 nanoparticles suggesting that CeO2 induced the generation of reactive oxygen species (ROS). The fluorescence intensity of PC12 cells was decreased after CeO2 nanoparticles (100 µg/ml) co-treatment with active oxygen scavenger NAC. Compared with CeO2 nanoparticles alone at 25 µg/ml (P<0.01), 50 µg/ml (P<0.01), 75 µg/ml (P<0.01), 100 µg/ml (P<0.01), the cell viability was significantly increased after co-treatment with NAC. CONCLUSION: CeO2 nanoparticles has a negative effect on the viabilities of nerve cells PC12 and SH-SY5Y, and the effect might be depend on ROS.


Assuntos
Sobrevivência Celular , Cério/farmacologia , Nanopartículas , Neurônios/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Humanos , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo
5.
Adv Healthc Mater ; 9(1): e1900948, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746549

RESUMO

Prussian blue nanoprobes are widely studied and applied in tumor photothermal therapy (PTT) and magnetic resonance imaging (MRI), due to their low toxicity and excellent in vivo performance. However, the sizes of hitherto reported Prussian blue nanoprobes are generally larger than 50 nm, which greatly influence cell phagocytosis, in vivo circulation, and biodistribution. In this work, a novel method of doping zinc ions is used to control the size of Prussian blue nanoprobes. Consequently, the performances of the nanoprobes in PTT and MRI are both significantly improved. The results show that the minimum size of Prussian blue nanoprobes achieved by doping 10% zinc ions (abbreviated as SPBZn(10%)) is 3.8 ± 0.90 nm, and the maximum specific absorption coefficient, photothermal conversion efficiency, and longitudinal relaxation rates are 1.78 L g-1 cm-1 , 47.33%, and 18.40 mm-1 s-1 , respectively. In addition, the SPBZn(10%) nanoprobes provide excellent PTT efficacy on 4T1 tumor cells (killing rate: 90.3%) and breast cancer model (tumor inhibition rate: 69.4%). Toxicological experiment results show that the SPBZn(n%) nanoprobes exhibit no obvious in vitro cytotoxicity and they can be used safely in mice at doses below 100 mg kg-1 . Therefore, SPBZn(10%) nanoprobes can potentially be used for effective cancer theranostics.


Assuntos
Neoplasias da Mama/terapia , Ferrocianetos/química , Nanoestruturas/química , Fármacos Fotossensibilizantes/química , Terapia Fototérmica/métodos , Zinco/química , Animais , Neoplasias da Mama/diagnóstico por imagem , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Hipertermia Induzida , Raios Infravermelhos , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Nanomedicina Teranóstica , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
6.
J Toxicol Sci ; 44(9): 621-632, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474743

RESUMO

In the past few decades, upconversion nanoparticles (abbreviated as UCNPs) have been more widely applied in the biomedical fields, such as in vitro and in vivo upconversion fluorescent bioimaging, photodynamic therapy, biological macromolecular detection, imaging mediated drug delivery and so on. But meanwhile, there is still not much research on the acute toxicity of upconversion nanoparticles in vivo, such as acute hepatotoxicity. In this work, we studied the in vivo biodistribution and acute hepatotoxicity of multimodal targeted contrast agent NaLuF4:Gd,Yb,Er-PEG/PEI-FA nanoprobe, which were synthesized by the solvothermal method and modified with Polyethylene glycol (PEG), Polyetherimide (PEI), folic acid (FA) on the surface. The acute hepatotoxicity in mice was systematically assessed after tail vein injection of different concentration of UCNPs. The results showed that NaLuF4:Gd,Yb,Er-PEG/PEI-FA nanoparticles with an average diameter of 44.5 ± 10.4 nm, and three typical upconversion fluorescence emission bands at 520 nm, 540 nm and 660 nm under the excitation of 980 nm laser. In vivo distribution experiments results demonstrated that approximately 87% of UCNPs injected through the tail vein accumulate in the liver. In the acute hepatotoxicity test, the intravenously injection dose of UCNPs was 10, 40, 70 and 100 mg/kg, respectively. The body weight, blood routine, serum biochemistry, histomorphology and liver oxidative stress were detected and observed no significant acute hepatotoxicity damage under the injection dose of 100 mg/kg. In conclusion, NaLuF4:Gd,Yb,Er-PEG/PEI-FA nanoprobes are safe and reliable, and have potential applications in the field of tumor targeted multimodal imaging.


Assuntos
Meios de Contraste/toxicidade , Corantes Fluorescentes/toxicidade , Gadolínio/toxicidade , Fígado/efeitos dos fármacos , Fígado/diagnóstico por imagem , Imagem Multimodal/métodos , Nanopartículas/efeitos adversos , Animais , Meios de Contraste/administração & dosagem , Meios de Contraste/metabolismo , Relação Dose-Resposta a Droga , Feminino , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/metabolismo , Gadolínio/administração & dosagem , Gadolínio/metabolismo , Injeções Intravenosas , Camundongos Endogâmicos ICR , Nanopartículas/administração & dosagem , Nanopartículas/metabolismo , Tamanho da Partícula , Segurança , Distribuição Tecidual
7.
Nano Lett ; 19(8): 5674-5682, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31361142

RESUMO

The efficiency of chemical intercommunication between enzymes in natural networks can be significantly enhanced by the organized catalytic cascades. Nevertheless, the exploration of two-or-more-enzymes-engineered nanoreactors for catalytic cascades remains a great challenge in cancer therapy because of the inherent drawbacks of natural enzymes. Here, encouraged by the catalytic activity of the individual nanozyme for benefiting the treatment of solid tumors, we propose an organized in situ catalytic cascades-enhanced synergistic therapeutic strategy driven by dual-nanozymes-engineered porphyrin metal-organic frameworks (PCN). Precisely, catalase-mimicking platinum nanoparticles (Pt NPs) were sandwiched by PCN, followed by embedding glucose oxidase-mimicking ultrasmall gold nanoparticles (Au NPs) within the outer shell, and further coordination with folic acid (P@Pt@P-Au-FA). The Pt NPs effectively enabled tumor hypoxia relief by catalyzing the intratumoral H2O2 to O2 for (1) enhancing the O2-dependent photodynamic therapy and (2) subsequently accelerating the depletion of ß-d-glucose by Au NPs for synergistic starving-like therapy with the self-produced H2O2 as the substrate for Pt NPs. Consequently, a remarkably strengthened antitumor efficiency with prevention of tumor recurrence and metastasis was achieved. This work highlights a rationally designed tumor microenvironment-specific nanoreactor for opening improved research in nanozymes and provides a means to design a catalytic cascade model for practical applications.


Assuntos
Ouro/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Neoplasias/tratamento farmacológico , Platina/uso terapêutico , Porfirinas/uso terapêutico , Animais , Linhagem Celular Tumoral , Humanos , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/ultraestrutura , Camundongos , Neoplasias/patologia , Fotoquimioterapia
8.
Small ; 14(35): e1801851, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30058139

RESUMO

AuroShell nanoparticles (sealed gold nanoshell on silica) are the only inorganic materials that are approved for clinical trial for photothermal ablation of solid tumors. Based on that, porous gold nanoshell structures are thus critical for cancer multiple theranostics in the future owing to their inherent cargo-loading ability. Nevertheless, adjusting the diverse experimental parameters of the reported procedures to obtain porous gold nanoshell structures is challenging. Herein, a series of amino-functionalized porous metal-organic frameworks (NH2 -MOFs) nanoparticles are uncovered as superior templates for porous gold nanoshell deposition (NH2 -MOFs@Aushell ) by means of a more facile and general one-step method, which combines the enriched functionalities of NH2 -MOFs with those of porous gold nanoshells. Moreover, in order to illustrate the promising applications of this method in biomedicine, platinum nanozymes-encapsulated NH2 -MOFs are further designed with porous gold nanoshell coating and photosensitizer chlorin e6 (Ce6)-loaded nanoparticles with continuous O2 -evolving ability (Pt@UiO-66-NH2 @Aushell -Ce6). The combination of photodynamic and photothermal therapy is then carried out both in vitro and in vivo, achieving excellent synergistic therapeutic outcomes. Therefore, this work not only presents a facile strategy to fabricate functionalized porous gold nanoshell structures, but also illustrates an excellent synergistic tumor therapy strategy.


Assuntos
Ouro/química , Estruturas Metalorgânicas/química , Nanoconchas/química , Neoplasias/terapia , Animais , Terapia Combinada , Humanos , Células MCF-7 , Estruturas Metalorgânicas/ultraestrutura , Camundongos , Nanoconchas/ultraestrutura , Porosidade , Temperatura
9.
Nanoscale ; 10(36): 17038-17052, 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-29850734

RESUMO

Achieving efficient photodynamic therapy (PDT) in deeper biological tissue is still the biggest bottleneck that limits its widespread application in clinic. Although deeper biological tissue PDT could be realized through a combination of upconversion nanoparticles with a photosensitizer, issues with particle-size-induced upconversion fluorescence (UF) reduction and the related in vivo toxicity still cannot be solved properly. In this study, we synthesized Y1Rs-ligand [Pro30, Nle31, Bpa32, Leu34]NPY(28-36) (NPY)-modified and photosensitizer MC540-loaded LiLuF4:Yb,Er@nLiGdF4@mSiO2 multifunctional nanocomposites (MNPs) with a core-multishell structure and ultrasmall size. Their in vitro and in vivo breast tumor targeting, trimodality imaging performance, PDT therapeutic efficacy, and acute toxicity were evaluated. Our results demonstrated that the core-multishell MNPs(MC540) could achieve excellent UF imaging, and that doping with Gd3+ and Lu3+ rare earth ions could enhance the MR and CT imaging performance. In addition, the mSiO2 shell provided a higher loading rate for the photosensitizer MC540, and the DSPE-PEG thin layer coating outside the MNPs(MC540) further improved the water solubility and biocompatibility, reducing the acute toxicity of the nanocomposites. Finally, the NPY modification enhanced the targetability of MNPs(MC540)/DSPE-PEG-NPY to breast tumors, improving the trimodality UF, CT, and MR imaging performance and PDT efficacy for Y1-receptor-overexpressed breast cancer. In general, our developed multifunctional nanocomposites can serve as a theranostic agent with low toxicity, providing great potential for their use in clinical breast cancer diagnosis and therapy.


Assuntos
Nanocompostos/química , Neoplasias Experimentais/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Nanopartículas/química , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Small ; 14(19): e1800094, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29655279

RESUMO

Gold nanoparticle (AuNP) assemblies (GNAs) have attracted attention since enhanced coupling plasmonic resonance (CPR) emerged in the nanogap between coupling AuNPs. For one dimensional GNAs (1D-GNAs), most CPR from the nanogaps could be easily activated by electromagnetic waves and generate drastically enhanced CPR because the nanogaps between coupling AuNPs are linearly distributed in the 1D-GNAs. The reported studies focus on the synthesis of 1D-GNAs and fundamental exploration of CPR. There are still problems which impede further applications in nanomedicine, such as big size (>500 nm), poor water solubility, and/or poor stability. In this study, a kind of 1D flexible caterpillar-like GNAs (CL-GNAs) with ultrasmall nanogaps, good water solubility, and good stability is developed. The CL-GNAs have a flexible structure that can randomly move to change their morphology, which is rarely reported. Numerous ultrasmall nanogaps (<1 nm) are linearly distributed along the structure of CL-GNAs and generate enhanced CPR. The toxicity assessments in vitro and vivo respectively demonstrate that CL-GNAs have a low cytotoxicity and good biocompatibility. The CL-GNAs can be used as an efficient photothermal agent for photothermal therapy, a probe for Raman imaging and photothermal imaging.


Assuntos
Diagnóstico por Imagem , Ouro/química , Hipertermia Induzida , Nanopartículas Metálicas/química , Fototerapia , Animais , Feminino , Humanos , Células MCF-7 , Nanopartículas Metálicas/ultraestrutura , Camundongos Nus , Soroalbumina Bovina/química , Análise Espectral Raman
11.
J Mater Chem B ; 6(10): 1449-1451, 2018 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32254208

RESUMO

A new hemicyanine-based fibroblast activation protein-targeted near-infrared fluorescent probe is designed and it shows high selectivity and sensitivity to cancer cell detection, and in vitro and in vivo imaging. This probe is successfully applied in fluorescence detection of living cells (with a detection limit of 1500 cells per mL). It is believed that many new functions or distributions of FAP could be discovered by this new probe later.

12.
J Biomater Appl ; 28(2): 232-40, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22532407

RESUMO

Fluorescence imaging technique has been used for imaging of biological cells and tissues in vivo. The Cd-free luminescent quantum dots conjugating with a cancer targeting ligand has been taken as a promising biocompatibility and low cytotoxicity system for targeted cancer imaging. This work reports the synthesis of fluorescent-doped core/shell quantum dots of water-soluble manganese-doped zinc sulfide. Quantum dots of manganese-doped zinc sulfide were prepared by nucleation doping strategy, with 3-mercaptopropionic acid as stabilizer at 90 in aqueous solution. The manganese-doped zinc sulfide nanoparticles exhibit strong orange fluorescence under UV irradiation, resistance to photo-bleaching, and low-cytotoxicity to HeLa cells. The structure and optical properties of nanoparticles were characterized by scanning electron microscope, X-ray diffraction, dynamic light scattering, and photoluminescence emission spectroscopy. Manganese-doped zinc sulfide nanoparticles conjugated with folic acid using 2,2'-(ethylenedioxy)-bis-(ethylamine) as the linker. The covalent binding of both 2,2'-(ethylenedioxy)-bis-(ethylamine) and folic acid on the surface of manganese-doped zinc sulfide nanoparticles probed by Fourier transform infrared spectroscopy detection. Furthermore, in vitro cytotoxicity assessment of manganese-doped zinc sulfide-folic acid probes use HeLa cells. The obtained fluorescent probes (manganese-doped zinc sulfide) were used for tumor targeting and imaging in vivo. The manganese-doped zinc sulfide-folic acid fluorescent probes which targeting the tumor cells in the body of nude mouse tumor model would emit orange fluorescence, when exposed to a 365 nm lamp. We investigate the biodistribution of the manganese-doped zinc sulfide-folic acid fluorescent probes in tumor mouse model by measuring zinc concentration in tissues. These studies demonstrate the practicality of manganese-doped zinc sulfide-folic acid fluorescent probes as promising platform for tumor targeting and imaging in vivo.


Assuntos
Corantes Fluorescentes , Manganês , Nanopartículas , Neoplasias/diagnóstico , Sulfetos , Compostos de Zinco , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Corantes Fluorescentes/análise , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Manganês/análise , Manganês/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Nanopartículas/análise , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Imagem Óptica , Sulfetos/análise , Sulfetos/toxicidade , Compostos de Zinco/análise , Compostos de Zinco/toxicidade
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