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1.
Nat Commun ; 13(1): 4567, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931744

RESUMO

Inefficient tumour treatment approaches often cause fatal tumour metastases. Here, we report a biomimetic multifunctional nanoplatform explicitly engineered with a Co-based metal organic framework polydopamine heterostructure (MOF-PDA), anethole trithione (ADT), and a macrophage membrane. Co-MOF degradation in the tumour microenvironment releases Co2+, which results in the downregulation of HSP90 expression and the inhibition of cellular heat resistance, thereby improving the photothermal therapy effect of PDA. H2S secretion after the enzymatic hydrolysis of ADT leads to high-concentration gas therapy. Moreover, ADT changes the balance between nicotinamide adenine dinucleotide/flavin adenine dinucleotide (NADH/FAD) during tumour glycolysis. ATP synthesis is limited by NADH consumption, which triggers a certain degree of tumour growth inhibition and results in starvation therapy. Potentiated 2D/3D autofluorescence imaging of NADH/FAD is also achieved in liquid nitrogen and employed to efficiently monitor tumour therapy. The developed biomimetic nanoplatform provides an approach to treat orthotopic tumours and inhibit metastasis.


Assuntos
Materiais Biomiméticos , Hipotermia , Neoplasias , Biomimética , Metabolismo Energético , Flavina-Adenina Dinucleotídeo/metabolismo , Humanos , NAD/metabolismo , Neoplasias/patologia , Microambiente Tumoral
2.
J Colloid Interface Sci ; 621: 77-90, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35452931

RESUMO

Single treatment often faces the problem that it cannot completely eradicate tumor and inhibit the tumor metastasis. In order to overcome this shortcoming, multi-modal tumor treatment has attracted widespread attention. In the present article, based on ascorbyl palmitate (PA) and l-arginine (l-Arg), a multifunctional nanocarrier is designed for synergetic treatment of tumor with photothermal and nitric oxide (NO) gas therapy. Firstly, PA and l-Arg were self-assembled to form novel functional micelles, PL, with high biosafety using electrostatic interaction and hydrogen bonding. The functional micelles could self-catalyze to produce NO at the tumor site. Then, Ag2S quantum dots having fluorescence imaging and photothermal properties were encapsulated to obtain the nanocarrier, A@PL. The results show that A@PL had a hydrated size of around 78 nm and presented good stability within 30 d. Moreover, in vitro studies indicate that it was efficient with regards to NO self-generating capacity, whereas the photothermal conversion efficiency was as high as 34% under near-infrared light irradiation. The cytotoxicity results show that, when the concentration of A@PL was as high as 2 mM, the survival rate of 3 T3 cells was still 78.23%, proving that the probe has good safety characteristics. Fluorescence imaging results show that its maximum enrichment can be achieved at the tumor site after tail vein injection for 3 h, and out of the body after 24 h, indicating good internal circulation. The in vivo studies show that the rate of inhibition of tumor using the nanocarrier was as high as 98%, and almost overcame the problem of tumor recurrence caused by single treatment, thus presenting a significant tumor treatment effect. This new multifunctional nanocarrier with self-catalytic production of NO provides a new idea for the efficient treatment of tumors.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Humanos , Micelas , Neoplasias/terapia , Óxido Nítrico , Imagem Óptica/métodos , Fototerapia/métodos
3.
Nanoscale ; 13(7): 4278-4294, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33595027

RESUMO

Colorectal cancer is one of the malignant tumors with high morbidity and lethality. Its efficient diagnosis and treatment has important significance. In this study, the orthotopic cancer model mouse, which could perfectly simulate clinical inflammatory colorectal cancer, was constructed by chemical induction. Based on this model, a new pH/ultrasonic dual-response, step-targeting and precisely controlled-release enteric-coated granule was designed for the combined sonodynamic (SDT)-chemotherapy. The enteric-coated granule was fabricated by enwrapping carboxymethyl chitosan (CMC) on folic acid-modified phospholipid (SLB-FA) encapsulating mesoporous silicon-coated gold nanoparticles loaded with chlorin (Ce6) and doxorubicin hydrochloride (DOX), titled as Au@mSiO2/Ce6/DOX/SLB-FA@CMC (GMCDS-FA@CMC). The diameter of the Au@mSiO2/Ce6/DOX/SLB-FA (GMCDS-FA) nanoprobe was 61.21 nm and that of the GMCDS-FA@CMC enteric-coated granule was 1.1 µm. MTT results showed that the cell survival rate was still as high as 76.55 ± 1.27% when the concentration of GMCDS-FA was up to 200 µg mL-1, which can indicate the low cytotoxicity of the nanoprobe. According to CT imaging, the enteric-coated granule had the highest concentration in the colorectum of the orthotopic cancer mouse after 7-9 h with oral administration, and was nearly metabolized out of the body after 24 h. The in vitro and in vivo experiments showed that the targeting enteric-coated granule had the best effect of treatment and desired prognosis after combined SDT-chemotherapy.


Assuntos
Neoplasias Colorretais , Nanopartículas Metálicas , Nanopartículas , Animais , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Doxorrubicina/farmacologia , Ácido Fólico , Ouro , Concentração de Íons de Hidrogênio , Camundongos , Ultrassom
4.
ACS Appl Mater Interfaces ; 12(36): 40052-40066, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32806885

RESUMO

Ameliorated therapy based on the tumor microenvironment is becoming increasingly popular, yet only a few methods have achieved wide recognition. Herein, targeting multifunctional hydrophilic nanomicelles, AgBiS2@DSPE-PEG2000-FA (ABS-FA), were obtained and employed for tumor treatment. In a cascade amplification mode, ABS-FA exhibited favorable properties of actively enhancing computed tomography/infrared (CT/IR) imaging and gently relieving ambient oxygen concentration by cooperative photothermal and sonodynamic therapy. Compared with traditional Bi2S3 nanoparticles, the CT imaging capability of the probe was augmented (43.21%), and the photothermal conversion efficiency was increased (33.1%). Furthermore, remarkable ultrasonic dynamic features of ABS-FA were observed, with increased generation of reactive oxygen species (24.3%) being obtained compared to Ce6, a commonly used sonosensitizer. Furthermore, ABS-FA exhibited obvious inhibitory effects on HeLa cell migration at 6 µg/mL, which to some extent, demonstrated its suppressive effect on tumor growth. A lower dose, laser and ultrasonic power, and shorter processing time endowed ABS-FA with excellent photothermal and sonodynamic effects. By mild cascade mode, the hypoxic condition of the tumor site was largely improved, and a suitable oxygen-rich environment was provided, thereby endowing ABS-FA with a superior synergistically enhanced treatment effect compared with the single-mode approach, which ultimately realized the purpose of "one injection, multiple treatment". Moreover, our data showed that ABS-FA was given with a biological safety profile while harnessing in vivo. Taken together, as a synergistically enhanced medical diagnosis and treatment method, the one-for-all nanoplatform will pave a new avenue for further clinical applications.


Assuntos
Antineoplásicos/farmacologia , Ácido Fólico/farmacologia , Neoplasias Experimentais/terapia , Terapia Fototérmica , Compostos de Prata/farmacologia , Sulfetos/farmacologia , Terapia por Ultrassom , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Fólico/química , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/patologia , Tamanho da Partícula , Compostos de Prata/química , Sulfetos/química , Propriedades de Superfície
5.
Biomaterials ; 230: 119636, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31785776

RESUMO

Sonodynamic therapy (SDT) has rapidly developed as a powerful alternative to traditional photodynamic therapy due to its intrinsically deeper tissue-penetration. However, single SDT dose is incapable of radical cure because the long-term hypoxia of tumor limits its therapeutic effect. Herein, we developed a biomimetic nanoplatform with dual pH/ultrasound response, homologous targeting and low phototoxicity for combined nitric oxide (NO) gas therapy with SDT to solve the problem. This nanoplatform is composed of zeolite imidazole framework-8 material embedded with nitrosoglutathione (GSNO) and chlorin e6 (Ce6) by one-step encapsulation, and then wrapped by homologous tumor cell membrane. In vitro and in vivo experiments indicate that the biomimetic nanoplatform has excellent biocompatibility and shows higher retention in tumor by homologous targeting. Importantly, it can sustainably release the encapsulated drug in acidic tumor microenvironment and accelerate degradation by ultrasound (US). Furthermore, NO released from GSNO and reactive oxygen species generated by Ce6, which are both triggered by US, react with each other to produce highly reactive peroxynitrite to inhibit the growth of tumor. Moreover, by repeated US irradiation, the tumor hypoxia can be relieved for a much-longer term, resulting in an effective gas-sonodynamic combined treatment. This study fully utilizes the advantages of US, providing a new strategy for high-performance cancer therapy.


Assuntos
Biomimética , Fotoquimioterapia , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Hipóxia , Óxido Nítrico
6.
Chemistry ; 25(31): 7553-7560, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-30970162

RESUMO

Given their superior penetration depths, photosensitizers with longer absorption wavelengths present broader application prospects in photodynamic therapy (PDT). Herein, Ag2 S quantum dots were discovered, for the first time, to be capable of killing tumor cells through the photodynamic route by near-infrared light irradiation, which means relatively less excitation of the probe compared with traditional photosensitizers absorbing short wavelengths. On modification with polydopamine (PDA), PDA-Ag2 S was obtained, which showed outstanding capacity for inducing reactive oxygen species (increased by 1.69 times). With the addition of PDA, Ag2 S had more opportunities to react with surrounding O2 , which was demonstrated by typical triplet electron spin resonance (ESR) analysis. Furthermore, the PDT effects of Ag2 S and PDA-Ag2 S achieved at longer wavelengths were almost identical to the effects produced at 660 nm, which was proved by studies in vitro. PDA-Ag2 S showed distinctly better therapeutic effects than Ag2 S in experiments in vivo, which further validated the enhanced regulatory effect of PDA. Altogether, a new photosensitizer with longer absorption wavelength was developed by using the hitherto-unexplored photodynamic function of Ag2 S quantum dots, which extended and enhanced the regulatory effect originating from PDA.


Assuntos
Indóis/uso terapêutico , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/uso terapêutico , Pontos Quânticos/uso terapêutico , Compostos de Prata/uso terapêutico , Animais , Feminino , Células HeLa , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Neoplasias/metabolismo , Neoplasias/patologia , Fotoquimioterapia/métodos , Pontos Quânticos/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo
7.
Nanotechnology ; 29(35): 355101, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-29873637

RESUMO

A graphene quantum dot (GQD) is a novel carbon nanomaterial with the advantages of low cost and no pollution. It has attracted serious attention in the biomedical fields because of its stabilities and tunable fluorescence wavelength. In this manuscript, an N-doped graphene quantum dot (N-GQD) was synthesized by a hydrothermal method using citric acid as the carbon source and urea as the nitrogen source. X-ray diffraction, Raman spectroscopy, transmission electron microscopy, UV-vis absorption spectrum, and fluorescence spectrum were used to characterize the N-GQD. The results showed that the N-GQD had a uniform size of about 5 nm. The two fluorescence emission peaks, one in the visible light region showed a 49.75% quantum yield, while another in the near infrared region was 2.49%. The photothermal conversion efficiency was 62.53%, higher than any kind of carbon nanomaterial in existence today. MTT and a long-term cytotoxicity experiment confirmed that the N-GQD had low cytotoxicity. The probe also had the ability of photoacoustic response at the same time. After coupling with folic acid, it presented imaging and photothermal therapy on the cells, which has great application prospects in the early diagnosis and treatment of tumors.


Assuntos
Grafite/química , Luz , Nitrogênio/química , Imagem Óptica/métodos , Pontos Quânticos/química , Temperatura , Células A549 , Adsorção , Ácido Fólico/química , Células HeLa , Humanos , Técnicas Fotoacústicas , Pontos Quânticos/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Propriedades de Superfície , Difração de Raios X
8.
J Nanobiotechnology ; 16(1): 42, 2018 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-29673352

RESUMO

BACKGROUND: Ag2S has the characteristics of conventional quantum dot such as broad excitation spectrum, narrow emission spectrum, long fluorescence lifetime, strong anti-bleaching ability, and other optical properties. Moreover, since its fluorescence emission is located in the NIR-II region, has stronger penetrating ability for tissue. Ag2S quantum dot has strong absorption during the visible and NIR regions, it has good photothermal and photoacoustic response under certain wavelength excitation. RESULTS: 200 nm aqueous probe Ag2S@DSPE-PEG2000-FA (Ag2S@DP-FA) with good dispersibility and stability was prepared by coating hydrophobic Ag2S with the mixture of folic acid (FA) modified DSPE-PEG2000 (DP) and other polymers, it was found the probe had good fluorescent, photoacoustic and photothermal responses, and a low cell cytotoxicity at 50 µg/mL Ag concentration. Blood biochemical analysis, liver enzyme and tissue histopathological test showed that no significant influence was observed on blood and organs within 15 days after injection of the probe. In vivo and in vitro fluorescence and photoacoustic imaging of the probe further demonstrated that the Ag2S@DP-FA probe had good active targeting ability for tumor. In vivo and in vitro photothermal therapy experiments confirmed that the probe also had good ability of killing tumor by photothermal. CONCLUSIONS: Ag2S@DP-FA was a safe, integrated diagnosis and treatment probe with multi-mode imaging, photothermal therapy and active targeting ability, which had a great application prospect in the early diagnosis and treatment of tumor.


Assuntos
Sondas Moleculares , Imagem Óptica/métodos , Técnicas Fotoacústicas/métodos , Pontos Quânticos , Compostos de Prata , Células A549 , Animais , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Sondas Moleculares/química , Sondas Moleculares/toxicidade , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/toxicidade , Fototerapia , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Pontos Quânticos/química , Pontos Quânticos/toxicidade , Compostos de Prata/química , Compostos de Prata/toxicidade
9.
Nanotechnology ; 29(5): 055101, 2018 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-29139396

RESUMO

In this study, an oil-soluble Ag2S quantum dot (QD) was synthesized through thermal decomposition using the single-source precursor method, and Pluronic F127 (PF127), a triblock copolymer functionalized with folic acid (FA), was deposited on the surface of the QD, then a water-soluble PF127-FA@Ag2S nanoprobe with targeting ability was fabricated. The as-prepared PF127-FA@Ag2S exhibited spheroidal morphology and high dispersibility, with average diameters of 115 ± 20.7 nm (as observed by transmission electron microscopy). No obvious toxicity of the PF127-FA@Ag2S nanoprobe was found in standard 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and colony-formation assay, indicating good biocompatibility and safety. The resulting PF127-FA@Ag2S exhibited excellent stability between 4 °C-40 °C. Additionally, the capacity of the tumor cell-targeting high contrast enhanced photoacoustic imaging of PF127-FA@Ag2S was verified in comparison with A547 and HeLa cells. In other words, the excellent properties of PF127-FA@Ag2S show great potential in further research for targeting and photoacoustic imaging.


Assuntos
Ácido Fólico/química , Neoplasias/patologia , Técnicas Fotoacústicas/métodos , Poloxâmero/química , Pontos Quânticos/química , Compostos de Prata/química , Células A549 , Morte Celular , Linhagem Celular Tumoral , Difusão Dinâmica da Luz , Células HeLa , Humanos , Óleos/química , Tamanho da Partícula , Espectroscopia Fotoeletrônica , Pontos Quânticos/ultraestrutura , Solubilidade , Espectrofotometria Ultravioleta , Eletricidade Estática
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