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1.
Appl Opt ; 63(8): 1947-1951, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38568633

RESUMO

Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1, S E S A M 2, and S E S A M 3, respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 1014/c m 2. The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38687850

RESUMO

Objective: Iatrogenic skin injury is a common neonatal skin problem that can have a severe impact on the health and life of newborns. The purpose of this study was to explore the factors influencing iatrogenic skin injury in neonates, identify and correct nursing behaviors that may lead to skin damage, thereby reduce the occurrence of skin damage and protect the health of newborns. Methods: The clinical data of 87 neonates with iatrogenic skin injury admitted to the Department of Neonatology of Shangrao People's Hospital, China, between January and June 2022, were retrospectively collected as a research group. The causes of iatrogenic skin injury were statistically analyzed. 50 neonates without iatrogenic skin injury in the same department during the same period were selected as the control group. The general data of the two groups were contracted, and the independent risk factors affecting iatrogenic skin injury in neonates were explored using multivariate Logistic regression. The corresponding nursing strategies were analyzed. Result: (1) Among the 87 neonates with iatrogenic skin injury, the causes included adhesive dressing stripping (41.38%, 36/87), skin scratch during blue light phototherapy (25.29%, 22/87), diaper dermatitis (20.69%, 18/87), and skin pressure redness related to ventilator and continuous positive airway pressure (CPAP) (12.64%, 11/87). (2) The gestational age, birth weight, length of stay, use of noninvasive mechanical ventilation, orotracheal intubation, gastric tube, PICC catheterization, and skin allergy history of the two groups had statistically significant differences (P < .05). (3) The results of multivariate Logistic regression analysis indicated that the length of stay (OR=2.994, 95% CI=1.341~6.686), orotracheal intubation use (OR=0.015, 95% CI=0.004~0.060), and gastric tube use (OR=17.132, 95% CI=5.231~56.108) were independent risk factors of iatrogenic skin injury in neonates (P < .05). Conclusion: Length of stay, orotracheal intubation use, and gastric tube use are independent risk factors for iatrogenic skin injury in neonates. Hospital stays and unnecessary use of orotracheal intubation and gastric tube should be reduced in future clinical management. Attention should be paid to strengthening skin observation and care, keeping skin dry and clean, and preventing iatrogenic skin injury.

3.
Environ Toxicol ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654487

RESUMO

Proliferative vitreoretinopathy (PVR) is a visual-threatening disease, which cause from the migration of retinal pigment epithelium (RPE). Tricetin, a family of flavonoids, can inhibit the metastasis of several cancers. Herein, we aim to evaluate the possible effect of tricetin on inhibiting ARPE-19 cells migration. The Boyden chamber assay, wound healing assay, RNA sequencing, and Western blot analysis were applied in our experiment. The results revealed that tricetin inhibited the cell migration abilities of ARPE-19 cells. Moreover, using RNA sequencing technology, we revealed that tricetin repressed bone morphogenetic protein-6 (BMP-6) gene expressions in ARPE-19 cells. Overexpression of BMP-6 resulted in significant restoration of cell migration capabilities of tricetin-treated ARPE-19 cells. Furthermore, tricetin suppressed the phosphorylation of the p38 signaling pathway. Moreover, blocking the p38 pathway also inhibits BMP-6 expression and migration in the ARPE-19 cells. In conclusion, this study revealed that tricetin inhibits the ARPE-19 cell migration mainly via the suppression of BMP-6 expression and p38 signaling pathway.

5.
Angew Chem Int Ed Engl ; 62(11): e202218341, 2023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36634030

RESUMO

Metal-free long-wavelength light-driven prodrug photoactivation is highly desirable for applications such as neuromodulation, drug delivery, and cancer therapy. Herein, via triplet fusion, we report on the far-red light-driven photo-release of an anti-cancer drug by coupling the boron-dipyrromethene (BODIPY)-based photosensitizer with a photocleavable perylene-based anti-cancer drug. Notably, this metal-free triplet fusion photolysis (TFP) strategy can be further advanced by incorporating an additional functional dopant, i.e. an immunotherapy medicine inhibiting the indoleamine 2,3-dioxygenase (IDO), with the far-red responsive triplet fusion pair in an air-stable nanoparticle. With this IDO inhibitor-assisted TFP system we observed efficient inhibition of primary and distant tumors in a mouse model at record-low excitation power, compared to other photo-assisted immunotherapy approaches. This metal-free TFP strategy will spur advancement in photonics and biophotonics fields.


Assuntos
Antineoplásicos , Inibidores de Checkpoint Imunológico , Animais , Camundongos , Fotólise , Luz , Imunoterapia , Indolamina-Pirrol 2,3,-Dioxigenase
6.
Chem Eng J ; 441: 136043, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35370448

RESUMO

Disposable surgical masks are widely used by the general public since the onset of the coronavirus outbreak in 2019. However, current surgical masks cannot self-sterilize for reuse or recycling for other purposes, resulting in high economic and environmental costs. To solve these issue, herein we report a novel low-cost surgical mask decorated with copper sulfide (Cu2-xS) nanocrystals for photothermal sterilization in a short time (6 min). With the spun-bonded nonwoven fabrics (SNF) layer from surgical masks as the substrate, Cu2-xS nanocrystals are in-situ grown on their surface with the help of a commercial textile adhesion promoter. The SNF-Cu2-xS layer possesses good hydrophobicity and strong near infrared absorption. Under the irradiation with an infrared baking lamp (IR lamp, 50 mW cm-2), the surface temperature of SNF-Cu2-xS layer on masks can quickly increase to over 78 °C, resulting from the high photothermal effects of Cu2-xS nanocrystals. As a result, the polluted masks exhibit an outstanding antibacterial rate of 99.9999% and 85.4% for the Escherichia coli (E.coli) and Staphylococcus aureus (S. aureus) as well as the inactivation of human coronavirus OC43 (3.18-log10 decay) and influenza A virus A/PR/8/34 (H1N1) (3.93-log10 decay) after 6 min irradiation, and achieve rapid sterilization for reuse and recycling. Therefore, such Cu2-xS-modified masks with IR lamp-driven antibacterial and antiviral activity have great potential for real-time personal protection.

7.
Ecotoxicol Environ Saf ; 238: 113608, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35525112

RESUMO

Hexavalent chromium Cr(VI) is a well-known environmental toxic metal that causes reprotoxicity in pregnant females. There are currently no appropriate interventions or treatments for Cr(VI) exposure during pregnancy. Herein, the protective effect of melatonin (MLT) against Cr(VI)-induced reprotoxicity is investigated by administrating MLT to pregnant mice exposed to Cr(VI). The results indicate that MLT effectively alleviates Cr(VI)-induced adverse pregnancy outcomes, restoring the decreased fetal weight and increased fetal resorption and malformation caused by Cr(VI) exposure to normal levels. MLT reduces the negative effects of Cr(VI) on follicular atresia and the development of primordial follicle in the maternal ovarian, thereby mitigating the decline in the reserve of primordial follicles. MLT alleviates Cr(VI)-induced oxidative stress, hence reducing the excessive accumulation of malondialdehyde in the maternal ovary. MLT inhibits Cr(VI)-induced apoptosis of ovarian granulosa cells and the expression of cleaved caspase-3 in the ovary. MLT reduces the increase in serum follicle-stimulating hormone caused by Cr(VI) exposure, while elevating anti-Mullerian hormone levels. We demonstrate that MLT reverses Cr(VI)-induced reprotoxicity in pregnant mice, opening up a new avenue for treating reproductive defects caused by environmental stress.


Assuntos
Melatonina , Animais , Cromo/metabolismo , Feminino , Atresia Folicular , Melatonina/metabolismo , Melatonina/farmacologia , Camundongos , Ovário , Gravidez , Resultado da Gravidez
8.
Nano Lett ; 21(12): 4903-4910, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34100617

RESUMO

Persistent luminescence nanoparticles (PLNPs) are an emerging photonic nanomaterial that possesses uniquely persistent luminescence properties after excitation ceases. They can be repeatedly recharged in vitro and in vivo and hold great promise for numerous areas and applications. Unfortunately, none of the existing synthesis methods can control their composition to grow core-shell structured PLNPs with desirable shapes and enhanced functionalities. Here, we report on straightforward thermolysis-mediated colloidal synthesis of CaF2:Dy@NaYF4 core-shell PLNPs that can enhance persistent luminescence under both light and X-ray excitations. Benefitting from the well-matched crystal lattices between CaF2 and NaYF4, this colloidal synthesis makes it possible to prepare core-shell PLNPs with exquisite control of the compositions, shapes, and enhanced luminescence. This demonstration of the developing colloidal core-shell PLNPs overcomes the current key bottleneck regarding the synthesis of heterostructured PLNPs and sets the stage for fully exploiting the potential of these fascinating luminous materials.


Assuntos
Nanopartículas , Nanoestruturas , Luminescência
9.
Yi Chuan ; 44(11): 1028-1043, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384995

RESUMO

Han Chinese, Korean and Japanese are the main populations of East Asia, and Han Chinese presents a gradient admixture from north to south. There are differences among the East Asian populations in genetic structure. To achieve fine-scale genetic classification of southern (S-) and northern (N-) Han Chinese, Korean and Japanese individuals in this study, we collected and analyzed 1185 ancestry informative SNPs (AISNPs) from previous literature reports and our laboratory findings. First, two machine learning algorithms, softmax and randomForest, were used to build genetic classification models. Then, phylogenetic tree, STRUCTURE and principal component analysis were used to evaluate the performance of classification for different AISNP panels. The 234-AISNP panel achieved a fine-scale differentiation among the target populations in four classification schemes. The accuracy of the softmax model was 92%, which realized the accurate classification of the S-Han, N-Han, Korean and Japanese individuals. The two machine learning models tested in this study provided important references for the high-resolution discrimination of close-range populations and will be useful tools to optimize marker panels for developing forensic DNA ancestry inference systems.


Assuntos
Povo Asiático , Genética Populacional , Aprendizado de Máquina , Humanos , Japão , Filogenia , República da Coreia , China , Povo Asiático/genética
10.
Exp Eye Res ; 213: 108843, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34793827

RESUMO

Proliferative vitreoretinopathy (PVR) involves retinal pigment epithelium (RPE) cell proliferation and migration and leads to tractional retinal detachment. Demethoxycurcumin (DMC), a curcuminoid, has anti-inflammatory and anti-tumour properties. However, whether DMC affects the migration of RPE cells and the molecular mechanism of human PVR remains unclear. The aim of the current study was to investigate the effects of DMC on the inhibition of migration and proteinase expression of human ARPE-19 cells. Herein, we provided molecular evidence associated with PVR prevention through DMC by inhibiting ARPE-19 cell migration. We performed gelatin zymography, Western blot and RT-PCR and respectively found that DMC is sufficient to reduce matrix metalloproteinase-2 (MMP-2) activity, protein level and mRNA expression. DMC suppressed the nuclear levels of transcriptional factors specificity protein 1 and c-Fos, which are involved in the modulation of the transcriptional activation of the MMP-2 gene. DMC also inhibited STAT-3 phosphorylation in ARPE-19 cells. Selective STAT-3 induction by a STAT-3 activator, colivelin, reverted MMP activity and protein expression and cell migration, which were reduced in response to DMC. The results proved the inhibitory effect of DMC on RPE cell migration and MMP-2 expression by the down-regulation of the STAT-3 signalling pathway.


Assuntos
Movimento Celular/efeitos dos fármacos , Diarileptanoides/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Epitélio Pigmentado da Retina/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Western Blotting , Linhagem Celular , Gelatina/metabolismo , Humanos , Metaloproteinase 2 da Matriz/genética , Fosforilação , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/enzimologia , Transdução de Sinais , Fator de Transcrição Sp1/metabolismo , Cicatrização/efeitos dos fármacos
11.
Development ; 143(7): 1126-33, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26903504

RESUMO

Microtubules play a crucial role in the generation, migration and differentiation of nascent neurons in the developing vertebrate brain. Mutations in the constituents of microtubules, the tubulins, are known to cause an array of neurological disorders, including lissencephaly, polymicrogyria and microcephaly. In this study we explore the genetic and cellular mechanisms that cause TUBB5-associated microcephaly by exploiting two new mouse models: a conditional E401K knock-in, and a conditional knockout animal. These mice present with profound microcephaly due to a loss of upper-layer neurons that correlates with massive apoptosis and upregulation of p53. This phenotype is associated with a delay in cell cycle progression and ectopic DNA elements in progenitors, which is dependent on the dosage of functional Tubb5. Strikingly, we report ectopic Sox2-positive progenitors and defects in spindle orientation in our knock-in mouse line, which are absent in knockout animals. This work sheds light on the functional repertoire of Tubb5, reveals that the E401K mutation acts by a complex mechanism, and demonstrates that the cellular pathology driving TUBB5-associated microcephaly is cell death.


Assuntos
Apoptose/genética , Ciclo Celular/genética , Microcefalia/genética , Microtúbulos/genética , Tubulina (Proteína)/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Encéfalo/anormalidades , Encéfalo/embriologia , Diferenciação Celular , Modelos Animais de Doenças , Embrião de Mamíferos/embriologia , Técnicas de Introdução de Genes , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microtúbulos/metabolismo , Células-Tronco Neurais/citologia , Fatores de Transcrição SOXB1/metabolismo , Fuso Acromático/genética , Células-Tronco/citologia , Proteína Supressora de Tumor p53/biossíntese
12.
Environ Toxicol ; 34(3): 312-318, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30499162

RESUMO

Kaempferol is a flavonoid with anticancer and anti-metastasis activity in different cancer-cell lines. However, the underlying mechanisms by which kaempferol acts on human retinal pigment epithelial (ARPE-19) cells remain unclear. In this study, we demonstrated that kaempferol inhibited migration and invasion in ARPE-19 cells at non-toxic dosages. We discovered that kaempferol obviously reduced the enzyme activity and protein expression of matrix metalloproteinase-2 by increasing the phosphorylated levels of extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathways. Additionally, ERK1/2-specific inhibitor PD98059 significantly reversed kaempferol's inhibitory effects on migration and expression of MMP-2 in ARPE-19 cells. Overall, our results are the first to demonstrate that kaempferol is capable of inhibiting cell migration by targeting ERK1/2 signaling in human retinal pigment epithelial cells.


Assuntos
Movimento Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Quempferóis/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Adulto , Linhagem Celular , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Adulto Jovem
13.
Environ Toxicol ; 33(12): 1298-1303, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30259634

RESUMO

Dihydromyricetin (DHM), a flavanonol compound in Ampelopsis grossedentata, possesses several biological activities. However, the molecular mechanism underlying the effects of DHM on human proliferative vitreoretinopathy (PVR) remains unclear. We explored the effects of DHM on cell migration and the metastasis-promoting proteins in human retinal pigment epithelial (RPE) cells (ARPE-19 cells). Our results revealed that DHM attenuated ARPE-19 cell invasion and migration by reducing matrix metalloproteinase-2 (MMP-2) expression. Furthermore, a Western blot analysis revealed that DHM significantly reduced levels of phosphorylated c-Jun N-terminal kinase 1/2, but not those of extracellular signal-regulated kinase 1/2 and p38. In conclusion, our findings shown that DHM inhibits human RPE cell migration through the inhibition of MMP-2 expression; therefore, DHM may have potential therapeutic value in treating PVR as adjuvant therapy.


Assuntos
Movimento Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Flavonóis/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Retina/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/fisiologia , Humanos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Retina/citologia , Retina/metabolismo , Vitreorretinopatia Proliferativa/metabolismo , Vitreorretinopatia Proliferativa/patologia
14.
J Nanosci Nanotechnol ; 16(6): 5865-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27427645

RESUMO

A prerequisite for the development of photothermal ablation therapy for cancer is to obtain efficient photothermal nanoagents that can be irradiated by near-infrared (NIR) laser. Herein, we have reported the synthesis of WS2 nanowires as photothermal nanoagents by the reaction of WCl6 with CS2 in oleylamine at 280 degrees C. WS2 nanowires have the thickness of -2 nm and length of -100 nm. Importantly, the chloroform dispersion of WS2 nanowires exhibits strong photoabsorption in NIR region. The temperature of the dispersion (0.10-0.50 mg/mL) can increase by 12.8-23.9 degrees C in 5 min under the irradiation of 808 nm laser with a power density of 0.80 W/cm2. Therefore, WS2 nanowires have a great superiority as a new nanoagent for NIR-induced photothermal ablation of cancer, due to their small size and excellent photothermal performance.


Assuntos
Lasers , Nanotecnologia/métodos , Nanofios/química , Fototerapia , Compostos de Tungstênio/química , Raios Infravermelhos
15.
J Biol Chem ; 288(20): 14531-14543, 2013 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-23576431

RESUMO

The development of neuronal polarity is essential for the establishment of the accurate patterning of neuronal circuits in the brain. However, little is known about the underlying molecular mechanisms that control rapid axon elongation during neuronal development. Here, we report that c-Jun NH2-terminal kinase (JNK)-interacting protein-3 (JIP3) is highly expressed at axon tips during the critical period for axon development. Using gain- and loss-of-function approaches, immunofluorescence analysis, and in utero electroporation, we find that JIP3 can enhance axon elongation in primary hippocampal neurons and cortical neurons in vivo. We further demonstrate that JIP3 promotes axon elongation in a kinesin- and JNK-dependent manner using several deletion mutants of JIP3. Next, we demonstrate that the successful transportation of JIP3 to axon tips by kinesin is a prerequisite for enhancing JNK phosphorylation in this area and therefore promotes axon elongation, constituting a novel mechanism for coupling JIP3 anterograde transport with JNK signaling at the distal axons and axon elongation. Finally, our immunofluorescence data suggest that the activation of JNK at axon tips facilitates axon elongation by modulating cofilin activity and actin filament dynamics. These findings may have important implications for our understanding of neuronal axon elongation during development.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Axônios/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Cinesinas/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Neurônios/metabolismo , Actinas/metabolismo , Animais , Encéfalo/embriologia , Cofilina 1/metabolismo , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microfluídica , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
16.
Acta Biomater ; 177: 444-455, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38325709

RESUMO

Photodynamic therapy (PDT) is a clinically approved treatment for tumors, and it relies on the phototoxicity of photosensitizers by producing reactive oxygen species (ROS) to destroy cancer cells under light irradiation. However, such phototoxicity is a double-edged sword, which is also harmful to normal tissues. To manipulate phototoxicity and improve the therapy effect, herein we have proposed a dressing-undressing strategy for de-activating and re-activating therapy functions of photosensitizer nanoparticles. One kind of metal organic framework (PCN-224), which is composed of Zr(IV) cation and tetrakis (4-carboxyphenyl) porphyrin (TCPP), has been prepared as a model of photosensitizer, and it has size of ∼70 nm. These PCN-224 nanoparticles are subsequently coated with a mesoporous organic silica (MOS) shell containing tetrasulfide bonds (-S-S-S-S-), realizing the dressing of PCN-224. MOS shell has the thickness of ∼20 nm and thus can block 1O2 (diffusion distance: <10 nm), deactivating the phototoxicity and preventing the damage to skin and eyes. Furthermore, PCN-224@MOS can be used to load chemotherapy drug (DOX·HCl). When PCN-224@MOS-DOX are mixed with glutathione (GSH), MOS shell with -S-S-S-S- bonds can be reduced by GSH and then be decomposed, which results in the undressing and then confers the exposure of PCN-224 with good PDT function as well as the release of DOX. When PCN-224@MOS-DOX dispersion is injected into the mice and accumulated in the tumor, endogenous GSH also confers the undressing of PCN-224@MOS-DOX, realizing the in-situ activation of PDT and chemotherapy for tumor. Therefore, the present study not only demonstrates a general dressing-undressing strategy for manipulating phototoxicity of photosensitizers, but also provide some insights for precise therapy of tumors without side-effects. STATEMENT OF SIGNIFICANCE: Photosensitizers can generate reactive oxygen species (ROS) under light radiation to destroy cancer cells. However, this phototoxicity is a double-edged sword and also harmful to normal tissues such as the skin and eyes. To control phototoxicity and improve therapeutic efficacy, we prepared a PCN-224@MOS-DOX nanoplatform and proposed a dressing and undressing strategy to deactivate and reactivate the therapeutic function of the photosensitizer nanoparticles. The MOS shell can block the diffusion of 1O2, eliminate phototoxicity, and prevent damage to the skin and eyes. When injected into mice and accumulated in tumors, PCN-224@MOS-DOX dispersions are endowed with an endogenous GSH-driven undressing effect, achieving in situ activation of PDT and tumor chemotherapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Camundongos , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio , Neoplasias/tratamento farmacológico , Nanopartículas/uso terapêutico , Nanopartículas/química , Oxigênio , Dióxido de Silício/uso terapêutico , Bandagens , Linhagem Celular Tumoral
17.
J Colloid Interface Sci ; 659: 474-485, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38183813

RESUMO

Reactive chemical bonds are associated with the generation of therapeutic radicals and gases under internal-external stimuli, which are highly attractive for cancer treatments. However, designing multifunctional nanostructures that incorporate multiple chemical bonds remains a significant challenge. Herein, novel core-shell nanobombs integrating azo (NN) and tetrasulfide bonds (SSSS) have been constructed with sensitive ignition by both near-infrared (NIR) laser and tumor microenvironments (TME) for treating colorectal tumors. The nanobombs (GNR/AIPH@MON@PVP, GAMP) were prepared by the in-situ growth of tetrasulfide-contained mesoporous organosilica nanoshell (MON) on gold nanorods (GNR) as the photothermal initiator, the load of azo compound (AIPH) as the radical producer and polymer modification. Upon NIR irradiation, the GNR core exhibits stable and high photothermal effects because of the passivation of the MON shell, leading to the thermal ablation of cancer cells. Simultaneously, the local hyperthermia ignites AIPH to release alkyl radicals to cause extensive oxidative stress without oxygen dependence. Moreover, the MON shell can be gradually decomposed in a reduced environment and release therapeutic H2S gas because of the cleavage of SSSS bonds by the glutathione (GSH) overexpressed in TME, causing mitochondrial injury. Owing to multifunctional functions, the GAMP significantly inhibits the growth rate of tumors upon NIR irradiation and achieves the highest efficacy among treatments. Therefore, this study presents activatable nanoagents containing multiple chemical bonds and provides insights into developing comprehensive antitumor strategies.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Nanopartículas , Neoplasias , Humanos , Terapia Combinada , Neoplasias/tratamento farmacológico , Estresse Oxidativo , Neoplasias Colorretais/terapia , Linhagem Celular Tumoral , Nanopartículas/química , Microambiente Tumoral
18.
J Colloid Interface Sci ; 668: 88-97, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38669999

RESUMO

Nanotheranostic platforms, which can respond to tumor microenvironments (TME, such as low pH and hypoxia), are immensely appealing for photodynamic therapy (PDT). However, hypoxia in solid tumors harms the treatment outcome of PDT which depends on oxygen molecules to generate cytotoxic singlet oxygen (1O2). Herein, we report the design of TME-responsive smart nanotheranostic platform (DOX/ZnO2@Zr-Ce6/Pt/PEG) which can generate endogenously hydrogen peroxide (H2O2) and oxygen (O2) to alleviate hypoxia for improving photodynamic-chemo combination therapy of tumors. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite was prepared by the synthesis of ZnO2 nanoparticles, in-situ assembly of Zr-Ce6 as typical metal-organic framework (MOF) on ZnO2 surface, in-situ reduction of Pt nanozymes, amphiphilic lipids surface coating and then doxorubicin (DOX) loading. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite exhibits average sizes of ∼78 nm and possesses a good loading capacity (48.8 %) for DOX. When DOX/ZnO2@Zr-Ce6/Pt/PEG dispersions are intratumorally injected into mice, the weak acidic TEM induces the decomposition of ZnO2 core to generate endogenously H2O2, then Pt nanozymes catalyze H2O2 to produce O2 for alleviating tumor hypoxia. Upon laser (630 nm) irradiation, the Zr-Ce6 component in DOX/ZnO2@Zr-Ce6/Pt/PEG can produce cytotoxic 1O2, and 1O2 generation rate can be enhanced by 2.94 times due to the cascaded generation of endogenous H2O2/O2. Furthermore, the generated O2 can suppress the expression of hypoxia-inducible factor α, and further enable tumor cells to become more sensitive to chemotherapy, thereby leading to an increased effectiveness of chemotherapy treatment. The photodynamic-chemo combination therapy from DOX/ZnO2@Zr-Ce6/Pt/PEG nanoplatform exhibits remarkable tumor growth inhibition compared to chemotherapy or PDT. Thus, the present study is a good demonstration of a TME-responsive nanoplatform in a multimodal approach for cancer therapy.


Assuntos
Doxorrubicina , Peróxido de Hidrogênio , Oxigênio , Fotoquimioterapia , Nanomedicina Teranóstica , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Animais , Camundongos , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Oxigênio/química , Oxigênio/metabolismo , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Tamanho da Partícula , Propriedades de Superfície , Ensaios de Seleção de Medicamentos Antitumorais , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Peróxidos/química , Peróxidos/farmacologia , Nanopartículas/química , Camundongos Endogâmicos BALB C , Zinco/química , Zinco/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administração & dosagem
19.
Adv Healthc Mater ; : e2400127, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691349

RESUMO

Venous/arterial thrombosis poses significant threats to human health. However, drug-enabled thrombolysis treatment often encounters challenges such as short half-life and low bioavailability. To address these issues, the design of erythrocyte-membrane (EM) camouflaged nanocapsules (USIO/UK@EM) incorporating ultra-small iron oxide (USIO) and urokinase (UK) drug, which exhibits remarkable photothermal/magnetothermal effects and drug delivery ability for venous/arterial thrombolysis, is reported. USIO, UK, and EM are coextruded to fabricate USIO/UK@EM with average sizes of 103.7 nm. As USIO/UK@EM possesses wide photoabsorption and good magnetic properties, its solution demonstrates a temperature increase to 41.8-42.9 °C within 5 min when exposed to an 808 nm laser (0.33 mW cm-2) or alternating magnetic field (AMF). Such photothermal/magnetothermal effect along with UK confers impressive thrombolytic rates of 82.4% and 74.2%, higher than that (≈15%) achieved by UK alone. Further, the EM coating extends the circulating half-life (t1/2 = 3.28 h). When USIO/UK@EM is administered to mice and rabbits, tail vein thrombus in mice and femoral artery thrombus in rabbits can be dissolved by the synergetic effect of thermothrombolysis and UK. Therefore, this study not only offers insights into the rational design of multifunctional biomimetic nanocapsules but also showcases a promising thrombolysis strategy utilizing nanomedicine.

20.
Adv Healthc Mater ; 13(15): e2400049, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38416676

RESUMO

Wound healing and infection remain significant challenges due to the ineffectiveness against multidrug-resistant (MDR) bacteria and the complex oxidative wound microenvironments. To address these issues, thymoquinone-reinforced injectable and thermosensitive TQ@PEG-PAF-Cur hydrogels with dual functions of microenvironment reshaping and photodynamic therapy are developed. The hydrogel comprises natural compound thymoquinone (TQ) and poly (ethylene glycol)-block-poly (alanine-co-phenyl alanine) copolymers (PEG-PAF) conjugated with natural photosensitizer curcumin (Cur). The incorporation of TQ and Cur reduces the sol-to-gel transition temperature of TQ@PEG-PAF-Cur to 30°C, compared to PEG-PAF hydrogel (37°C), due to the formation of strong hydrogen bonding, matching the wound microenvironment temperature. Under blue light excitation, TQ@PEG-PAF-Cur generates significant amounts of reactive oxygen species such as H2O2, 1O2, and ·OH, exhibiting rapid and efficient bactericidal capacities against methicillin-resistant Staphylococcus aureus and broad spectrum ß-lactamases Escherichia coli via photodynamic therapy (PDT). Additionally, Cur effectively inhibits the expressions of proinflammatory cytokines in skin tissue-forming cells. As a result, the composite hydrogel can rapidly transform into a gel to cover the wound, reshape the wound microenvironment, and accelerate wound healing in vivo. This collaborative antibacterial strategy provides valuable insights to guide the development of multifunctional materials for efficient wound healing.


Assuntos
Curcumina , Farmacorresistência Bacteriana Múltipla , Hidrogéis , Staphylococcus aureus Resistente à Meticilina , Cicatrização , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Curcumina/farmacologia , Curcumina/química , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Fotoquimioterapia/métodos , Antibacterianos/farmacologia , Antibacterianos/química , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Camundongos , Escherichia coli/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Fototerapia/métodos , Humanos
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