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1.
Mol Ther ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34628054

RESUMO

Plasma levels of neuropeptide Y (NPY) are elevated in patients with acute myocardial infarction (AMI), but its role in AMI remains unclear, which was examined here in NPY WT/KO mice treated with/without exogenous NPY and its Y1 receptor antagonist (Y1Ra) BIBP 3226. We found that AMI mice lacking NPY developed more severe AMI than WT mice with worse cardiac dysfunction, progressive cardiac inflammation and fibrosis, excessive apoptosis, but impairing angiogenesis. All these changes were reversed by a rescued study with exogenous NPY dose-dependently. Interestingly, treatment with NPY also dose-dependently attenuated AMI in WT mice, which was blocked by BIBP 3226. Phenotypically, cardiac NPY was de novo expressed by infiltrating macrophages during the repairing or fibrosing process in heart failure patients and AMI mice. Mechanistically, NPY was induced by TGF-ß1 in bone marrow-derived macrophages and signaled through its Y1R to exert its pathophysiological activities by inhibiting p38/NF-κB-mediated M1 macrophage activation while promoting the reparative M2 phenotype in vivo and in vitro, In conclusions, NPY can attenuate AMI in mice. Inhibition of cardiac inflammation and fibrosis while enhancing angiogenesis but reducing apoptosis may be the underlying mechanisms through which NPY attenuates cardiac remodeling and deterioration of function following AMI.

2.
J Nanobiotechnology ; 19(1): 312, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635104

RESUMO

The inherent heterogeneity of individual cells in cell populations plays significant roles in disease development and progression, which is critical for disease diagnosis and treatment. Substantial evidences show that the majority of traditional gene profiling methods mask the difference of individual cells. Single cell sequencing can provide data to characterize the inherent heterogeneity of individual cells, and reveal complex and rare cell populations. Different microfluidic technologies have emerged for single cell researches and become the frontiers and hot topics over the past decade. In this review article, we introduce the processes of single cell sequencing, and review the principles of microfluidics for single cell analysis. Also, we discuss the common high-throughput single cell sequencing technologies along with their advantages and disadvantages. Lastly, microfluidics applications in single cell sequencing technology for the diagnosis of cancers and immune system diseases are briefly illustrated.

3.
Int J Nanomedicine ; 16: 6003-6016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511902

RESUMO

Introduction: Traditional antitumor chemotherapy faces great challenges, such as multi-drug resistance (MDR) and poor penetration into tumor tissues. The newly emerging nitric oxide (NO)-based gas therapy has been recognized to reduce MDR and has improved permeation into tumor tissue. Methods: In this study, NO-generating prodrug sodium nitroprusside (SNP) was doped to hollow mesoporous Prussian blue (PB) nanoparticles to fabricate NO-generating nanoparticles (NO-PB), which was further loaded with doxorubicin (DOX). Results: DOX loaded NO-PB (DOX-NO-PB) was released quicker at pH 6 compared with neutral pH, suggesting NO-PB may facilitate the release of loaded drug in acidic tumor tissue. The capacity of NO production by NO-PB was measured, and the results showed the presence of NO in the culture medium from 4T1 cells incubated with NO-PB and inside the cells. NP-PB could be detected by photoacoustic imaging (PAI) in tumor tissue in 4T1 tumor bearing mice, suggesting this nanoparticle may serve as contrast agent for the noninvasive diagnosis of tumor tissues. NO-PB suppressed the growth of tissues in 4T1 tumor bearing mice. DOX-NO-PB showed more potent anti-tumor effects in 4T1 cells and tumor bearing mice compared with free DOX and NO-PB alone, indicating that the combination of DOX and NO-PB exhibited synergistic effects on tumor suppression. Conclusion: This study provides a novel nanocarrier for gas therapy with additional PAI imaging capacity. This nanocarrier can be utilized for combination therapy of NO and chemotherapeutics which may serve as theranostic agents.

4.
Small ; 17(40): e2102470, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34480417

RESUMO

Tumor cells adapt to excessive oxidative stress by actuating reactive oxygen species (ROS)-defensing system, leading to a resistance to oxidation therapy. In this work, self-delivery photodynamic synergists (designated as PhotoSyn) are developed for oxidative damage amplified tumor therapy. Specifically, PhotoSyn are fabricated by the self-assembly of chlorine e6 (Ce6) and TH588 through π-π stacking and hydrophobic interactions. Without additional carriers, nanoscale PhotoSyn possess an extremely high drug loading rate (up to 100%) and they are found to be fairly stable in aqueous phase with a uniform size distribution. Intravenously injected PhotoSyn prefer to accumulate at tumor sites for effective cellular uptake. More importantly, TH588-mediated MTH1 inhibition could destroy the ROS-defensing system of tumor cells by preventing the elimination of 8-oxo-2'-deoxyguanosine triphosphate (8-oxo-dG), thereby exacerbating the oxidative DNA damage induced by the photodynamic therapy (PDT) of Ce6 under light irradiation. As a consequence, PhotoSyn exhibit enhanced photo toxicity and a significant antitumor effect. This amplified oxidative damage strategy improves the PDT efficiency with a reduced side effect by increasing the lethality of ROS without generating superabundant ROS, which would provide a new insight for developing self-delivery nanoplatforms in photodynamic tumor therapy in clinic.

5.
Signal Transduct Target Ther ; 6(1): 247, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34210954

RESUMO

Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals. Inflammasome multiprotein complexes are composed of three parts: a sensor protein, an adaptor, and pro-caspase-1. Activation of the inflammasome leads to the activation of caspase-1, which cleaves pro-inflammatory cytokines such as IL-1ß and IL-18, leading to pyroptosis. Effectors of the inflammasome not only provide protection against infectious pathogens, but also mediate control over sterile insults. Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases, cancer, and neurodegenerative disorders. Here, we review the role of the inflammasome as a double-edged sword in various diseases, and the outcomes can be either good or bad depending on the disease, as well as the genetic background. We highlight inflammasome memory and the two-shot activation process. We also propose the M- and N-type inflammation model, and discuss how the inflammasome pathway may be targeted for the development of novel therapy.

6.
Int J Nanomedicine ; 16: 4197-4208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34188469

RESUMO

Introduction: Intracellular protein delivery is emerging as a potential strategy to revolutionize therapeutics in the field of biomedicine, aiming at treating a wide range of diseases including cancer, inflammatory diseases and other oxidative stress-related disorders with high specificity. However, the current challenges and limitations are addressed to either synthetically or biologically through multipotency of engineering, such as protein modification, insufficient delivery of large-size proteins, deficiency or mutation of proteins, and high cytotoxicity. Methods: We prepared the nanocomposites by mixing protein with PEI1200 at a certain molar ratio and demonstrated that it can deliver proteins into living cells in high efficiency and safety through the following experiments, such as dynamic light scattering, fluorescent detection, agarose gel electrophoresis, ß-Galactosidase activity detection, immunofluorescence staining, digital fluorescent detection, cell viability assay and flow cytometry. Results: The self-assembly of PEI1200/protein nanocomposites with appropriate molar ratio (4:1 and 8:1) could provide efficiently delivery of active proteins to a variety of cell types in the presence of serum. The nanocomposites could continuously release protein up to 96 h in their desired intracellular locations. In addition, these nanocomposites were able to preserve protein activity while maintain low cytotoxicity (when final concentration <1 µg/mL). Conclusion: Collectively, PEI1200-based delivery system provided an alternative strategy to direct protein delivery in high efficiency and safety, offering increased potential applications in clinical biomedicine.


Assuntos
Espaço Intracelular/metabolismo , Polietilenoimina/química , Proteínas/administração & dosagem , Morte Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Proteínas de Fluorescência Verde/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Peso Molecular , Nanocompostos/química , Nanocompostos/ultraestrutura
7.
Adv Healthc Mater ; 10(12): e2100198, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33938637

RESUMO

Photodynamic therapy (PDT) often suffers from the exacerbated tumor hypoxia and the heterogeneous distribution of photosensitizers, leading to an inefficient ROS productivity and availability. In this work, a mitochondria targeted O2 economizer (designated as Mito-OxE) is developed to improve PDT efficiency by alleviating tumor hypoxia and enhancing the subcellular localization of photosensitizers. Specifically, the photosensitizer of protoporphyrin IX (PpIX) is modified with the hydrophilic polyethylene glycol and the lipophilic cation of triphenylphosphine (TPP) to fabricate the biocompatible mitochondria targeted photosensitizers (designated as Mito-PSs). And Mito-OxE is prepared by using Mito-PSs to load the mitochondrial oxidative phosphorylation inhibitors of atovaquone (ATO). Benefiting from the targeting capability of TPP, Mito-OxE can selectively accumulate in mitochondria after cellular uptake. Subsequently, the mitochondrial respiration would be suppressed to with the participation of ATO, resulting in a local hypoxia mitigation for enhanced PDT. Compared with Mito-PSs, Mito-OxE maximizes the therapeutic effect against hypoxic tumors under light irradiation. This design of mitochondria targeted O2 economizer would advance the development of targeted drug delivery system for effective PDT regardless of hypoxic microenvironment.


Assuntos
Nanopartículas , Fotoquimioterapia , Linhagem Celular Tumoral , Humanos , Hipóxia/metabolismo , Mitocôndrias/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Hipóxia Tumoral
8.
Biomater Sci ; 9(9): 3445-3452, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33949456

RESUMO

Multidrug resistance (MDR) is one of the prime reasons for the failure of cancer chemotherapy, which continues to be a great challenge to be solved. In this work, α-tocopherol succinate (α-TOS) and doxorubicin (DOX)-based self-delivery nanomedicine (designated as α-TD) is prepared to combat drug resistance for cancer synergistic chemotherapy. Carrier-free α-TD possesses a fairly high drug loading rate and improves the cellular uptake via the endocytosis pathway. More importantly, the apoptotic inducer α-TOS could elevate the reactive oxygen species (ROS) generation, disrupt mitochondrial function and reduce adenosine 5'-triphosphate (ATP) production, which facilitate the intracellular drug retention while decreasing its efflux. As a result, α-TD achieves a considerable synergistic chemotherapeutic effect against drug resistant cancer cells. Moreover, it also exhibits a preferable inhibitory effect on tumor growth with a low system toxicity in vivo. This synergistic drug self-delivery strategy would open a new window for developing carrier-free nanomedicine for overcoming drug resistance in cancer therapy.


Assuntos
Antineoplásicos , Nanopartículas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Portadores de Fármacos/farmacologia , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Células MCF-7 , Nanomedicina
9.
Acta Pharmacol Sin ; 42(9): 1486-1497, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33893396

RESUMO

Non-small cell lung cancer (NSCLC) is characterized by a high incidence of metastasis and poor survival. As epithelial-mesenchymal transition (EMT) is well recognized as a major factor initiating tumor metastasis, developing EMT inhibitor could be a feasible treatment for metastatic NSCLC. Recent studies show that triptolide isolated from Tripterygium wilfordii Hook F attenuated the migration and invasion of breast cancer, colon carcinoma, and ovarian cancer cells, and EMT played important roles in this process. In the present study we investigated the effect of triptolide on the migration and invasion of NSCLC cell lines. We showed that triptolide (0.5, 1.0, 2.0 nM) concentration-dependently inhibited the migration and invasion of NCI-H1299 cells. Triptolide treatment concentration-dependently suppressed EMT in NCI-H1299 cells, evidenced by significantly elevated E-cadherin expression and reduced expression of ZEB1, vimentin, and slug. Furthermore, triptolide treatment suppressed ß-catenin expression in NCI-H1299 and NCI-H460 cells, overexpression of ß-catenin antagonized triptolide-caused inhibition on EMT, whereas knockout of ß-catenin enhanced the inhibitory effect of triptolide on EMT. Administration of triptolide (0.75, 1.5 mg/kg per day, ip, every 2 days) for 18 days in NCI-H1299 xenograft mice dose-dependently suppressed the tumor growth, restrained EMT, and decreased lung metastasis, as evidence by significantly decreased expression of mesenchymal markers, increased expression of epithelial markers as well as reduced number of pulmonary lung metastatic foci. These results demonstrate that triptolide suppresses NSCLC metastasis by targeting EMT via reducing ß-catenin expression. Our study implies that triptolide may be developed as a potential agent for the therapy of NSCLC metastasis.

10.
J Colloid Interface Sci ; 593: 323-334, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33744541

RESUMO

In recent years, chemodynamic therapy (CDT) has gained increasing interest in cancer treatment. In contrast to photodynamic therapy and sonodynamic therapy, extrinsic excitations such as laser or ultrasound are not required in CDT. As a result, the CDT performance is not limited by the penetration depth of the external irritation. However, CDT relies heavily on hydrogen peroxide (H2O2) in the tumour microenvironment (TME). Insufficient H2O2 in the TME limits the CDT performance, and the most reported methods to produce H2O2 in the TME are dependent on oxygen supply, which is restricted by the hypoxic TME. In this study, H2O2 self-providing copper nanodots were proposed, and the drug doxorubicin (DOX) was successfully loaded to construct DOX-nanodots. Our results showed that the nanodots produced H2O2 in the weakly acidic TME due to the peroxo group and further generated the most active hydroxyl radical (OH) through the Fenton-like reaction. This process was pH-dependent and did not occur in a neutral environment. In addition to OH, the nanodots also produced singlet oxygen (1O2) and superoxide anions (O2-) in the cancer cells. The copper nanodots performed promising CDT against breast cancer in vitro and in vivo, with enhanced cell apoptosis and decreased cell proliferation. The combination of chemotherapy and CDT using DOX-nanodots further improved the therapeutic effects. The treatments showed good biocompatibility with no obvious toxicity in major tissues, possibly due to the specific OH generation in the weakly acidic TME. In summary, the H2O2 self-providing copper nanodots in combination with DOX showed promising cancer-curing effects due to the oxygen-independent and tumour-specific production of reactive oxygen species and the cooperation of chemotherapy.


Assuntos
Neoplasias da Mama , Peróxido de Hidrogênio , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Cobre , Doxorrubicina/farmacologia , Feminino , Humanos , Microambiente Tumoral
12.
J Pharm Biomed Anal ; 197: 113969, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33636646

RESUMO

Previous studies have reported that nucleic acid methylation is a critical element in cardiovascular disease, and most studies mainly focused on sequencing and biochemical research. Here we developed an Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) method for the quantification analysis of the dissociative epigenetic modified nucleosides (5mdC, 5mrC, m6A) in Myocardial Infarction (MI) SD rats from different periods (1 week, 4 weeks, 8 weeks) after the surgery. The samples for analysis were obtained from heart tissue and blood of the rats. All the quantification results are compared with the sham-operated group. Total RNA and DNA were isolated by enzymatic hydrolytic methods before the UPLC-MS/MS analysis. The statistical analysis demonstrates the dynamic changes of modified nucleosides in MI rats, and it showed good specificity, accuracy, stability and less samples were needed in the method. In this paper, we discovered that the concentration of 5mdC, 5mrC, m6A from heart tissue significantly increased at 8 weeks after the surgery. Furthermore, UPLC-MS/MS helps us observe the similar change of the concentration of those 3 methylated biomarkers in peripheral blood after 8 weeks. The result shows that the dynamic process of those 3 methylated biomarkers in peripheral blood is related to the content of methylated biomarkers from the heart tissue. Based on the scientific evidence available, we proved that the methylation of genetic materials in peripheral blood is similar to myocardial infarction tissue. The relation between them indicates that peripheral blood could be a promising alternative to the heart tissue which monitor the level of methylation and MI diagnosis-aided.


Assuntos
RNA , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Metilação de DNA , Ratos , Ratos Sprague-Dawley
13.
Acta Pharmacol Sin ; 42(10): 1587-1597, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33495518

RESUMO

Antiepileptic drug zonisamide has been shown to be curative for Parkinson's disease (PD) through increasing HMG-CoA reductase degradation protein 1 (Hrd1) level and mitigating endoplasmic reticulum (ER) stress. Hrd1 is an ER-transmembrane E3 ubiquitin ligase, which is involved in cardiac dysfunction and cardiac hypertrophy in a mouse model of pressure overload. In this study, we investigated whether zonisamide alleviated cardiac hypertrophy in rats by increasing Hrd1 expression and inhibiting ER stress. The beneficial effects of zonisamide were assessed in two experimental models of cardiac hypertrophy: in rats subjected to abdominal aorta constriction (AAC) and treated with zonisamide (14, 28, 56 mg · kg-1 · d-1, i.g.) for 6 weeks as well as in neonatal rat cardiomyocytes (NRCMs) co-treated with Ang II (10 µM) and zonisamide (0.3 µM). Echocardiography analysis revealed that zonsiamide treatment significantly improved cardiac function in AAC rats. We found that zonsiamide treatment significantly attenuated cardiac hypertrophy and fibrosis, and suppressed apoptosis and ER stress in the hearts of AAC rats and in Ang II-treated NRCMs. Importantly, zonisamide markedly increased the expression of Hrd1 in the hearts of AAC rats and in Ang II-treated NRCMs. Furthermore, we demonstrated that zonisamide accelerated ER-associated protein degradation (ERAD) in Ang II-treated NRCMs; knockdown of Hrd1 abrogated the inhibitory effects of zonisamide on ER stress and cardiac hypertrophy. Taken together, our results demonstrate that zonisamide is effective in preserving heart structure and function in the experimental models of pathological cardiac hypertrophy. Zonisamide increases Hrd1 expression, thus preventing cardiac hypertrophy and improving the cardiac function of AAC rats.

14.
Nanotheranostics ; 5(1): 73-89, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391976

RESUMO

Microfluidic chip is not a chip in the traditional sense. It is technologies that control fluids at the micro level. As a burgeoning biochip, microfluidic chips integrate multiple disciplines, including physiology, pathology, cell biology, biophysics, engineering mechanics, mechanical design, materials science, and so on. The application of microfluidic chip has shown tremendous promise in the field of cancer therapy in the past three decades. Various types of cell and tissue cultures, including 2D cell culture, 3D cell culture and tissue organoid culture could be performed on microfluidic chips. Patient-derived cancer cells and tissues can be cultured on microfluidic chips in a visible, controllable, and high-throughput manner, which greatly advances the process of personalized medicine. Moreover, the functionality of microfluidic chip is greatly expanding due to the customizable nature. In this review, we introduce its application in developing cancer preclinical models, detecting cancer biomarkers, screening anti-cancer drugs, exploring tumor heterogeneity and producing nano-drugs. We highlight the functions and recent development of microfluidic chip to provide references for advancing cancer diagnosis and treatment.


Assuntos
Técnicas Analíticas Microfluídicas/instrumentação , Neoplasias/diagnóstico , Antineoplásicos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico
15.
Med Res Rev ; 41(1): 314-341, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32969064

RESUMO

The global incidence of cardiac diseases is expected to increase in the coming years, imposing a substantial socioeconomic burden on healthcare systems. Autophagy is a tightly regulated lysosomal degradation mechanism important for cell survival, homeostasis, and function. Accumulating pieces of evidence have indicated a major role of autophagy in the regulation of cardiac homeostasis and function. It is well established that dysregulation of autophagy in cardiomyocytes is involved in cardiac hypertrophy, myocardial infarction, diabetic cardiomyopathy, and heart failure. In this sense, autophagy seems to be an attractive therapeutic target for cardiac diseases. Recently, multiple natural products/phytochemicals, such as resveratrol, berberine, and curcumin have been shown to regulate cardiomyocyte autophagy via different pathways. The autophagy-modifying capacity of these compounds should be taken into consideration for designing novel therapeutic agents. This review focuses on the role of autophagy in various cardiac diseases and the pharmacological basis and therapeutic potential of reported natural products in cardiac diseases by modifying autophagic processes.

16.
Comput Struct Biotechnol J ; 18: 2920-2930, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33163152

RESUMO

The distribution and dynamics of biomolecules in the cell is of critical interest in biological research. Raman imaging techniques have expanded our knowledge of cellular biological systems significantly. The technological developments that have led to the optimization of Raman instrumentation have helped to improve the speed of the measurement and the sensitivity. As well as instrumental developments, data mining plays a significant role in revealing the complicated chemical information contained within the spectral data. A number of data mining methods have been applied to extract the spectral information and translate them into biological information. Single-cell visualization, cell classification and biomolecular/drug quantification have all been achieved by the application of data mining to Raman imaging data. Herein we summarize the framework for Raman imaging data analysis, which involves preprocessing, pattern recognition and validation. There are multiple methods developed for each stage of analysis. The characteristics of these methods are described in relation to their application in Raman imaging of the cell. Furthermore, we summarize the software that can facilitate the implementation of these methods. Through its careful selection and application, data mining can act as an essential tool in the exploration of information-rich Raman spectral data.

17.
ACS Nano ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33236625

RESUMO

Self-delivery of photosensitizer and immune modulator to tumor site is highly recommendable to improve the photodynamic immunotherapy yet remains challenging. Herein, self-delivery photoimmune stimulators (designated as iPSs) are developed for photodynamic sensitized tumor immunotherapy. Carrier-free iPSs are constructed by optimizing the noncovalent interactions between the pure drugs of chlorine e6 (Ce6) and NLG919, which avoid the excipients-raised toxicity and immunogenicity. Intravenously administrated iPSs prefer to passively accumulate on tumor tissues for a robust photodynamic therapy (PDT) with the induction of immunogenetic cell death (ICD) cascade to activate cytotoxic T lymphocytes (CTLs) and initiate antitumor immune response. Meanwhile, the concomitant delivery of NLG919 inhibits the activation of indoleamine 2,3-dioxygenase 1 (IDO-1) to reverse the immunosuppressive tumor microenvironment. Ultimately, the photodynamic sensitized immunotherapy with iPSs efficiently inhibit the primary and distant tumor growth with a low system toxicity, which would shed light on the development of self-delivery nanomedicine for clinical transformation in tumor precision therapy.

18.
Acta Biomater ; 117: 349-360, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33010514

RESUMO

Development of antitumor agents with high efficiency and low toxicity is one of the most important goals for biomedical research. However, most traditional therapeutic strategies were limited due to their non-specificity and abnormal tumor microenvironments, causing a poor therapeutic efficiency and severe side effects. In this paper, a tumor targeted self-synergistic nanoplatform (designated as PAO@PCN@HA) was developed for chemotherapy sensitized photodynamic therapy (PDT) against hypoxic tumors. The efficient drug loading of phenylarsine oxide (PAO) in porphyrinic metal organic framework of PCN-224 as well as the surface modification of hyaluronic acid (HA) improved the targeted drug delivery and reduced the side effects of PAO at the therapeutic dose. Particularly, PAO as an arsenical-based chemotherapeutic agent could not only induce cell apoptosis by generating reactive oxygen species (ROS), but also regulate tumor microenvironments to improve the PDT effect of PCN-224 by mitigating hypoxia and consuming cellular GSH. Both in vitro and in vivo investigations confirmed an effective self-synergy of PAO@PCN@HA in hypoxic tumor therapy with a low systemic toxicity. This integration of microenvironment adjustment with tumor targeted self-synergistic mechanism might provide a new insight for the development of arsenic-based antitumor strategy for clinical applications.


Assuntos
Antineoplásicos , Arsênio , Neoplasias , Fotoquimioterapia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Arsênio/uso terapêutico , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Microambiente Tumoral
19.
J Nanobiotechnology ; 18(1): 146, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076924

RESUMO

BACKGROUNDS: Surgical resection and adjunct chemotherapy or radio-therapy has been applied for the therapy of superficial malignant tumor in clinics. Whereas, there are still some problems limit its clinical use, such as severe pains and side effect. Thus, it is urgent need to develop effective, minimally invasive and low toxicity therapy stagey for superficial malignant tumor. Topical drug administration such as microneedle patches shows the advantages of reduced systemic toxicity and nimble application and, as a result, a great potential to treat superficial tumors. METHODS: In this study, microneedle (MN) patches were fabricated to deliver photosensitizer IR820 and chemotherapy agent cisplatin (CDDP) for synergistic chemo-photodynamic therapy against breast cancer. RESULTS: The MN could be completely inserted into the skin and the compounds carrying tips could be embedded within the target issue for locoregional cancer treatment. The photodynamic therapeutic effects can be precisely controlled and switched on and off on demand simply by adjusting laser. The used base material vinylpyrrolidone-vinyl acetate copolymer (PVPVA) is soluble in both ethanol and water, facilitating the load of both water-soluble and water-insoluble drugs. CONCLUSIONS: Thus, the developed MN patch offers an effective, user-friendly, controllable and low-toxicity option for patients requiring long-term and repeated cancer treatments.

20.
J Nanobiotechnology ; 18(1): 110, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762751

RESUMO

BACKGROUNDS: Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time-consuming. METHODS: In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent. RESULTS: The preparation method is easy and cost-effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first-order elimination kinetics and, it has a short half-life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility. CONCLUSIONS: This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.


Assuntos
Bismuto , Meios de Contraste , Tomografia Computadorizada por Raios X/métodos , Animais , Bismuto/química , Bismuto/farmacocinética , Bismuto/toxicidade , Meios de Contraste/química , Meios de Contraste/farmacocinética , Meios de Contraste/toxicidade , Iohexol/química , Iohexol/farmacocinética , Rim/diagnóstico por imagem , Rim/metabolismo , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Camundongos , Ácido Pentético/química , Ácido Pentético/farmacocinética , Distribuição Tecidual , Imagem Corporal Total
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