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Pancreatic cancer is one of the most lethal tumors due to its rapid proliferation and aggressiveness. RAD51AP1 is a protein-coding gene with critical functions in many cancers but few studies have assessed RAD51AP1 in pancreatic cancer. Bioinformatics methods and cell function experiments were performed to reveal the functions of RAD51AP1 in vitro. Gene Expression Profiling Interactive Analysis (GEPIA) was used to explore key proteins and their relationships with RAD51AP1 in the PI3K/AKT/NF-κB signaling pathways. Western blotting (WB) was conducted to detect the expression of key proteins after the downregulation of RAD51AP1. Co-Immunoprecipitation (Co-IP) was applied to confirm the binding of RAD51AP1 and PI3K. In addition, the lentivirus was used to construct subcutaneous tumors in nude mice to verify the function of RAD51AP1 in vivo. The Kaplan-Meier curves illustrated that elevated expression levels of RAD51AP1 were significantly correlated with reduced overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in pancreatic cancer patients. The results of WB showed that several key proteins in the PI3K/AKT/NF-κB signaling pathway (including PI3K, AKT, IKK1, IKK2, P65, P50, C-FLIP, and XIAP) exhibited a significant knockdown upon reducing the expression of RAD51AP1. Co-IP suggested that RAD51AP1 could directly bind to PI3K. In vitro, CCK-8, wound healing, and Transwell assays revealed that high RAD51AP1 expression was significantly correlated with increased cell proliferation, migration, and invasion. In vivo, mouse tumor formation experiments showed that RAD51AP1 inhibition significantly inhibited tumor growth. RAD51AP1 plays an important role in fostering cellular proliferation, invasion, metastasis, and tumor enlargement via the PI3K/AKT/NF-κB signaling pathway.
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NF-kappa B , Neoplasias Pancreáticas , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Camundongos Nus , NF-kappa B/metabolismo , Neoplasias Pancreáticas/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais/fisiologiaRESUMO
Psychological stress may be linked to cancer incidence; however, more direct evidence is required to support this viewpoint. In this study, we investigated the effects of stress on immunosurveillance against cancer cells using a previously established examination stress model. We showed that the cancer killing activity (CKA) of granulocytes (also known as polymorphic nuclear cells, PMNs) is sharply reduced during examination stress stimulation in some donors who are psychologically sensitive to examination stress, with the concentration of plasma stress hormones (cortisone, epinephrine, and norepinephrine) increasing accordingly. The effects of stress hormones on immune cell CKA were also investigated under two in vitro co-incubation conditions, with all three hormones found to exert inhibitory effects on the CKA of PMNs and mononuclear cells. We showed that stress triggered the release of stress hormones which had profound inhibitory effects on the innate anticancer functions of PMNs. These results provide a possible explanation for the relationship between psychological stress and cancer incidence.
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Granulócitos/fisiologia , Neoplasias/fisiopatologia , Estresse Psicológico/complicações , Estresse Psicológico/fisiopatologia , Epinefrina/sangue , Epinefrina/fisiologia , Humanos , Hidrocortisona/sangue , Hidrocortisona/fisiologia , Norepinefrina/sangue , Norepinefrina/fisiologiaRESUMO
Myocardial infarction (MI) results in an impaired heart function. Conductive hydrogel patch-based therapy has been considered as a promising strategy for cardiac repair after MI. In our study, we fabricated a three-dimensional (3D) printed conductive hydrogel patch made of fibrinogen scaffolds and mesenchymal stem cells (MSCs) combined with graphene oxide (GO) flakes (MSC@GO), capitalizing on GO's excellent mechanical property and electrical conductivity. The MSC@GO hydrogel patch can be attached to the epicardium via adhesion to provide strong electrical integration with infarcted hearts, as well as mechanical and regeneration support for the infarcted area, thereby up-regulating the expression of connexin 43 (Cx43) and resulting in effective MI repair in vivo. In addition, MI also triggers apoptosis and damage of cardiomyocytes (CMs), hindering the normal repair of the infarcted heart. GO flakes exhibit a protective effect against the apoptosis of implanted MSCs. In the mouse model of MI, MSC@GO hydrogel patch implantation supported cardiac repair by reducing cell apoptosis, promoting gap connexin protein Cx43 expression, and then boosting cardiac function. Together, this study demonstrated that the conductive hydrogel patch has versatile conductivity and mechanical support function and could therefore be a promising candidate for heart repair.
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Grafite , Hidrogéis , Infarto do Miocárdio , Ratos , Camundongos , Animais , Hidrogéis/farmacologia , Conexina 43 , Ratos Sprague-Dawley , Infarto do Miocárdio/cirurgia , Condutividade Elétrica , Impressão TridimensionalRESUMO
Metal-organic frameworks (MOFs) hold great promise for widespread applications in biomedicine and nanomedicine. MOFs are one of the most fascinating nanocarriers for drug delivery, benefiting from their high porosity and facile modification. Furthermore, the tailored components of MOFs can be therapeutic agents for various treatments, including drugs as organic ligands of MOFs, active metal as central metal ions of MOFs, and their combinations as carrier-free MOF-based nanodrug. In this review, the advances in delivery systems and applications as therapeutic agents for nanoscale MOF-based materials are summarized. The challenges of MOFs in clinical translation and the future directions in the field of MOFs therapy are also discussed. We hope that more researchers will focus their attention on advancing and translating MOF-based nanodrugs into pre-clinical and clinical applications.
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Estruturas Metalorgânicas , Nanomedicina , Sistemas de Liberação de Medicamentos , Metais , PorosidadeRESUMO
The electrical characteristic of cancer cells is neglected among tumor biomarkers. The development of nanoprobes with opposing charges for monitoring the unique electrophysiological characteristics of cancer cells. Micro-nano size adsorption binding necessitates consideration of the nanoprobe's specific surface area. On the basis of the electrophysiological characteristics of circulating tumor cells (CTCs), clinical application and performance assessment are determined. To demonstrate that cancer cells have a unique pattern of electrophysiological patterns compared to normal cells, fluorescent nanoprobes with opposing charges were developed and fabricated. Graphene oxide (GO) was used to transform three-dimensional (3D) nanoprobes into two-dimensional (2D) nanoprobes. Compare 2D and 3D electrophysiological magnetic nanoprobes (MNP) in clinical samples and evaluate the adaptability and development of CTCs detection based on cell electrophysiology. Positively charged nanoprobes rapidly bind to negatively charged cancer cells based on electrostatic interactions. Compared to MNPs(+) without GO, the GO/MNPs(+) nanoprobe is more efficient and uses less material to trap cancer cells. CTCs can be distinguished from normal cells that are fully unaffected by nanoprobes by microscopic cytomorphological inspection, enabling the tracking of the number and pathological abnormalities of CTCs in the same patient at various chemotherapy phases to determine the efficacy of treatment. The platform for recognizing CTCs on the basis of electrophysiological characteristics compensates for the absence of epithelial biomarker capture and size difference capture in clinical performance. Under the influence of electrostatic attraction, the binding surface area continues to influence the targeting of cancer cells by nanoprobes. The specific recognition and detection of nanoprobes based on cell electrophysiological patterns has enormous potential in the clinical diagnosis and therapeutic monitoring of cancer.
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Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Biomarcadores TumoraisRESUMO
PURPOSE: Cancer vaccine (CV) has thrived as a promising tool for cancer prevention and treatment. However, how to maintain the integrity and diversity of individualized vaccine antigens and activate the adaptive immune system is still challenging. METHODS: Herein, a preventive and therapeutic vaccine platform for in situ effective multi-model synergistic therapy is developed. In our study, we process B16F10 cells by liquid nitrogen frozen (LNF) to obtain LNF cells, the characterization of LNF cells were conducted. Moreover, the anti-tumor effect and immune activation ability were studied, and the role as a CV were investigated. RESULTS: The LNF cells preserve intact cellular structure and tumor-associated self-antigen gp100. Moreover, LNF cells have the ability of loading and releasing doxorubicin (DOX). Except for the anti-tumor effect of chemotherapy brought by DOX, the LNF cells can promote the maturation of dendritic cells (DCs) and induce immune response by activating CD4+ and CD8+ T cells, particularly with the existence of adjuvant, R848. Specifically, the CD8+ T cells of mice in LNF-DOX/R848 group are 6 times of that in PBS group in tumor microenvironment, and twice in spleen. Therefore, LNF cells can also be utilized as a CV. Vaccination with LNF/R848 cells effectively suppress the tumor growth in mice by fivefold as compared to the control group. CONCLUSION: In this work, we obtain the LNF cells with a simple procedure. The LNF cells not only provides a tumor cells-based multi-modal system for cancer therapy but inspires new insights into future development of individualized CVs strategies. This study processes live B16F10 cells by liquid nitrogen frozen to obtain LNF cells, which preserve cell integrity and homologous targeting ability. The LNF cells can load and deliver drug and can serve as tumor vaccine. Results demonstrated the LNF cells have effective prophylactic ability, and ideal anti-tumor ability with the loaded drug and adjuvant.
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Neutrophils, the most abundant white blood cells in the human body, are important immune cells responsible for the innate immune response. Neutrophils can migrate to inflammatory areas, such as tumor sites and infection sites, because of chemotaxis. Neutrophil-based nanomaterials, such as neutrophil-nanomaterial composites and neutrophil membrane-based nanomaterials, can help the drug or imaging agent gather in the inflammatory area with the help of chemotaxis. In addition, some nanomaterials can interfere with the function of neutrophils to treat tissue damage caused by excessive local accumulation of neutrophils. This review focuses on the interaction between nanomaterials and neutrophils as well as the applications of neutrophil-based nanomaterials and neutrophil-interfering nanomaterials.
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Nanopartículas , Neutrófilos , Humanos , Nanopartículas/uso terapêuticoRESUMO
Transplanting functional cells to treat myocardial infarction (MI), a major disease threatening human health, has become the focus of global therapy. However, the efficacy has not been well anticipated, partly due to the lack of microvascular system that supplies nutrients and oxygen. Here, spheroids of early vascular cells (EVCs) derived from human embryonic stem cells (hESCs), rather than single-cell forms, as transplant "seeds" for reconstructing microvascular networks, are proposed. Firstly, EVCs containing CD34+ vascular progenitor cells are identified, which effectively differentiate into endothelial cells in situ and form vascular networks in extracellular matrix (ECM) hydrogel. Secondly, cardiac microtissues and cardiac patches with well-organized microvasculature are fabricated by three-dimensional (3D) co-culture or bioprinting with EVCs and cardiomyocytes in hydrogel. Notably, in 3D-bioprinted myocardial models, self-assembly vascularization of EVC spheroids is found to be significantly superior to EVC single cells. EVC spheroids are also injected into ischemic region of MI mouse models to explore its therapeutic potential. These findings uncover hESCs-derived EVC spheroids rather than single cells are more accessible for complex vasculature engineering, which is of great potential for cardiac tissue vascular engineering and MI treatment by cell therapy.
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Bioimpressão , Células-Tronco Embrionárias Humanas , Infarto do Miocárdio , Animais , Bioimpressão/métodos , Células Endoteliais , Humanos , Camundongos , Infarto do Miocárdio/terapia , Engenharia Tecidual/métodosRESUMO
The crystal structure of the title compound, (C(4)H(12)N(2))(2)[BiCl(6)]Cl·H(2)O, consists of piperazinediium cations, [BiCl(6)](3-) anions, Cl(-) anions and uncoordinated water mol-ecules. The Bi(III) cation is coordinated by six Cl(-) anions in a slightly distorted octa-hedral geometry. The diprotonated piperazine ring adopts a chair conformation. In the crystal, extensive inter-molecular N-Hâ¯Cl, N-Hâ¯O and O-Hâ¯Cl hydrogen bonds occur.
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Pancreatic ductal adenocarcinoma (PDAC) is one of most lethal cancers and is projected to be the second leading cause of cancer deaths in the United States by 2030. The lack of effective treatment and increased incidence in PDAC encourage a deeper knowledge of PDAC progression. By analyzing a long noncoding RNA (lncRNA) dataset, we found that increased LINC00941 expression led to poor outcomes in PDAC patients. Furthermore, in vitro and in vivo experiments revealed that LINC00941 promoted PDAC cancer cell growth by enhancing aerobic glycolysis. Mechanistically, LINC00941 was found to interact with mammalian STE20-like protein kinase 1 (MST1), which facilitated the protein phosphatase 2A (PP2A)-mediated dephosphorylation of MST1, resulting in Hippo pathway activation and consequently, enhanced glycolysis in PDAC. These results suggest that LINC00941 plays a key role in regulating PDAC tumorigenesis, potentially highlighting novel avenues for PDAC therapy.
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At present, various fluorescent nanomaterials have been designed and synthesized as optical contrast agents for surgical navigation. However, there have been no reports on the preparation of fluorescent contrast agents for lung cancer surgery navigation using silicon quantum dots (Si QDs). This study improved and modified the water-dispersible Si QD micelles reported by Pi et al. to prepare Si QD micelles-CKAP4. The data showed that the Si QD micelles-CKAP4 were spherical particles with a mean hydrodiameter of approximately 78.8 nm. UV-visible absorption of the Si QD micelles-CKAP4 ranged from 200 to 500 nm. With an excitation wavelength of 330 nm, strong fluorescence at 640 nm was observed in the fluorescence emission spectra. Laser confocal microscopy and fluorescence microscopy assay showed that the Si QD micelles-CKAP4 exhibited good targeting ability to lung cancer cells and lung cancer tissues in vitro. The in vivo fluorescence-imaging assay showed that the Si QD micelles-CKAP4 was metabolized by the liver and excreted by the kidney. In addition, Si QD micelles-CKAP4 specifically targeted lung cancer tissue in vivo compared with healthy lung tissue. Cytotoxicity and hematoxylin and eosin staining assays showed that the Si QD micelles-CKAP4 exhibited high biosafety in vitro and in vivo. Si QD micelles-CKAP4 is a specifically targeted imaging agent for lung cancer and is expected to be a fluorescent contrast agent for lung cancer surgical navigation in the future.
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Objectives: Tumor cells were reported to have perpetual negative surface charges due to elevated glycolysis, and multifunctional nanoprobes (Fe3O4@SiO2, mNPs) could attach onto tumor cells via opposite surface charges. We thus evaluated whether mixing mNPs with urine could improve the sensitivity of urine cytology test (UCT). Methods: We developed a novel UCT method by mixing urine with mNPs (Nano-cytology) to harvest more tumor cells during UCT procedures. The same voided urine sample was divided equally for the Nano-cytology and UCT assay, and evaluated by cytopathologists in a blinded way. The accuracy of UCT, Nano-cytology, and the combination of the two approaches (Nano-UCT) for detecting bladder cancer were determined. Results: Urine samples were prospectively collected from 102 bladder cancer patients and 49 non-cancer participants from June 2020 to February 2021 in Changhai Hospital. Overall sensitivity of the Nano-cytology assay was significantly higher than that of the UCT assay (82.4 vs. 59.8%, p < .01). Sensitivity for low- and high-grade tumors was 79.1% and 39.5% (p < .01) and 84.7% and 74.6% (p = .25) for Nano-cytology and UCT, respectively. Specificity of Nano-cytology was slightly lower than that of UCT (89.8% vs. 100%, p = .022), which is mainly caused by severe urinary tract infection. In addition, Nano-UCT showed increased sensitivity with 90.2% for overall patients, and 83.7% and 94.9% for low- and high-grade tumor, respectively. Conclusion: The Nano-cytology assay had a significantly improved sensitivity compared with UCT for detecting bladder cancer patients. It represents a promising tool for diagnosis of bladder cancer in clinical practice.
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Nanoparticle-mediated photothermal therapy (PTT) has shown promising capability for tumor therapy through the high local temperature at the tumor site generated by a photothermal agent (PTA) under visible or near-infrared (NIR) irradiation. Improving the accumulation of PTA at the tumor site is crucial to achieving effective photothermal treatment. Here, we developed temperature-activatable engineered neutrophils (Ne) by combining indocyanine green (ICG)-loaded magnetic silica NIR-sensitive nanoparticles (NSNP), which provide the potential for dual-targeted photothermal therapy. The combined effect of neutrophil targeting and magnetic targeting increased the accumulation of PTA at the tumor site. According to magnetic resonance imaging (MRI), the retention of intravenous injected NSNP-incorporated neutrophils within the tumor site was markedly augmented as compared to free NSNP. Furthermore, when irradiated by NIR, NSNP could cause a high local temperature at the tumor site and the thermal stimulation of neutrophils. The heat can kill tumor cells directly, and also lead to the death of neutrophils, upon which active substances with tumor-killing efficacy will be released to kill residual tumor cells and thus reduce tumor recurrence. Thereby, our therapy achieved the elimination of malignancy in the mouse model of the pancreatic tumor without recurrence. Given that all materials used in this system have been approved for use in humans, the transition of this treatment method to clinical application is plausible.
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Hipertermia Induzida , Nanopartículas , Ferro , Imageamento por Ressonância Magnética , Neutrófilos , Fototerapia , Terapia FototérmicaRESUMO
Objective: Early identification of coronavirus disease 2019 (COVID-19) patients with worse outcomes may benefit clinical management of patients. We aimed to quantify pneumonia findings on CT at admission to predict progression to critical illness in COVID-19 patients. Methods: This retrospective study included laboratory-confirmed adult patients with COVID-19. All patients underwent a thin-section chest computed tomography (CT) scans showing evidence of pneumonia. CT images with severe moving artifacts were excluded from analysis. Patients' clinical and laboratory data were collected from medical records. Three quantitative CT features of pneumonia lesions were automatically calculated using a care.ai Intelligent Multi-disciplinary Imaging Diagnosis Platform Intelligent Evaluation System of Chest CT for COVID-19, denoting the percentage of pneumonia volume (PPV), ground-glass opacity volume (PGV), and consolidation volume (PCV). According to Chinese COVID-19 guidelines (trial version 7), patients were divided into noncritical and critical groups. Critical illness was defined as a composite of admission to the intensive care unit, respiratory failure requiring mechanical ventilation, shock, or death. The performance of PPV, PGV, and PCV in discrimination of critical illness was assessed. The correlations between PPV and laboratory variables were assessed by Pearson correlation analysis. Results: A total of 140 patients were included, with mean age of 58.6 years, and 85 (60.7%) were male. Thirty-two (22.9%) patients were critical. Using a cutoff value of 22.6%, the PPV had the highest performance in predicting critical illness, with an area under the curve of 0.868, sensitivity of 81.3%, and specificity of 80.6%. The PPV had moderately positive correlation with neutrophil (%) (r = 0.535, p < 0.001), erythrocyte sedimentation rate (r = 0.567, p < 0.001), d-Dimer (r = 0.444, p < 0.001), high-sensitivity C-reactive protein (r = 0.495, p < 0.001), aspartate aminotransferase (r = 0.410, p < 0.001), lactate dehydrogenase (r = 0.644, p < 0.001), and urea nitrogen (r = 0.439, p < 0.001), whereas the PPV had moderately negative correlation with lymphocyte (%) (r = -0.535, p < 0.001). Conclusions: Pneumonia volume quantified on initial CT can non-invasively predict the progression to critical illness in advance, which serve as a prognostic marker of COVID-19.
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BACKGROUND: To develop machine learning classifiers at admission for predicting which patients with coronavirus disease 2019 (COVID-19) who will progress to critical illness. METHODS: A total of 158 patients with laboratory-confirmed COVID-19 admitted to three designated hospitals between December 31, 2019 and March 31, 2020 were retrospectively collected. 27 clinical and laboratory variables of COVID-19 patients were collected from the medical records. A total of 201 quantitative CT features of COVID-19 pneumonia were extracted by using an artificial intelligence software. The critically ill cases were defined according to the COVID-19 guidelines. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to select the predictors of critical illness from clinical and radiological features, respectively. Accordingly, we developed clinical and radiological models using the following machine learning classifiers, including naive bayes (NB), linear regression (LR), random forest (RF), extreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), K-nearest neighbor (KNN), kernel support vector machine (k-SVM), and back propagation neural networks (BPNN). The combined model incorporating the selected clinical and radiological factors was also developed using the eight above-mentioned classifiers. The predictive efficiency of the models is validated using a 5-fold cross-validation method. The performance of the models was compared by the area under the receiver operating characteristic curve (AUC). RESULTS: The mean age of all patients was 58.9±13.9 years and 89 (56.3%) were males. 35 (22.2%) patients deteriorated to critical illness. After LASSO analysis, four clinical features including lymphocyte percentage, lactic dehydrogenase, neutrophil count, and D-dimer and four quantitative CT features were selected. The XGBoost-based clinical model yielded the highest AUC of 0.960 [95% confidence interval (CI): 0.913-1.000)]. The XGBoost-based radiological model achieved an AUC of 0.890 (95% CI: 0.757-1.000). However, the predictive efficacy of XGBoost-based combined model was very close to that of the XGBoost-based clinical model, with an AUC of 0.955 (95% CI: 0.906-1.000). CONCLUSIONS: A XGBoost-based based clinical model on admission might be used as an effective tool to identify patients at high risk of critical illness.
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Modulating the surface properties of nanoparticles (NPs) is an important approach to accomplish immune escape, prolonged the blood retention time, and enhance the ability of targeted drug delivery. The camouflage of cancer cell membrane onto nanoparticles has been proved to be an ideal approach to enhance active targeting ability of NPs. Herein, we isolated the membrane of melanoma cells to coat doxorubicin (DOX) and indocyanine green (ICG)-loaded hollow copper sulfide NPs (ID-HCuSNP@B16F10) for targeted photothermal therapy, photoacoustic imaging, and chemotherapy. A remarkable in vitro anticancer effect after irradiation and homologous targeting can be observed in B16F10 cells after the treatment of ID-HCuSNP@B16F10. Moreover, ID-HCuSNP@B16F10 exhibits excellent photothermal effect in melanoma animal models and achieves a high tumor ablation rate. This biomimetic system can realize high drug loading efficiency, enhanced targeting ability, and ideal antitumor efficiency.
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Melanoma Experimental/terapia , Nanopartículas/química , Técnicas Fotoacústicas , Terapia Fototérmica , Animais , Biomimética , Membrana Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Diagnóstico por Imagem , Tratamento Farmacológico , Humanos , Melanoma Experimental/diagnóstico por imagem , Melanoma Experimental/patologia , Camundongos , Nanopartículas/uso terapêutico , Propriedades de Superfície/efeitos dos fármacosRESUMO
Reactive oxygen species (ROS) play a crucial role in cancer formation and development, especially cancer metastasis. However, lack of a precise tool, which could accurately distinguish specific types of ROS, restricts an in-depth study of ROS in cancer development and progression. Herein, we designed smart and versatile fluorescent Ag nanoclusters (AgNCs) for sensitive and selective detection of different species of ROS in cells and tissues. Methods: Firstly, dual-emission fluorescent AgNCs was synthesized by using bovine serum albumin (BSA) to sense different types of ROS (H2O2, O2â¢-, â¢OH). The responsiveness of the AgNCs to different species of ROS was explored by fluorescence spectrum, hydrodynamic diameter, and so on. Furthermore, dual-emission fluorescent AgNCs was used to sense ROS in tumor with different degrees of differentiation. Finally, the relationship between specific types of ROS and tumor cell invasion was explored by cell migration ability and the expression of cell adhesion and EMT markers. Results: This dual-emission fluorescent AgNCs possessed an excellent ability to sensitively and selectively distinguish highly reactive oxygen species (hROS, including O2â¢-and â¢OH) from moderate reactive oxygen species (the form of H2O2), and exhibited no fluoresence and green fluorescence, respectively. The emission of AgNCs is effective in detecting cellular and tissular ROS. When cultured with AgNCs, malignant tumor cells exhibit non-fluorescence, while the benign tumor emits green and reduced red light and the normal cells appear in weak green and bright red fluorescence. We further verified that not just H2O2 but specific species of ROS (O2â¢-and â¢OH) were involved in cell invasion and malignant transformation. Our study warrants further research on the role of ROS in physiological and pathophysiological processes. Conclusion: Taken together, AgNCs would be a promising approach for sensing ROS, and offer an intelligent tool to detect different kinds of ROS in tumors.
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Técnicas Biossensoriais , Corantes Fluorescentes , Nanopartículas Metálicas , Neoplasias/diagnóstico , Neoplasias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Prata , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Neoplasias/patologia , Fenótipo , Sensibilidade e Especificidade , Soroalbumina Bovina , Espectrometria de FluorescênciaRESUMO
Targeted drug delivery by nanoparticles (NPs) is an essential technique to achieve the ideal therapeutic effect for cancer. However, it requires large amounts of work to imitate the biomarkers on the surface of the cell membrane and cannot fully retain the bio-function and interactions among cells. Cell membranes have been studied to form biomimetic NPs to achieve functions like immune escape, targeted drug delivery, and immune modulation, which inherit the ability to interact with the in vivo environments. Currently, erythrocyte, leukocyte, mesenchymal stem cell, cancer cell and platelet have been applied in coating photothermal agents and anti-cancer drugs to achieve increased photothermal conversion efficiency and decreased side effects in cancer ablation. In this review, we discuss the recent development of cell membrane-coated NPs in the application of photothermal therapy and cancer targeting. The underlying biomarkers of cell membrane-coated nanoparticles (CMNPs) are discussed, and future research directions are suggested.
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Materiais Biomiméticos/química , Membrana Celular/química , Hipertermia Induzida , Nanopartículas/química , Neoplasias/terapia , Fototerapia , Humanos , Nanopartículas/ultraestrutura , Neoplasias/patologiaRESUMO
Prior studies suggest a possibility that the anticancer property of garlic is more effective only when exposed directly to cancer cells than absorbed first by the normal epithelial cells of the gastrointestinal tract wall. We tested this possibility in two mouse models of highly aggressive malignancies that cannot yet be cured by conventional therapies: sarcoma 180- and EL4-induced lethal ascites. Daily oral gavages of raw garlic extract (RGE; equivalent to 100 mg wet weight) for 21 days failed to offer any meaningful effect in the mice with malignancies. However, the daily injection of the same amounts of the same materials for 21 days completely cured all the mice of cancer. This novel anticancer activity of RGE was present entirely in the size fraction of the molecules smaller than 3000 Dalton rather than the larger molecules and was completely partitioned into the organic phase rather than into the aqueous phase. One half of the anticancer activity was inactivated by heating at 100 °C for 10 min, suggesting that multiple components were concertedly involved. In a direct comparison, the RGE was significantly more effective in killing the cultured cancer cells in vitro than the extracts from other 21 raw vegetables and fruits. In cell culture, RGE killed a wide variety of different cancer cells regardless of species of origin and cell types. Cancer cells generally are well known to be defective in many common metabolic pathways present in their normal cell counterpart for processing normal nutrients. The metabolism of these otherwise normal nutrients could be stalled in the cancer cells and become cytotoxic. The most-effective way of treating cancer by RGE may be the direct injection instead of eating the cooked garlic.
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Patients are increasingly being diagnosed with neuropathic diseases, but are rarely cured because of the loss of neurons in damaged tissues. This situation creates an urgent clinical need to develop alternative treatment strategies for effective repair and regeneration of injured or diseased tissues. Neural stem cells (NSCs), highly pluripotent cells with the ability of self-renewal and potential for multidirectional differentiation, provide a promising solution to meet this demand. However, some serious challenges remaining to be addressed are the regulation of implanted NSCs, tracking their fate, monitoring their interaction with and responsiveness to the tissue environment, and evaluating their treatment efficacy. Nanomaterials have been envisioned as innovative components to further empower the field of NSC-based regenerative medicine, because their unique physicochemical characteristics provide unparalleled solutions to the imaging and treatment of diseases. By building on the advantages of nanomaterials, tremendous efforts have been devoted to facilitate research into the clinical translation of NSC-based therapy. Here, recent work on emerging nanomaterials is highlighted and their performance in the imaging and treatment of neurological diseases is evaluated, comparing the strengths and weaknesses of various imaging modalities currently used. The underlying mechanisms of therapeutic efficacy are discussed, and future research directions are suggested.