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1.
Front Endocrinol (Lausanne) ; 15: 1396022, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39290325

RESUMO

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder affecting people worldwide. It is characterized by several key features, including hyperinsulinemia, hyperglycemia, hyperlipidemia, and dysbiosis. Epidemiologic studies have shown that T2DM is closely associated with the development and progression of cancer. T2DM-related hyperinsulinemia, hyperglycemia, and hyperlipidemia contribute to cancer progression through complex signaling pathways. These factors increase drug resistance, apoptosis resistance, and the migration, invasion, and proliferation of cancer cells. Here, we will focus on the role of hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with T2DM in cancer development. Additionally, we will elucidate the potential molecular mechanisms underlying their effects on cancer progression. We aim to identify potential therapeutic targets for T2DM-related malignancies and explore relevant directions for future investigation.


Assuntos
Diabetes Mellitus Tipo 2 , Progressão da Doença , Neoplasias , Humanos , Neoplasias/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Animais , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Hiperinsulinismo/complicações , Hiperinsulinismo/metabolismo , Hiperlipidemias/complicações , Transdução de Sinais
2.
Cancers (Basel) ; 16(15)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39123436

RESUMO

BACKGROUND: Limited data exist on the significance of PET imaging and quantitative PET parameters in primary central nervous system (CNS) lymphoma due to its relative rarity. This study was conducted to investigate the prognostic value of a novel internal standardization indicator, the pontine-white matter (PW) score, in primary CNS lymphoma patients undergoing post-treatment 18F-FDG PET/CT and PET/MR imaging. METHODS: From January 2014 to December 2022, eligible patients with primary CNS lymphoma who underwent post-treatment PET imaging were enrolled. Using the FDG uptake of the pons and white matter as an internal reference, the PW score was graded based on the metabolism of the post-therapeutic lesion for each patient, and its associations with patients' prognosis were investigated. RESULTS: In total, 41 patients with post-treatment PET/CT and 49 patients with post-treatment PET/MR imaging were enrolled. ROC curve analysis indicated that the PW score possessed robust discriminative ability in distinguishing patients with worse outcomes. Furthermore, a higher PW score was significantly correlated with and identified as an independent prognostic indicator for, worse prognosis in both the PET/CT and PET/MR cohorts. CONCLUSION: The study demonstrated that the PW score was an effective prognostic indicator for identifying post-treatment primary CNS lymphoma patients with worse outcomes.

3.
Adv Mater ; : e2401495, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851884

RESUMO

The tumor microenvironment (TME) of typical tumor types such as triple-negative breast cancer is featured by hypoxia and immunosuppression with abundant tumor-associated macrophages (TAMs), which also emerge as potential therapeutic targets for antitumor therapy. M1-like macrophage-derived exosomes (M1-Exos) have emerged as a promising tumor therapeutic candidate for their tumor-targeting and macrophage-polarization capabilities. However, the limited drug-loading efficiency and stability of M1-Exos have hindered their effectiveness in antitumor applications. Here, a hybrid nanovesicle is developed by integrating M1-Exos with AS1411 aptamer-conjugated liposomes (AApt-Lips), termed M1E/AALs. The obtained M1E/AALs are loaded with perfluorotributylamine (PFTBA) and IR780, as P-I, to construct P-I@M1E/AALs for reprogramming TME by alleviating tumor hypoxia and engineering TAMs. P-I@M1E/AAL-mediated tumor therapy enhances the in situ generation of reactive oxygen species, repolarizes TAMs toward an antitumor phenotype, and promotes the infiltration of T lymphocytes. The synergistic antitumor therapy based on P-I@M1E/AALs significantly suppresses tumor growth and prolongs the survival of 4T1-tumor-bearing mice. By integrating multiple treatment modalities, P-I@M1E/AAL nanoplatform demonstrates a promising therapeutic approach for overcoming hypoxic and immunosuppressive TME by targeted TAM reprogramming and enhanced tumor photodynamic immunotherapy. This study highlights an innovative TAM-engineering hybrid nanovesicle platform for the treatment of tumors characterized by hypoxic and immunosuppressive TME.

4.
Nat Nanotechnol ; 19(9): 1386-1398, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38898135

RESUMO

The buildup of plaques in atherosclerosis leads to cardiovascular events, with chronic unresolved inflammation and overproduction of reactive oxygen species (ROS) being major drivers of plaque progression. Nanotherapeutics that can resolve inflammation and scavenge ROS have the potential to treat atherosclerosis. Here we demonstrate the potential of black phosphorus nanosheets (BPNSs) as a therapeutic agent for the treatment of atherosclerosis. BPNSs can effectively scavenge a broad spectrum of ROS and suppress atherosclerosis-associated pro-inflammatory cytokine production in lesional macrophages. We also demonstrate ROS-responsive, targeted-peptide-modified BPNS-based carriers for the delivery of resolvin D1 (an inflammation-resolving lipid mediator) to lesional macrophages, which further boosts the anti-atherosclerotic efficacy. The targeted nanotherapeutics not only reduce plaque areas but also substantially improve plaque stability in high-fat-diet-fed apolipoprotein E-deficient mice. This study presents a therapeutic strategy against atherosclerosis, and highlights the potential of BPNS-based therapeutics to treat other inflammatory diseases.


Assuntos
Aterosclerose , Ácidos Docosa-Hexaenoicos , Macrófagos , Nanoestruturas , Fósforo , Espécies Reativas de Oxigênio , Animais , Humanos , Masculino , Camundongos , Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/patologia , Dieta Hiperlipídica/efeitos adversos , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/química , Ácidos Docosa-Hexaenoicos/administração & dosagem , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Nanoestruturas/química , Fósforo/química , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/patologia , Placa Aterosclerótica/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo
5.
Nanoscale ; 16(15): 7378-7386, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38511468

RESUMO

Tumor-associated macrophages (TAMs) play crucial roles in the immunosuppressive solid tumor microenvironment (TME). Despite their tumor-promoting functions, TAMs can also be therapeutically modulated to exhibit tumor-killing properties, making them attractive targets for tumor immunotherapy. This review highlights the recent advances in nanomedicine-based strategies centered around macrophages for enhanced cancer immunotherapy. Emerging nanomedicine-based strategies to modulate TAMs in cancer treatment include repolarization of the TAM phenotype, inhibition of monocyte recruitment, depletion of TAMs, and blockage of immune checkpoints. These strategies have shown great promise in significantly improving the efficacy of cancer immunotherapy. Moreover, macrophage-inspired drug delivery systems have demonstrated significant promise in inducing immunotherapeutic effects and enhancing therapeutic efficacy by facilitating evasion from the reticuloendothelial system and promoting accumulation at the tumor site. Finally, we also discuss the challenges and propose future opportunities associated with macrophage-modulating nanomedicine to enhance cancer immunotherapy.


Assuntos
Nanomedicina , Neoplasias , Humanos , Macrófagos , Sistema Fagocitário Mononuclear , Neoplasias/patologia , Imunoterapia , Microambiente Tumoral
6.
Small Methods ; : e2301620, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38343178

RESUMO

Acute inflammation has the potential for the recruitment of immune cells, inhibiting tumor angiogenesis, metastasis, and drug resistance thereby overcoming the tumor immunosuppressive microenvironment caused by chronic inflammation. Here, an acute inflammation inducer using bacteria outer membrane vesicles (OMVs) loaded in thermal-sensitive hydrogel (named OMVs-gel) for localized and controlled release of OMVs in tumor sites is proposed. OMVs trigger neutrophil recruitment and amplify acute inflammation inside tumor tissues. The hydrogel ensures drastic inflammation is confined within the tumor, addressing biosafety concerns that the direct administration of free OMVs may cause fatal effects. This strategy eradicated solid tumors safely and rapidly. The study further elucidates one of the possible immune mechanisms of OMVs-gel therapy, which involves the assembly of antitumor neutrophils and elastase release for selective tumor killing. Additionally, tumor vascular destruction induced by OMVs-gel results in tumor darkening, allowing for combinational photothermal therapy. The findings suggest that the use of OMVs-gel can safely induce acute inflammation and enhance antitumor immunity, representing a promising strategy to promote acute inflammation application in tumor immunotherapy.

7.
Electrophoresis ; 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37909658

RESUMO

Single-cell biophysical properties play a crucial role in regulating cellular physiological states and functions, demonstrating significant potential in the fields of life sciences and clinical diagnostics. Therefore, over the last few decades, researchers have developed various detection tools to explore the relationship between the biophysical changes of biological cells and human diseases. With the rapid advancement of modern microfabrication technology, microfluidic devices have quickly emerged as a promising platform for single-cell analysis offering advantages including high-throughput, exceptional precision, and ease of manipulation. Consequently, this paper provides an overview of the recent advances in microfluidic analysis and detection systems for single-cell biophysical properties and their applications in the field of cancer. The working principles and latest research progress of single-cell biophysical property detection are first analyzed, highlighting the significance of electrical and mechanical properties. The development of data acquisition and processing methods for real-time, high-throughput, and practical applications are then discussed. Furthermore, the differences in biophysical properties between tumor and normal cells are outlined, illustrating the potential for utilizing single-cell biophysical properties for tumor cell identification, classification, and drug response assessment. Lastly, we summarize the limitations of existing microfluidic analysis and detection systems in single-cell biophysical properties, while also pointing out the prospects and future directions of their applications in cancer diagnosis and treatment.

8.
Nat Commun ; 14(1): 6973, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37914681

RESUMO

The dense stroma of desmoplastic tumor limits nanotherapeutic penetration and hampers the antitumor immune response. Here, we report a denaturation-and-penetration strategy and the use of tin monosulfide nanoparticles (SnSNPs) as nano-sonosensitizers that can overcome the stromal barrier for the management of desmoplastic triple-negative breast cancer (TNBC). SnSNPs possess a narrow bandgap (1.18 eV), allowing for efficient electron (e-)-hole (h+) pair separation to generate reactive oxygen species under US activation. More importantly, SnSNPs display mild photothermal properties that can in situ denature tumor collagen and facilitate deep penetration into the tumor mass upon near-infrared irradiation. This approach significantly enhances sonodynamic therapy (SDT) by SnSNPs and boosts antitumor immunity. In mouse models of malignant TNBC and hepatocellular carcinoma (HCC), the combination of robust SDT and enhanced cytotoxic T lymphocyte infiltration achieves remarkable anti-tumor efficacy. This study presents an innovative approach to enhance SDT and antitumor immunity using the denaturation-and-penetration strategy, offering a potential combined sono-immunotherapy approach for the cancer nanomedicine field.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Neoplasias , Neoplasias de Mama Triplo Negativas , Terapia por Ultrassom , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/terapia , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias Hepáticas/terapia , Neoplasias/terapia , Espécies Reativas de Oxigênio , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral
9.
Proc Natl Acad Sci U S A ; 120(44): e2304966120, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37878720

RESUMO

Messenger RNA (mRNA)-based therapeutics are transforming the landscapes of medicine, yet targeted delivery of mRNA to specific cell types while minimizing off-target accumulation remains challenging for mRNA-mediated therapy. In this study, we report an innovative design of a cationic lipid- and hyaluronic acid-based, dual-targeted mRNA nanoformulation that can display the desirable stability and efficiently transfect the targeted proteins into lung tissues. More importantly, the optimized dual-targeted mRNA nanoparticles (NPs) can not only accumulate primarily in lung tumor cells and inflammatory macrophages after inhalation delivery but also efficiently express any desirable proteins (e.g., p53 tumor suppressor for therapy, as well as luciferase and green fluorescence protein for imaging as examples in this study) and achieve efficacious lung tissue transfection in vivo. Overall, our findings provide proof-of-principle evidence for the design and use of dual-targeted mRNA NPs in homing to specific cell types to up-regulate target proteins in lung tissues, which may hold great potential for the future development of mRNA-based inhaled medicines or vaccines in treating various lung-related diseases.


Assuntos
Nanopartículas , Neoplasias , RNA Mensageiro/genética , Transfecção , Pulmão , Macrófagos
10.
Front Immunol ; 14: 1140463, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37600773

RESUMO

Immunotherapy has been emerging as a powerful strategy for cancer management. Recently, accumulating evidence has demonstrated that bacteria-based immunotherapy including naive bacteria, bacterial components, and bacterial derivatives, can modulate immune response via various cellular and molecular pathways. The key mechanisms of bacterial antitumor immunity include inducing immune cells to kill tumor cells directly or reverse the immunosuppressive microenvironment. Currently, bacterial antigens synthesized as vaccine candidates by bioengineering technology are novel antitumor immunotherapy. Especially the combination therapy of bacterial vaccine with conventional therapies may further achieve enhanced therapeutic benefits against cancers. However, the clinical translation of bacteria-based immunotherapy is limited for biosafety concerns and non-uniform production standards. In this review, we aim to summarize immunotherapy strategies based on advanced bacterial therapeutics and discuss their potential for cancer management, we will also propose approaches for optimizing bacteria-based immunotherapy for facilitating clinical translation.


Assuntos
Imunoterapia , Neoplasias , Humanos , Bactérias , Neoplasias/terapia , Antígenos de Bactérias , Vacinas Bacterianas , Microambiente Tumoral
11.
Angew Chem Int Ed Engl ; 62(41): e202308413, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37380606

RESUMO

Tumor-associated macrophages (TAMs) play a critical role in the immunosuppressive solid tumor microenvironment (TME), yet in situ engineering of TAMs for enhanced tumor immunotherapy remains a significant challenge in translational immuno-oncology. Here, we report an innovative nanodrug-delivering-drug (STNSP@ELE) strategy that leverages two-dimensional (2D) stanene-based nanosheets (STNSP) and ß-Elemene (ELE), a small-molecule anticancer drug, to overcome TAM-mediated immunosuppression and improve chemo-immunotherapy. Our results demonstrate that both STNSP and ELE are capable of polarizing the tumor-supportive M2-like TAMs into a tumor-suppressive M1-like phenotype, which acts with the ELE chemotherapeutic to boost antitumor responses. In vivo mouse studies demonstrate that STNSP@ELE treatment can reprogram the immunosuppressive TME by significantly increasing the intratumoral ratio of M1/M2-like TAMs, enhancing the population of CD4+ and CD8+ T lymphocytes and mature dendritic cells, and elevating the expression of immunostimulatory cytokines in B16F10 melanomas, thereby promoting a robust antitumor response. Our study not only demonstrates that the STNSP@ELE chemo-immunotherapeutic nanoplatform has immune-modulatory capabilities that can overcome TAM-mediated immunosuppression in solid tumors, but also highlights the promise of this nanodrug-delivering-drug strategy in developing other nano-immunotherapeutics and treating various types of immunosuppressive tumors.


Assuntos
Melanoma , Nanopartículas , Neoplasias , Camundongos , Animais , Macrófagos Associados a Tumor , Macrófagos/metabolismo , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Melanoma/patologia , Nanopartículas/uso terapêutico , Microambiente Tumoral
12.
J Am Chem Soc ; 145(22): 12193-12205, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37208802

RESUMO

Selenoprotein plays a crucial role in immune cells and inflammatory regulation. However, as a protein drug that is easily denatured or degraded in the acidic environment of the stomach, efficient oral delivery of selenoprotein is a great challenge. Herein, we innovated an oral hydrogel microbeads-based biochemical strategy that can in situ synthesize selenoproteins, therefore bypassing the necessity and harsh conditions for oral protein delivery while effectively generating selenoproteins for therapeutic applications. The hydrogel microbeads were synthesized by coating hyaluronic acid-modified selenium nanoparticles with a protective shell of calcium alginate (SA) hydrogel. We tested this strategy in mice with inflammatory bowel disease (IBD), one of the most representative diseases related to intestinal immunity and microbiota. Our results revealed that hydrogel microbeads-mediated in situ synthesis of selenoproteins could prominently reduce proinflammatory cytokines secretion and mediate immune cells (e.g., reduce neutrophils and monocytes and increase immune regulatory T cells) to effectively relieve colitis-associated symptoms. This strategy was also able to regulate gut microbiota composition (increase probiotics abundance and suppress detrimental communities) to maintain intestinal homeostasis. Considering intestinal immunity and microbiota widely associated with cancers, infections, inflammations, etc., this in situ selenoprotein synthesis strategy might also be possibly applied to broadly tackle various diseases.


Assuntos
Hidrogéis , Microbiota , Animais , Camundongos , Microesferas , Selenoproteínas/metabolismo , Inflamação
13.
J Am Chem Soc ; 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36930579

RESUMO

Because of tumor heterogeneity and the immunosuppressive tumor microenvironment, most cancer vaccines typically do not elicit robust antitumor immunological responses in clinical trials. In this paper, we report findings about a bioadhesive nanoparticle (BNP)-based separable cancer vaccine, FeSHK@B-ovalbumin (OVA), to target multi-epitope antigens and exert effective cancer immunotherapy. After the FeSHK@B-OVA "nanorocket" initiates the "satellite-rocket separation" procedure in the acidic tumor microenvironment, the FeSHK@B "launch vehicle" can amplify intracellular oxidative stress persistently. This procedure allows for bioadhesiveness-mediated prolonged drug retention within the tumor tissue and triggers the immunogenic death of tumor cells that transforms the primary tumors into antigen depots, which acts synergistically with the OVA "satellite" to trigger robust antigen-specific antitumor immunity. The cooperation of these two immunostimulants not only efficiently inhibits the primary tumor growth and provokes durable antigen-specific immune activation in vivo but also activates a long-term and robust immune memory effect to resist tumor rechallenge and metastasis. These results highlight the enormous potential of FeSHK@B-OVA to serve as an excellent therapeutic and prophylactic cancer nanovaccine. By leveraging the antigen depots in situ and the synergistic effect among multi-epitope antigens, such a nanovaccine strategy with stealthy bioadhesion may offer a straightforward and efficient approach to developing various cancer vaccines for different types of tumors.

14.
Biomaterials ; 295: 122031, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36731367

RESUMO

This study reports an ultrasound-mediated and two-dimensional (2D) porous vermiculite nanosheets (VMT NSs)-based nanocatalyst platform (Arg@VMT@PDA-PEG) that synergistically harnessed the Fenton reaction-based chemodynamic therapy (CDT), 2D semiconductor-based sonodynamic therapy (SDT) and nitric oxide (NO)-based gas therapy for combination cancer therapy. The tumor microenvironment responsive degradation of polydopamine (PDA) shell could not only prevent L-Arg, a NO donor, leakage during blood circulation, but also selectively release the active sites of VMT NSs for catalytic reactions in tumor cells. Additionally, the Fenton reactions mediated by the abundant Fe2+/Fe3+ in VMT NSs could efficiently produce ·OH and consume glutathione (GSH) for CDT. Moreover, the reactive oxygen species (ROS, ·OH and ·O2-) produced by ultrasound-triggered Arg@VMT@PDA-PEG could not only execute SDT but also oxidize L-Arg to NO for synergetic gas therapy. The results show that the transformation of ROS to NO can enhance curative efficacy owing to the ability of NO with much longer life-time in freely diffusing into cells from intercellular space. This biodegradable Arg@VMT@PDA-PEG nanocatalytic platform integrating three different catalytic reactions provides a new therapeutic paradigm for combination cancer therapy.


Assuntos
Arginina , Neoplasias , Humanos , Porosidade , Espécies Reativas de Oxigênio , Terapia Combinada , Glutationa , Óxido Nítrico , Linhagem Celular Tumoral , Microambiente Tumoral , Peróxido de Hidrogênio
15.
Bioact Mater ; 20: 548-560, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35846843

RESUMO

Bacterial outer membrane vesicles (OMVs) are potent immuno-stimulating agents and have the potentials to be bioengineered as platforms for antitumor nanomedicine. In this study, OMVs are demonstrated as promising antitumor therapeutics. OMVs can lead to beneficial M2-to-M1 polarization of macrophages and induce pyroptosis to enhance antitumor immunity, but the therapeutic window of OMVs is narrow for its toxicity. We propose a bioengineering strategy to enhance the tumor-targeting ability of OMVs by macrophage-mediated delivery and improve the antitumor efficacy by co-loading of photosensitizer chlorin e6 (Ce6) and chemotherapeutic drug doxorubicin (DOX) into OMVs as a therapeutic platform. We demonstrate that systemic injection of the DOX/Ce6-OMVs@M therapeutic platform, providing combinational photodynamic/chemo-/immunotherapy, eradicates triple-negative breast tumors in mice without side effects. Importantly, this strategy also effectively prevents tumor metastasis to the lung. This OMVs-based strategy with bioengineering may serve as a powerful therapeutic platform for a synergic antitumor therapy.

16.
Anal Methods ; 14(46): 4813-4821, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36382629

RESUMO

The mechanical properties of single cells have been recognized as biomarkers for identifying individual cells and diagnosing human diseases. Microfluidic devices based on the flow cytometry principle, which are not limited by the vision field of a microscope and can achieve a very high throughput, have been extensively adopted to measure the mechanical properties of single cells. However, these kinds of microfluidic devices usually required pressure-driven pumps with a very low flow rate and high precision. In this study, we developed a high-throughput microfluidic device inspired by the Wheatstone bridge principle for characterizing the mechanical properties of single cells. The microfluidic analogue of the Wheatstone bridge not only took advantage of flow cytometry, but also allowed precise control of a very low flow rate through the constricted channel with a higher input flow rate generated by a commercially available pressure-driven pump. Under different input flow rates of the pump, the apparent elastic moduli and the fluidity of osteosarcoma (U-2OS) cells and cervical carcinoma (HeLa) cells were measured by monitoring their dynamic deformations passing through the bridge-channel with different sizes of rectangular constrictions. The results showed that the input flow rate had little effect on measuring the mechanical properties of the cells, while the ratio of cell radius to effective constriction radius was different, i.e., for U-2OS cells it was 1.20 and for HeLa cells it was 1.09. Under this condition compared with predecessors, our statistic results of cell mechanical properties exhibited minimal errors. Furthermore, the cell viability after measurements was kept above 90% that demonstrated the non-destructive property of our proposed method.


Assuntos
Técnicas Analíticas Microfluídicas , Humanos , Técnicas Analíticas Microfluídicas/métodos , Microfluídica , Células HeLa , Dispositivos Lab-On-A-Chip , Citometria de Fluxo/métodos
17.
Acta Biochim Pol ; 69(3): 551-557, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35767742

RESUMO

There is concrete evidence that lncRNA-MINCR is involved in tumorigenesis of a number of human cancers through modulation of Wnt/ß-catenin signaling pathway. However, the characterization of regulatory role of lncRNA-MINCR has not been worked out in osteosarcoma yet. The present study was undertaken to explore the role of lncRNA-MINCR in human osteosarcoma. The osteosarcoma tissues and cell lines were found to exhibit significant (P<0.05) over-expression of lncRNA-MINCR. Silencing of lncRNA-MINCR in osteosarcoma cells suppressed their cell viability through the induction of apoptosis. The Saos-2 osteosarcoma cells exhibited significant (P<0.05) decline in migration and invasion rate together with inhibition of EMT under transcriptional knockdown of lncRNA-MINCR. Western blot analysis revealed that lncRNA-MINCR operated through Wnt/ß-catenin signaling pathway to control the growth and metastasis of osteosarcoma cells. In vivo mice tumorigenesis was significantly (P<0.05) restricted under lncRNA-MINCR repression. The study clearly indicated that lncRNA-MINCR exhibits crucial growth regulatory role in osteosarcoma together with its ability to control the metastasis of cancer cells through Wnt/ß-catenin signal.


Assuntos
Neoplasias Ósseas , Osteossarcoma , RNA Longo não Codificante , Animais , Apoptose/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Osteossarcoma/genética , Osteossarcoma/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Via de Sinalização Wnt/genética , beta Catenina/genética , beta Catenina/metabolismo
18.
Front Bioeng Biotechnol ; 10: 812277, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35284414

RESUMO

Central nervous system leukemia (CNS-L) is caused by leukemic cells infiltrating into the meninges or brain parenchyma and remains the main reason for disease relapse. Currently, it is hard to detect CNS-L accurately by clinically available imaging models due to the relatively low amount of tumor cells, confined blood supply, and the inferior glucose metabolism intensity. Recently, integrin α6-laminin interactions have been identified to mediate CNS-L, which suggests that integrin α6 may be a promising molecular imaging target for the detection of CNS-L. The acute lymphoblastic leukemia (ALL) cell line NALM6 stabled and transfected with luciferase was used to establish the CNS-L mouse model. CNS-L-bearing mice were monitored and confirmed by bioluminescence imaging. Three of our previously developed integrin α6-targeted peptide-based molecular imaging agents, Cy5-S5 for near-infrared fluorescence (NIRF), Gd-S5 for magnetic resonance (MR), and 18F-S5 for positron emission tomography (PET) imaging, were employed for the molecular imaging of these CNS-L-bearing mice. Bioluminescence imaging showed a local intensive signal in the heads among CNS-L-bearing mice; meanwhile, Cy5-S5/NIRF imaging produced intensive fluorescence intensity in the same head regions. Moreover, Gd-S5/MR imaging generated superior MR signal enhancement at the site of meninges, which were located between the skull bone and brain parenchyma. Comparatively, MR imaging with the clinically available MR enhancer Gd-DTPA did not produce the distinguishable MR signal in the same head regions. Additionally, 18F-S5/PET imaging also generated focal radio-concentration at the same head regions, which generated nearly 5-times tumor-to-background ratio compared to the clinically available PET radiotracer 18F-FDG. Finally, pathological examination identified layer-displayed leukemic cells in the superficial part of the brain parenchyma tissue, and immunohistochemical staining confirmed the overexpression of the integrin α6 within the lesion. These findings suggest the potential application of these integrin α6-targeted molecular imaging agents for the accurate detection of CNS-L.

19.
Int J Nanomedicine ; 17: 837-854, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35228800

RESUMO

PURPOSE: In order to prepare a biomimetic nano-carrier which has inflammatory chemotaxis, homologous targeting and reduce immune clearance, for targeted chemotherapy of osteosarcoma, we fabricated the paclitaxel-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with 143B-RAW hybrid membrane (PTX-PLGA@[143B-RAW] NPs) and evaluate its anti-cancer efficacy in vitro and vivo. METHODS: PTX-PLGA@[143B-RAW] NPs were prepared by the ultrasonic method and were characterized by size, zeta potential, polymer dispersion index (PDI), Coomassie bright blue staining, transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC). Cellular uptake, cell viability assay, flow cytometry and chemotactic effect of PTX-PLGA@[143B-RAW] NPs were evaluated in vitro. Biodistribution, anti-cancer therapeutic efficacy and safety of PTX-PLGA@[143B-RAW] NPs were evaluated in 143B osteosarcoma xenograft mice. RESULTS: The hybrid membrane successfully coated onto the surface of PLGA nanoparticles. PTX-PLGA@[143B-RAW] NPs had a drug loading capacity of 4.24 ± 0.02% and showed targeting ability to osteosarcoma. PTX-PLGA@[143B-RAW] NPs showed high cellular uptake and improved anti-cancer efficacy against 143B cells. More importantly, PTX-PLGA@[143B-RAW] NPs treatment suppressed tumor growth in tumor-bearing mice with minimal damage to normal tissues. CONCLUSION: PTX-PLGA@[143B-RAW] NPs could be used for targeted drug delivery and osteosarcoma therapy.


Assuntos
Neoplasias Ósseas , Nanopartículas , Osteossarcoma , Animais , Biomimética , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , Membrana Celular , Portadores de Fármacos/química , Humanos , Ácido Láctico/química , Camundongos , Nanopartículas/química , Osteossarcoma/tratamento farmacológico , Paclitaxel , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Distribuição Tecidual
20.
Acta Pharm Sin B ; 12(5): 2206-2223, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35013704

RESUMO

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation, antigen assembly, and antigen presentation; they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal. In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.

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