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1.
Nano Lett ; 24(19): 5690-5698, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38700237

RESUMO

Long-term tumor starvation may be a potential strategy to elevate the antitumor immune response by depriving nutrients. However, combining long-term starvation therapy with immunotherapy often yields limited efficacy due to the blockage of immune cell migration pathways. Herein, an intelligent blood flow regulator (BFR) is first established through photoactivated in situ formation of the extravascular dynamic hydrogel to compress blood vessels, which can induce long-term tumor starvation to elicit metabolic stress in tumor cells without affecting immune cell migration pathways. By leveraging methacrylate-modified nanophotosensitizers (HMMAN) and biodegradable gelatin methacrylate (GelMA), the developed extravascular hydrogel dynamically regulates blood flow via enzymatic degradation. Additionally, aPD-L1 loaded into HMMAN continuously blocks immune checkpoints. Systematic in vivo experiments demonstrate that the combination of immune checkpoint blockade (ICB) and BFR-induced metabolic stress (BIMS) significantly delays the progression of Lewis lung and breast cancers by reshaping the tumor immunogenic landscape and enhancing antitumor immune responses.


Assuntos
Hidrogéis , Hidrogéis/química , Animais , Camundongos , Humanos , Linhagem Celular Tumoral , Feminino , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Imunoterapia , Gelatina/química , Metacrilatos/química , Metacrilatos/farmacologia , Neoplasias da Mama/imunologia
2.
J Colloid Interface Sci ; 668: 646-657, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38696992

RESUMO

Severe spinal cord injury (SCI) leads to dysregulated neuroinflammation and cell apoptosis, resulting in axonal die-back and the loss of neuroelectric signal transmission. While biocompatible hydrogels are commonly used in SCI repair, they lack the capacity to support neuroelectric transmission. To overcome this limitation, we developed an injectable silk fibroin/ionic liquid (SFMA@IL) conductive hydrogel to assist neuroelectric signal transmission after SCI in this study. The hydrogel can form rapidly in situ under ultraviolet (UV) light. The mechanical supporting and neuro-regenerating properties are provided by silk fibroin (SF), while the conductive capability is provided by the designed ionic liquid (IL). SFMA@IL showed attractive features for SCI repair, such as anti-swelling, conductivity, and injectability. In vivo, SFMA@IL hydrogel used in rats with complete transection injuries was found to remodel the microenvironment, reduce inflammation, and facilitate neuro-fiber outgrowth. The hydrogel also led to a notable decrease in cell apoptosis and the achievement of scar-free wound healing, which saved 45.6 ± 10.8 % of spinal cord tissue in SFMA@IL grafting. Electrophysiological studies in rats with complete transection SCI confirmed SFMA@IL's ability to support sensory neuroelectric transmission, providing strong evidence for its signal transmission function. These findings provide new insights for the development of effective SCI treatments.


Assuntos
Condutividade Elétrica , Fibroínas , Hidrogéis , Ratos Sprague-Dawley , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/patologia , Animais , Ratos , Hidrogéis/química , Hidrogéis/farmacologia , Fibroínas/química , Fibroínas/farmacologia , Injeções , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Tamanho da Partícula
3.
Nat Mater ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594486

RESUMO

DNA origami is capable of spatially organizing molecules into sophisticated geometric patterns with nanometric precision. Here we describe a reconfigurable, two-dimensional DNA origami with geometrically patterned CD95 ligands that regulates immune cell signalling to alleviate rheumatoid arthritis. In response to pH changes, the device reversibly transforms from a closed to an open configuration, displaying a hexagonal pattern of CD95 ligands with ~10 nm intermolecular spacing, precisely mirroring the spatial arrangement of CD95 receptor clusters on the surface of immune cells. In a collagen-induced arthritis mouse model, DNA origami elicits robust and selective activation of CD95 death-inducing signalling in activated immune cells located in inflamed synovial tissues. Such localized immune tolerance ameliorates joint damage with no noticeable side effects. This device allows for the precise spatial control of cellular signalling, expanding our understanding of ligand-receptor interactions and is a promising platform for the development of pharmacological interventions targeting these interactions.

4.
Small ; : e2400353, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651235

RESUMO

Chemotherapy is crucial in oncology for combating malignant tumors but often encounters obatacles such as severe adverse effects, drug resistance, and biocompatibility issues. The advantages of degradable silica nanoparticles in tumor diagnosis and treatment lie in their ability to target drug delivery, minimizing toxicity to normal tissues while enhancing therapeutic efficacy. Moreover, their responsiveness to both endogenous and exogenous stimuli opens up new possibilities for integrating multiple treatment modalities. This review scrutinizes the burgeoning utility of degradable silica nanoparticles in combination with chemotherapy and other treatment modalities. Commencing the elucidation of degradable silica synthesis and degradation mechanisms, emphasis is placed on the responsiveness of these materials to endogenous (e.g., pH, redox reactions, hypoxia, and enzymes) and exogenous stimuli (e.g., light and high-intensity focused ultrasound). Moreover, this exploration delves into strategies harnessing degradable silica nanoparticles in chemotherapy alone, coupled with radiotherapy, photothermal therapy, photodynamic therapy, gas therapy, immunotherapy, starvation therapy, and chemodynamic therapy, elucidating multimodal synergies. Concluding with an assessment of advances, challenges, and constraints in oncology, despite hurdles, future investigations are anticipated to augment the role of degradable silica in cancer therapy. These insights can serve as a compass for devising more efficacious combined tumor treatment strategies.

5.
Adv Sci (Weinh) ; 11(21): e2308719, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38520727

RESUMO

Traumatic brain injuries (TBI) and stroke are major causes of morbidity and mortality in both developing and developed countries. The complex and heterogeneous pathophysiology of TBI and cerebral ischemia-reperfusion injury (CIRI), in addition to the blood-brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)-responsive neutrophil-targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.


Assuntos
Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , Armadilhas Extracelulares , Neutrófilos , Acidente Vascular Cerebral , Armadilhas Extracelulares/metabolismo , Neutrófilos/metabolismo , Animais , Camundongos , Proteína-Arginina Desiminase do Tipo 4/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Masculino , Nanomedicina Teranóstica/métodos
6.
Adv Mater ; 35(48): e2303149, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37691545

RESUMO

Pharmacological activation of the stimulator of interferon genes (STING) pathway has become a promising strategy for cancer immunotherapy. However, the insufficient tumorous accumulation, rapid clearance, and short duration of drug efficacy in the tumor microenvironment of small structural STING agonists greatly compromise the therapeutic efficacy. Herein, a tumorous extracellular matrix (ECM) is presented anchoring STING agonist-based photoimmunothernostic nanomedicine (SAPTN) that can be activated by mild-temperature photothermal therapy (mild PTT) induced neutrophilic inflammation. The SAPTN owns second window near-infrared (NIR-II) photonics properties fitting for NIR-II fluorescence and photoacoustic imaging-guided cancer therapy. The aggregates SAPTN targeting to the ECM provide slow and continuous release of potent STING agonists diABZIs. The mild PTT and long-lasting STING agonists released in the ECM synergistically prime systematic, robust, and long-term anticancer immunity. In a tumor model, this approach leads to complete tumor eradication in about 100% of mice with orthotopic breast tumors, and the mice regained tumor-free survival of at least 2 months. In addition, the immune-mediated abscopal effect shows inhibition of the distant solid tumor growth by intratumoral administration of SAPTN with laser irradiation. Overall, this approach represents a generalized photoactivable nanomedicine to prime anticancer immunity for improved cancer theranostics.


Assuntos
Nanopartículas , Neoplasias , Camundongos , Animais , Terapia Fototérmica , Neoplasias/terapia , Nanomedicina , Linhagem Celular Tumoral , Fototerapia , Nanopartículas/química , Nanomedicina Teranóstica , Microambiente Tumoral
7.
J Med Chem ; 66(11): 7438-7453, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37220310

RESUMO

Abnormal activation of fibroblast growth factor receptors (FGFRs) results in the development and progression of human cancers. FGFR2 is frequently amplified or mutated in cancers; therefore, it is an attractive target for tumor therapy. Despite the development of several pan-FGFR inhibitors, their long-term therapeutic efficacy is hindered by acquired mutations and low isoform selectivity. Herein, we report the discovery of an efficient and selective FGFR2 proteolysis-targeting chimeric molecule, LC-MB12, that incorporates an essential rigid linker. LC-MB12 preferentially internalizes and degrades membrane-bound FGFR2 among the four FGFR isoforms; this may promote greater clinical benefits. LC-MB12 exhibits superior potency in FGFR signaling suppression and anti-proliferative activity compared to the parental inhibitor. Furthermore, LC-MB12 is orally bioavailable and shows significant antitumor effects in FGFR2-dependent gastric cancer in vivo. Taken together, LC-MB12 is a candidate FGFR2 degrader for alternative FGFR2-targeting strategies and offers a promising starting point for drug development.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Mutação , Transdução de Sinais , Inibidores de Proteínas Quinases/farmacologia , Fosforilação , Linhagem Celular Tumoral
8.
Adv Sci (Weinh) ; 10(19): e2301348, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37078794

RESUMO

Ischemic stroke is a refractory disease that endangers human health and safety owing to cerebral ischemia. Brain ischemia induces a series of inflammatory reactions. Neutrophils migrate from the circulatory system to the site of cerebral ischemia and accumulate in large numbers at the site of inflammation across the blood-brain barrier. Therefore, hitchhiking on neutrophils to deliver drugs to ischemic brain sites could be an optimal strategy. Since the surface of neutrophils has a formyl peptide receptor (FPR), this work modifies a nanoplatform surface by the peptide cinnamyl-F-(D)L-F-(D)L-F (CFLFLF), which can specifically bind to the FPR receptor. After intravenous injection, the fabricated nanoparticles effectively adhered to the surface of neutrophils in peripheral blood mediated by FPR, thereby hitchhiking with neutrophils to achieve higher accumulation at the inflammatory site of cerebral ischemia. In addition, the nanoparticle shell is composed of a polymer with reactive oxygen species (ROS)-responsive bond breaking and is encased in ligustrazine, a natural product with neuroprotective properties. In conclusion, the strategy of hitching the delivered drugs to neutrophils in this study could improve drug enrichment in the brain, thereby providing a general delivery platform for ischemic stroke or other inflammation-related diseases.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Nanopartículas , Traumatismo por Reperfusão , Humanos , Neutrófilos/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , AVC Isquêmico/metabolismo
9.
Angew Chem Int Ed Engl ; 62(35): e202300379, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-36828775

RESUMO

Understanding the intricate molecular machinery that governs ferroptosis and leveraging this accumulating knowledge could facilitate disease prevention, diagnosis, treatment, and prognosis. Emerging approaches for the in situ detection of the major regulators and biological events across cellular, tissue, and in living subjects provide a multiscale perspective for studying ferroptosis. Furthermore, advanced applications that integrate ferroptosis detection and the latest technologies hold tremendous promise in ferroptosis research. In this review, we first briefly summarize the mechanisms and key regulators underlying ferroptosis. Ferroptosis detection approaches are then presented to delineate their design, mechanisms of action, and applications. Special interest is placed on advanced ferroptosis applications that integrate multifunctional platforms. Finally, we discuss the prospects and challenges of ferroptosis detection approaches and applications, with the aim of providing a roadmap for the theranostic development of a broad range of ferroptosis-related diseases.


Assuntos
Ferroptose , Humanos
10.
Nano Res ; 16(2): 2660-2671, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36405982

RESUMO

A bioresponsive polymeric nanocarrier for drug delivery is able to alter its physical and physicochemical properties in response to a variety of biological signals and pathological changes, and can exert its therapeutic efficacy within a confined space. These nanosystems can optimize the biodistribution and subcellular location of therapeutics by exploiting the differences in biochemical properties between tumors and normal tissues. Moreover, bioresponsive polymer-based nanosystems could be rationally designed as precision therapeutic platforms by optimizing the combination of responsive elements and therapeutic components according to the patient-specific disease type and stage. In this review, recent advances in smart bioresponsive polymeric nanosystems for cancer chemotherapy and immunotherapy will be summarized. We mainly discuss three categories, including acidity-sensitive, redox-responsive, and enzyme-triggered polymeric nanosystems. The important issues regarding clinical translation such as reproducibility, manufacture, and probable toxicity, are also commented.

11.
Front Bioeng Biotechnol ; 10: 1022330, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204469

RESUMO

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Emerging therapies, such as ferroptosis mediated cancer therapy and phototherapy, offer new opportunities for HCC treatment. The combination of multiple treatments is often more effective than monotherapy, but many of the current treatments are prone to serious side effects, resulting in a serious decline in patients' quality of life. Therefore, the combination therapy of tumor in situ controllable activation will improve the efficacy and reduce side effects for precise treatment of tumor. Herein, we synthesized a GSH-activatable nanomedicine to synergize photothermal therapy (PTT) and ferrotherapy. We utilized a near-infrared dye SQ890 as both an iron-chelating and a photothermal converter agent, which was encapsulated with a GSH-sensitive polymer (PLGA-SS-mPEG), to attain the biocompatible SQ890@Fe nanoparticles (NPs). In the tumor microenvironment (TME), SQ890@Fe NPs showed a GSH-activated photothermal effect that could increase the Fenton reaction rate. Meanwhile, the depletion of GSH could further increase ferroptosis effect. In turn, the increasing radical generated by ferrotherapy could impair the formation of heat shock proteins (HSPs) which could amplify PTT effects by limiting the self-protection mechanism. Overall, the intelligent nanomedicine SQ890@Fe NPs combines ferrotherapy and PTT to enhance the efficacy and safety of cancer treatment through the mutual promotion of the two treatment mechanisms, providing a new dimension for tumor combination therapy.

12.
Acta Biomater ; 154: 23-48, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36243371

RESUMO

Osteoarthritis (OA) is a degenerative joint disease and is the main cause of chronic pain and functional disability in adults. Articular cartilage is a hydrated soft tissue that is composed of normally quiescent chondrocytes at a low density, a dense network of collagen fibrils with a pore size of 60-200 nm, and aggrecan proteoglycans with high-density negative charge. Although certain drugs, nucleic acids, and proteins have the potential to slow the progression of OA and restore the joints, these treatments have not been clinically applied owing to the lack of an effective delivery system capable of breaking through the cartilage barrier. Recently, the development of nanotechnology for delivery systems renders new ideas and treatment methods viable in overcoming the limited penetration. In this review, we focus on current research on such applications of nanotechnology, including exosomes, protein-based cationic nanocarriers, cationic liposomes/solid lipid nanoparticles, amino acid-based nanocarriers, polyamide derivatives-based nanocarriers, manganese dioxide, and carbon nanotubes. Exosomes are the smallest known nanoscale extracellular vesicles, and they can quickly deliver nucleic acids or proteins to the required depth. Through electrostatic interactions, nanocarriers with appropriate balance in cationic property and particle size have a strong ability to penetrate cartilage. Although substantial preclinical evidence has been obtained, further optimization is necessary for clinical transformation. STATEMENT OF SIGNIFICANCE: The dense cartilage matrix with high-negative charge was associated with reduced therapeutic effect in osteoarthritis patients with deep pathological changes. However, a systematic review in nanodevices for deep cartilage penetration is still lacking. Current approaches to assure penetration of nanosystems into the depth of cartilage were reviewed, including nanoscale extracellular vesicles from different cell lines and nanocarriers with appropriate balance in cationic property and size particle. Moreover, nanodevices entering clinical trials and further optimization were also discussed, providing important guiding significance to future research.


Assuntos
Cartilagem Articular , Nanotubos de Carbono , Ácidos Nucleicos , Osteoartrite , Adulto , Humanos , Osteoartrite/patologia , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Cátions , Proteínas/farmacologia
13.
J Control Release ; 350: 525-537, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36055597

RESUMO

To overcome drug resistance and improve precision theranostics for hepatocellular carcinoma (HCC), a nanoplatform with an "off/on" function for multimodality imaging (near-infrared-II (NIR-II) fluorescence imaging, magnetic resonance imaging (MRI), and photoacoustic imaging) and synergistic therapy (photodynamic therapy and ferroptosis) activated by an acidic pH in the tumor microenvironment is proposed. Although many photosensitizers with photodynamic effects have been reported, very few of them have outstanding photodynamic effect and high stability with response to endogenous stimuli capable of NIR-II imaging. Herein, a new amphiphilic photosensitizer SR780 derived from croconaine dye, was developed with satisfactory photodynamic effects and pH-responsive NIR-II imaging. Interestingly, it was deactivated by coordination with Fe3+ (SR780@Fe) and activated during their release under mild acidic condition. Ferroptosis can generate hydroxyl free radical and lipid peroxide, which aggravate the oxidative stress of tumor cells and mediate their death while depleting glutathione (GSH) to enhance photodynamic effect. In situ pH-activatable theranostic nanoplatform, SR780@Fe-PAE-GP, was thus developed by loading SR780@Fe with pH-responsive polymers, modified by a glypican-3 (GPC-3) receptor-targeting peptide. The synergistic antitumor effects were confirmed both in vitro and in vivo, and the tumor inhibition rate of the SR780@Fe-PAE-GP + L treatment group reached 98%.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Nanopartículas , Neoplasias , Fotoquimioterapia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Glutationa , Glipicanas/uso terapêutico , Humanos , Concentração de Íons de Hidrogênio , Peróxidos Lipídicos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/uso terapêutico , Nanomedicina Teranóstica/métodos , Microambiente Tumoral
14.
Ann Transl Med ; 10(14): 806, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35965833

RESUMO

Background and Objective: Ischemic cerebrovascular disease is one of the main diseases threatening human health and survival and is a commonly occurring disease in neurology. Due to its high disability rate, ischemic cerebrovascular disease is one of the most important diseases to be prevented and treated at present. The risk factors of cerebral ischemia include atherosclerosis, hypertension, hyperlipidemia, and blood viscosity caused by thrombocytosis. After cerebral ischemia, cerebral ischemia-reperfusion injury may be induced by oxidative stress (OS), inflammatory reaction, nitric oxide damage, apoptosis, excitatory amino acid toxicity, calcium (Ca2+) overload, and other mechanisms. Hesperidin is a flavanone compound and is a key component in citrus plants. It is a kind of traditional Chinese medicine extract with high levels of Pericarpium, shell, fruit, and green peel. In recent years, Hesperidin has received great attention, compelling evidence has indicated Hesperidin plays a beneficial role in cerebral ischemia. Methods: We conducted a literature search for published manuscripts hesperidin in ischemia/reperfusion up to December 2021 in common English databases (i.e., PubMed, EMBASE, Web of Science, SpringerLink, Wiley, Cochrane Library) and Chinese databases [Chinese BioMedical Literature Service System (CBM), WANFANG database, China Knowledge Resource Integrated Database (CNKI)]. Key Content and Findings: In this article, we reviewed the mechanisms of action of hesperidin in the treatment of cerebral ischemia, including antioxidant stress, anti-inflammatory reaction, anti-atherosclerosis, anti-thrombosis, anti-apoptosis, and nitric oxide regulation. Conclusions: In this narrative review, Hesperidin exhibits antioxidant stress, anti-platelet aggregation, vasodilation, anti-atherosclerotic, anti-inflammatory, anti-apoptotic, hypolipidemic, anti-tumor, cardiovascular protection, and nitric oxide-release regulatory properties Such a comprehension of the recent progress of hesperidin will help identify biomarkers for diagnosis and therapeutic targets to cerebral ischemia.

15.
Cell Discov ; 8(1): 80, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35973984

RESUMO

Severe eosinophilic asthma (SEA) is a therapy-resistant respiratory condition with poor clinical control. Treatment efficacy and patient compliance of current therapies remain unsatisfactory. Here, inspired by the remarkable success of chimeric antigen receptor-based cellular adoptive immunotherapies demonstrated for the treatment of a variety of malignant tumors, we engineered a cytokine-anchored chimeric antigen receptor T (CCAR-T) cell system using a chimeric IL-5-CD28-CD3ζ receptor to trigger T-cell-mediated killing of eosinophils that are elevated during severe asthma attacks. IL-5-anchored CCAR-T cells exhibited selective and effective killing capacity in vitro and restricted eosinophil differentiation with apparent protection against allergic airway inflammation in two mouse models of asthma. Notably, a single dose of IL-5-anchored CCAR-T cells resulted in persistent protection against asthma-related conditions over three months, significantly exceeding the typical therapeutic window of current mAb-based treatments in the clinics. This study presents a cell-based treatment strategy for SEA and could set the stage for a new era of precision therapies against a variety of intractable allergic diseases in the future.

16.
Transl Cancer Res ; 11(6): 1781-1794, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35836521

RESUMO

Background: Glioblastoma is the most common type of malignant tumor of the brain. Despite substantial improvements in therapy, the 5-year survival rate of patients with glioblastoma remains low. Antitumor drug development has encountered considerable obstacles, which can be attributed to metastasis and the blood-brain barrier (BBB). Hesperetin (HSP), derived from citrus fruits, exhibits several biological properties, including anticancer and anti-inflammatory activities. In addition, in vitro models have shown that HSP can easily cross the BBB. The purpose of the present study was to explore the effects and underlying mechanisms of HSP on glioblastoma cells. Methods: GL261 cell were cultured and treated with different dose HSP. The cell viability was assessed with Cell Counting Kit-8 (CCK-8) assay. The cell apoptosis was determined using an Annexin V/propidine iodide (PI) staining and Hoechst staining and detection assay, cell migration and invasion were observed on GL261 cells using Matrigel-coated Transwells and Wound-Healing assay. The expression of proteins was detected by Western blotting. Results: HSP suppressed cell proliferation and could induce apoptosis, the latter of which might be regulated through the Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor-kappa B (NF-κB) pathways. Furthermore, HSP inhibited cell migration and invasion by downregulating the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, and inhibited epithelial-mesenchymal transition (EMT) by upregulating the expression of E-cadherin while downregulating N-cadherin and vimentin expression. Conclusions: These findings suggest HSP to be an alternative preventive and therapeutic antiglioblastoma drug that may be especially useful for patients with recurrent glioblastoma.

17.
J Nanobiotechnology ; 20(1): 194, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35443712

RESUMO

As a natural product with various biological activities, triptolide (TP) has been reported in anti-inflammatory, anti-tumor and anti-autoimmune studies. However, the narrow therapeutic window, poor water solubility, and fast metabolism limit its wide clinical application. To reduce its adverse effects and enhance its efficacy, research and design of targeted drug delivery systems (TDDS) based on nanomaterials is one of the most viable strategies at present. This review summarizes the reports and studies of TDDS combined with TP in recent years, including passive and active targeting of drug delivery systems, and specific delivery system strategies such as polymeric micelles, solid lipid nanoparticles, liposomes, and stimulus-responsive polymer nanoparticles. The reviewed literature presented herein indicates that TDDS is a multifunctional and efficient method for the delivery of TP. In addition, the advantages and disadvantages of TDDS are sorted out, aiming to provide reference for the combination of traditional Chinese medicine and advanced nano drug delivery systems (NDDS) in the future.


Assuntos
Nanomedicina , Nanopartículas , Diterpenos , Portadores de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Compostos de Epóxi , Lipossomos , Medicina Tradicional Chinesa , Nanomedicina/métodos , Fenantrenos
18.
Theranostics ; 12(1): 76-86, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34987635

RESUMO

Background: Hepatocellular carcinoma (HCC) is associated with high morbidity and mortality rates. The development of novel nanomaterials represents an important direction for precise HCC theranostics. The combination of photothermal and sonodynamic therapy has provided great benefits for HCC therapy. Theranostic agents in the second near-infrared window (NIR-II, 1000-1700 nm) show great prospects because of their extraordinarily high detection sensitivity, resolution, and deep penetration. Methods: A sharp pH-sensitive self-assembling Glypican-3 (GPC3)-binding peptide (GBP) dye, CR-PEG-GBP, was developed as an intelligent nanoprobe for NIR-II imaging and photoacoustic (PA) imaging-guided photothermal therapy (PTT) and sonodynamic therapy (SDT) of HCC. Results: This small molecule assembled nanoprobe exhibited advantageous properties, such as responding to a decrease in pH (from normal tissue (pH 7.4) to the tumor microenvironment (pH ~6.5)) and aggregating - from small nanoprobes (<20 nm at pH 7.4) - into large nanoparticles (>160 nm at pH 6.5 and >510 nm at pH 5.5) that enables enhanced imaging and therapeutic effects. Because CR-PEG-GBP can self-aggregate in situ in an acidic tumor microenvironment, it shows high tumor accumulation and long tumor retention time, while being excretable from normal tissues and safe. Conclusions: This intelligent self-assembling small molecule strategy provides a simple yet efficient solution for HCC theranostics and may open up new avenues for designing clinically translatable probes for HCC treatment.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Animais , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Camundongos Nus
19.
Angew Chem Int Ed Engl ; 61(13): e202112925, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-34932846

RESUMO

Combination therapy based on different mechanisms of cell death has shown promise in tumor therapy. However, when different modalities are integrated, the maximum synergy of the therapeutic effects is often lacking in the design. Herein, we report a cancer theranostic nanomedicine formula developed by considering the mechanisms of action of ferroptosis and the photothermal effect in combination therapy. The croconaine molecule was encapsulated as both a photothermal converter and an iron-chelating agent with BSA, thus leading to biocompatible and stable Cro-Fe@BSA nanoparticles (NPs). The Cro-Fe@BSA NPs in the tumor milieu showed an activated photothermal effect leading to enhanced radical formation owing to the temperature-dependent Fenton reaction kinetics, while radical formation during ferroptosis in turn prevented the heat-induced formation of heat shock proteins and thus the self-protection mechanism of cancer cells in response to heat. The activatable photoacoustic and magnetic resonance imaging performance of the Cro-Fe@BSA NPs also enabled safe and reliable cancer theranostics.


Assuntos
Ferroptose , Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Linhagem Celular Tumoral , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Fototerapia , Medicina de Precisão , Nanomedicina Teranóstica
20.
J Nanobiotechnology ; 19(1): 387, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819084

RESUMO

Polydopamine (PDA), which is derived from marine mussels, has excellent potential in early diagnosis of diseases and targeted drug delivery owing to its good biocompatibility, biodegradability, and photothermal conversion. However, when used as a solid nanoparticle, the application of traditional PDA is restricted because of the low drug-loading and encapsulation efficiencies of hydrophobic drugs. Nevertheless, the emergence of mesoporous materials broaden our horizon. Mesoporous polydopamine (MPDA) has the characteristics of a porous structure, simple preparation process, low cost, high specific surface area, high light-to-heat conversion efficiency, and excellent biocompatibility, and therefore has gained considerable interest. This review provides an overview of the preparation methods and the latest applications of MPDA-based nanodrug delivery systems (chemotherapy combined with radiotherapy, photothermal therapy combined with chemotherapy, photothermal therapy combined with immunotherapy, photothermal therapy combined with photodynamic/chemodynamic therapy, and cancer theranostics). This review is expected to shed light on the multi-strategy antitumor therapy applications of MPDA-based nanodrug delivery systems.


Assuntos
Indóis , Sistemas de Liberação de Fármacos por Nanopartículas , Neoplasias , Terapia Fototérmica , Polímeros , Nanomedicina Teranóstica , Animais , Antineoplásicos , Linhagem Celular Tumoral , Humanos , Imunoterapia , Camundongos , Nanoestruturas , Neoplasias/diagnóstico , Neoplasias/terapia
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