Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 115
Filtrar
1.
Proc Natl Acad Sci U S A ; 120(1): e2214757120, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36574680

RESUMO

Cell membrane-coated nanoparticles are emerging as a new type of promising nanomaterials for immune evasion and targeted delivery. An underlying premise is that the unique biological functions of natural cell membranes can be conferred on the inherent physiochemical properties of nanoparticles by coating them with a cell membrane. However, the extent to which the membrane protein properties are preserved on these nanoparticles and the consequent bio-nano interactions are largely unexplored. Here, we synthesized two mesenchymal stem cell (MSC) membrane-coated silica nanoparticles (MCSNs), which have similar sizes but distinctly different stiffness values (MPa and GPa). Unexpectedly, a much lower macrophage uptake, but much higher cancer cell uptake, was found with the soft MCSNs compared with the stiff MCSNs. Intriguingly, we discovered that the soft MCSNs enabled the forming of a more protein-rich membrane coating and that coating had a high content of the MSC chemokine CXCR4 and MSC surface marker CD90. This led to the soft MCSNs enhancing cancer cell uptake mediated by the CD90/integrin receptor-mediated pathway and CXCR4/SDF-1 pathways. These findings provide a major step forward in our fundamental understanding of how the combination of nanoparticle elasticity and membrane coating may be used to facilitate bio-nano interactions and pave the way forward in the development of more effective cancer nanomedicines.


Assuntos
Nanopartículas , Neoplasias , Humanos , Membrana Celular/metabolismo , Nanopartículas/química , Proteínas/metabolismo , Neoplasias/metabolismo , Elasticidade
2.
Nano Lett ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38855905

RESUMO

Neurotoxins are known for their extreme lethality. However, due to their enormous diversity, effective and broad-spectrum countermeasures are lacking. This study presents a dual-modal cellular nanoparticle (CNP) formulation engineered for continuous neurotoxin neutralization. The formulation involves encapsulating the metabolic enzyme N-sulfotransferase (SxtN) into metal-organic framework (MOF) nanoparticle cores and coating them with a natural neuronal membrane, termed "Neuron-MOF/SxtN-NPs". The resulting nanoparticles combine membrane-enabled broad-spectrum neurotoxin neutralization with enzyme payload-enabled continuous neurotoxin neutralization. The studies confirm the protection of the enzyme payload by the MOF core and validate the continuous neutralization of saxitoxin (STX). In vivo studies conducted using a mouse model of STX intoxication reveal markedly improved survival rates compared with control groups. Furthermore, acute toxicity assessments show no adverse effects associated with the administration of Neuron-MOF/SxtN-NPs in healthy mice. Overall, Neuron-MOF/SxtN-NPs represent a unique biomimetic nanomedicine platform poised to effectively neutralize neurotoxins, marking an important advancement in the field of countermeasure nanomedicine.

3.
Small ; 20(14): e2309635, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37990378

RESUMO

Neurotoxins present a substantial threat to human health and security as they disrupt and damage the nervous system. Their potent and structurally diverse nature poses challenges in developing effective countermeasures. In this study, a unique nanoparticle design that combines dual-biomimicry mechanisms to enhance the detoxification efficacy of neurotoxins is introduced. Using saxitoxin (STX), one of the deadliest neurotoxins, and its natural binding protein saxiphilin (Sxph) as a model system, human neuronal membrane-coated and Sxph-loaded metal-organic framework (MOF) nanosponges (denoted "Neuron-MOF/Sxph-NS") are successfully developed. The resulting Neuron-MOF/Sxph-NS exhibit a biomimetic design that not only emulates host neurons for function-based detoxification through the neuronal membrane coating, but also mimics toxin-resistant organisms by encapsulating the Sxph protein within the nanoparticle core. The comprehensive in vitro assays, including cell osmotic swelling, calcium flux, and cytotoxicity assays, demonstrate the improved detoxification efficacy of Neuron-MOF/Sxph-NS. Furthermore, in mouse models of STX intoxication, the application of Neuron-MOF/Sxph-NS shows significant survival benefits in both therapeutic and prophylactic regimens, without any apparent acute toxicity. Overall, the development of Neuron-MOF/Sxph-NS represents an important advancement in neurotoxin detoxification, offering promising potential for treating injuries and diseases caused by neurotoxins and addressing the current limitations in neurotoxin countermeasures.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Animais , Camundongos , Humanos , Neurotoxinas , Membrana Celular , Proteínas de Transporte , Nanopartículas/química , Neurônios
4.
Small ; : e2401299, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38746996

RESUMO

The immunosuppressive tumor microenvironment (TME) reduces the chimeric antigen receptor (CAR) T-cell therapy against solid tumors. Here, a CAR T cell membrane-camouflaged nanocatalyst (ACSP@TCM) is prepared to augment CAR T cell therapy efficacy against solid tumors. ACSP@TCM is prepared by encapsulating core/shell Au/Cu2- xSe and 3-bromopyruvate with a CAR T cell membrane. It is demonstrated that the CAR T cell membrane camouflaging has much better-targeting effect than the homologous tumors cell membrane camouflaging. ACSP@TCM has an appealing synergistic chemodynamic/photothermal therapy (CDT/PTT) effect that can induce the immunogenic cell death (ICD) of NALM 6 cells. Moreover, 3-bromopyruvate can inhibit the efflux of lactic acid by inhibiting the glycolysis process, regulating the acidity of TME, and providing a more favorable environment for the survival of CAR T cells. In addition, the photoacoustic (PA) imaging and computed tomography (CT) imaging performance can guide the ACSP@TCM-mediated tumor therapy. The results demonstrated that the ACSP@TCM significantly enhanced the CAR T cell therapy efficacy against NALM 6 solid tumor mass, and completely eliminated tumors. This work provides an effective tumor strategy for CAR T cell therapy in solid tumors.

5.
Small ; 19(52): e2305551, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37635117

RESUMO

Nanoparticles coated with natural cell membranes have emerged as a promising class of biomimetic nanomedicine with significant clinical potential. Among them, macrophage membrane-coated nanoparticles hold particular appeal due to their versatility in drug delivery and biological neutralization applications. This study employs a genetic engineering approach to enhance their in vivo residence times, aiming to further improve their performance. Specifically, macrophages are engineered to express proline-alanine-serine (PAS) peptide chains, which provide additional protection against opsonization and phagocytosis. The resulting modified nanoparticles demonstrate prolonged residence times when administered intravenously or introduced intratracheally, surpassing those coated with the wild-type membrane. The longer residence times also contribute to enhanced nanoparticle efficacy in inhibiting inflammatory cytokines in mouse models of lipopolysaccharide-induced lung injury and sublethal endotoxemia, respectively. This study underscores the effectiveness of genetic modification in extending the in vivo residence times of macrophage membrane-coated nanoparticles. This approach can be readily extended to modify other cell membrane-coated nanoparticles toward more favorable biomedical applications.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas , Camundongos , Animais , Sistemas de Liberação de Medicamentos/métodos , Macrófagos/metabolismo , Membrana Celular/metabolismo , Citoplasma
6.
Nano Lett ; 22(1): 211-219, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-34967631

RESUMO

Human malaria is a global life-threatening infectious disease. Cerebral malaria (CM) induced by Plasmodium falciparum parasites accounts for 90% of malaria deaths. Treating CM is challenging due to inadequate treatment options and the development of drug resistance. We describe a nanoparticle formulation of the antimalarial drug dihydroartemisinin that is coated in a biomimetic membrane derived from brain microvascular endothelial cells (BMECs) and test its therapeutic efficacy in a mouse model of experimental cerebral malaria (ECM). The membrane-coated nanoparticle drug has a prolonged drug-release profile and enhanced dual targeting killing efficacy toward parasites residing in red blood cells (iRBCs) and iRBCs obstructed in the BMECs (for both rodent and human). In a mice ECM model, the nanodrug protects the brain, liver, and spleen from infection-induced damage and improves the survival rate of mice. This so-called nanodrug offers new insight into engineering nanoparticle-based therapeutics for malaria and other parasitic pathogen infections.


Assuntos
Antimaláricos , Malária Cerebral , Animais , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Encéfalo , Modelos Animais de Doenças , Células Endoteliais , Malária Cerebral/tratamento farmacológico , Camundongos , Plasmodium falciparum
7.
Nano Lett ; 22(23): 9672-9678, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36448694

RESUMO

Anthrax infections caused by Bacillus anthracis are an ongoing bioterrorism and livestock threat worldwide. Current approaches for management, including extended passive antibody transfusion, antibiotics, and prophylactic vaccination, are often cumbersome and associated with low patient compliance. Here, we report on the development of an adjuvanted nanotoxoid vaccine based on macrophage membrane-coated nanoparticles bound with anthrax toxins. This design leverages the natural binding interaction of protective antigen, a key anthrax toxin, with macrophages. In a murine model, a single low-dose vaccination with the nanotoxoids generates long-lasting immunity that protects against subsequent challenge with anthrax toxins. Overall, this work provides a new approach to address the ongoing threat of anthrax outbreaks and bioterrorism by taking advantage of an emerging biomimetic nanotechnology.


Assuntos
Vacinas contra Antraz , Antraz , Toxinas Bacterianas , Animais , Humanos , Camundongos , Antraz/prevenção & controle , Antígenos de Bactérias , Bacillus anthracis , Nanotecnologia
8.
Small ; 18(30): e2202337, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35780479

RESUMO

Osteosarcoma (OS) is one of the most common bone malignant tumors which mainly develops in adolescents. Although neoadjuvant chemotherapy has improved the prognosis of patients, numerous chemotherapeutic challenges still limit their use. Here, inspired by the Watson-Crick base pairing in nucleic acids, hydrophobic (methotrexate) and hydrophilic (floxuridine) chemo-drugs are mixed and self-assembled into M:F nanoparticles (M:F NPs) through molecular recognition. Then, the obtained NPs are co-extruded with membranes derived from OS cells to form cancer-cell membrane-coated NPs (CCNPs). With protected membranes at the outer layer, CCNPs are highly stable in both physiological and weak acid tumor conditions and possess homologous tumor targeted capability. Furthermore, the proteomic analysis first identifies over 400 proteins reserved in CCNPs, most of them participating in tumor cell targeting and adhesion processes. In vitro studies reveal that CCNPs significantly inhibit the PI3K/AKT/mTOR pathway, which promotes cell apoptosis and cell cycle arrest. More importantly, cell membrane camouflage significantly prolongs the circulation half-life of CCNPs, elevates the drug accumulation at tumor sites, and promotes anti-tumor efficacy in vivo. As a convenient and effective strategy to construct a biomimetic NP with high drug loading ratio, the CCNPs provide new potentials for precise and synergistic antitumor treatment.


Assuntos
Neoplasias Ósseas , Nanopartículas , Osteossarcoma , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , Membrana Celular , DNA , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Osteossarcoma/tratamento farmacológico , Fosfatidilinositol 3-Quinases , Proteômica
9.
Small ; 18(30): e2201933, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35789094

RESUMO

Selective induction of tumor thrombus infarction is a promising antitumor strategy. Non-persistent embolism due to non-compacted thrombus and activated fibrinolytic system within the tumor large blood vessels and tumor margin recurrence are the main therapeutic bottlenecks. Herein, an erythrocyte membrane-coated invisible acoustic-sensitive nanoparticle (TXA+DOX/PFH/RBCM@cRGD) is described, which can induce tumor thrombus infarction by precisely damaging tumor vascular endothelium. It is revealed that TXA+DOX/PFH/RBCM@cRGD can effectively accumulate on the endothelial surface of tumor vessels with the help of the red blood cell membrane (RBCM) stealth coating and RGD cyclic peptide (cRGD), which can be delivered in a targeted manner as nanoparticle missiles. As a kind of phase-change material, perfluorohexane (PFH) nanodroplets possess excellent acoustic responsiveness. Acoustic-sensitive missiles can undergo an acoustic phase transition and intense cavitation with response to low-intensity focused ultrasound (LIFU), damaging the tumor vascular endothelium, rapidly initiating the coagulation cascade, and forming thromboembolism in the tumor vessels. The drugs loaded in the inner water phase are released explosively. Tranexamic acid (TXA) inhibits the fibrinolytic system, and doxorubicin (DOX) eliminates the margin survival. In summary, a stealthy and acoustically responsive multifunctional nanoparticle delivery platform is successfully developed for inducing thrombus infarction by precisely damaging tumor vascular endothelium.


Assuntos
Nanopartículas , Neoplasias , Acústica , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Endotélio Vascular , Membrana Eritrocítica , Humanos , Infarto/tratamento farmacológico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico
10.
Small ; 18(3): e2104402, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34837321

RESUMO

Despite the activation of T lymphocytes by antigen-presenting cells being responsible for eliciting antigen-specific immune responses, their crosstalking suffers from temporospatial limitations and endogenous influencing factors, which restrict the generation of a strong antitumor immunity. Here, cascade cell membrane coating is reported to prepare biomimetic nanoparticles (BNs) that can manipulate the cross-priming of T cells. BNs are obtained from coating nanoparticulate substrates with cell membranes extracted from dendritic cells (DCs) that are pre-pulsed with cancer cell membrane-coated nanoparticles. With a DC membrane that presents an array of cancer cell membrane antigen epitopes, BNs inherit the intrinsic membrane function of DCs, which can directly cross-prime T cells and provoke robust yet antigen-specific antitumor responses in multiple mouse models. Combination with clinical anti-programmed death-1 antibodies demonstrates a robust way of BNs to achieve desirable tumor regression and survival rate. This work spotlights the impact of nanoparticles on direct cross-priming of T cells and supports a unique yet modulate platform for boosting an effective adaptive immunity for immunotherapy.


Assuntos
Vacinas Anticâncer , Nanopartículas , Animais , Apresentação de Antígeno , Biomimética , Membrana Celular , Apresentação Cruzada , Células Dendríticas/metabolismo , Camundongos , Linfócitos T
11.
Chemistry ; 28(68): e202200947, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36116117

RESUMO

Transmission electron microscopy (TEM) observations of negatively stained cell membrane (CM)-coated polymeric nanoparticles (NPs) reveal a characteristic core-shell structure. However, negative staining agents can create artifacts that complicate the determination of the actual NP structure. Herein, it is demonstrated with various bare polymeric core NPs, such as poly(lactic-co-glycolic acid) (PLGA), poly(ethylene glycol) methyl ether-block-PLGA, and poly(caprolactone), that certain observed core-shell structures are actually artifacts caused by the staining process. To address this issue, fluorescence quenching was applied to quantify the proportion of fully coated NPs and statistical TEM analysis was used to identify and differentiate whether the observed core-shell structures of CM-coated PLGA (CM-PLGA) NPs are due to artifacts or to the CM coating. Integrated shells in TEM images of negatively stained CM-PLGA NPs are identified as artifacts. The present results challenge current understanding of the structure of CM-coated polymeric NPs and encourage researchers to use the proposed characterization approach to avoid misinterpretations.


Assuntos
Membrana Celular
12.
J Nanobiotechnology ; 20(1): 538, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36544135

RESUMO

Nanoparticles have now long demonstrated capabilities that make them attractive to use in biology and medicine. Some of them, such as lipid nanoparticles (SARS-CoV-2 vaccines) or metallic nanoparticles (contrast agents) are already approved for their use in the clinic. However, considering the constantly growing body of different formulations and the huge research around nanomaterials the number of candidates reaching clinical trials or being commercialized is minimal. The reasons behind being related to the "synthetic" and "foreign" character of their surface. Typically, nanomaterials aiming to develop a function or deliver a cargo locally, fail by showing strong off-target accumulation and generation of adverse responses, which is connected to their strong recognition by immune phagocytes primarily. Therefore, rendering in negligible numbers of nanoparticles developing their intended function. While a wide range of coatings has been applied to avoid certain interactions with the surrounding milieu, the issues remained. Taking advantage of the natural cell membranes, in an approach that resembles a cell transfer, the use of cell-derived surfaces has risen as an alternative to artificial coatings or encapsulation methods. Biomimetic technologies are based on the use of isolated natural components to provide autologous properties to the nanoparticle or cargo being encapsulated, thus, improving their therapeutic behavior. The main goal is to replicate the (bio)-physical properties and functionalities of the source cell and tissue, not only providing a stealthy character to the core but also taking advantage of homotypic properties, that could prove relevant for targeted strategies. Such biomimetic formulations have the potential to overcome the main issues of approaches to provide specific features and identities synthetically. In this review, we provide insight into the challenges of nano-biointerfaces for drug delivery; and the main applications of biomimetic materials derived from specific cell types, focusing on the unique strengths of the fabrication of novel nanotherapeutics in cancer therapy.


Assuntos
Materiais Biomiméticos , COVID-19 , Nanopartículas , Neoplasias , Humanos , Biomimética , Vacinas contra COVID-19 , COVID-19/metabolismo , SARS-CoV-2 , Sistemas de Liberação de Medicamentos , Nanopartículas/uso terapêutico , Membrana Celular/metabolismo , Neoplasias/terapia , Neoplasias/metabolismo
13.
Nano Lett ; 21(6): 2603-2609, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33687220

RESUMO

Natural cell membranes derived from various cell sources have been successfully utilized to coat nanomaterials for functionalization. However, intracellular membranes from the organelles of eukaryotes remain unexplored. Herein, we choose mitochondrion as a representative cell organelle and coat outer mitochondrial membrane (OMM) from mouse livers onto nanoparticles and field-effect transistors (FETs) through a membrane vesicle-substrate fusion process. Polymeric nanoparticles coated with OMM (OMM-NPs) can bind with ABT-263, a B-cell lymphoma protein 2 (Bcl-2) inhibitor that targets the OMM. As a result, OMM-NPs effectively protect the cells from ABT-263 induced cell death and apoptosis in vitro and attenuated ABT-263-induced thrombocytopenia in vivo. Meanwhile, FET sensors coated with OMM (OMM-FETs) can detect and distinguish anti-Bcl-2 antibody and small molecule agonists. Overall, these results show that OMM can be coated onto the surfaces of both nanoparticles and functional devices, suggesting that intracellular membranes can be used as coating materials for novel biointerfacing.


Assuntos
Membranas Mitocondriais , Nanopartículas , Animais , Apoptose , Membrana Celular , Camundongos , Mitocôndrias , Membranas Mitocondriais/metabolismo
14.
Nano Lett ; 21(13): 5522-5531, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34133181

RESUMO

Cell-membrane-coated nanoparticles have emerged as a promising antitumor therapeutic strategy. However, the immunologic mechanism remains elusive, and there are still crucial issues to be addressed including tumor-homing capacity, immune incompatibility, and immunogenicity. Here, we reported a tumor-associated macrophage membrane (TAMM) derived from the primary tumor with unique antigen-homing affinity capacity and immune compatibility. TAMM could deplete the CSF1 secreted by tumor cells in the tumor microenvironment (TME), blocking the interaction between TAM and cancer cells. Especially, after coating TAMM to upconversion nanoparticle with conjugated photosensitizer (NPR@TAMM), NPR@TAMM-mediated photodynamic immunotherapy switched the activation of macrophages from an immunosuppressive M2-like phenotype to a more inflammatory M1-like state, induced immunogenic cell death, and consequently enhanced the antitumor immunity efficiency via activation of antigen-presenting cells to stimulate the production of tumor-specific effector T cells in metastatic tumors. This TAM-membrane-based photodynamic immunotherapy approach offers a new strategy for personalized tumor therapy.


Assuntos
Imunoterapia , Nanopartículas , Macrófagos , Fármacos Fotossensibilizantes/uso terapêutico , Microambiente Tumoral
15.
Angew Chem Int Ed Engl ; 61(24): e202203115, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35395111

RESUMO

Metal-organic-framework nanoparticles (MOF NPs) have been increasingly used to encapsulate therapeutic enzymes for delivery. To better interface these MOF NPs with biological systems, researchers have coated them with natural cell membranes, enabling biomimicking properties suitable for innovative biomedical applications. Herein, we report that the enzymatic activity of cell-membrane-coated MOF NPs can be significantly enhanced by reducing membrane cholesterol content. We demonstrate such cholesterol-enzymatic activity correlation using zeolitic imidazolate framework-8 MOF NPs to encapsulate catalase, horseradish peroxidase, and organophosphate hydrolase, respectively. MOF NPs coated with membranes of human red blood cells or macrophages show similar outcomes, illustrating the broad applicability of this finding. The mechanistic investigation further reveals that reducing cholesterol levels effectively enhances membrane permeability likely responsible for the increased enzymatic activity. These results also imply a facile approach to tailoring the enzymatic activity of cell-membrane-coated MOF NPs by simply tuning the membrane cholesterol level.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Zeolitas , Membrana Celular/metabolismo , Humanos , Estruturas Metalorgânicas/metabolismo
16.
Small ; 17(46): e2103645, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34668309

RESUMO

Nanozyme-based cascade reaction has emerged as an effective strategy for disease treatment because of its high efficiency and low side effects. Herein, a new and highly active two-dimensional Pd-Ru nanozyme is prepared and then integrated with uricase and red blood cell (RBC) membrane to fabricate a tandem nanoreactor, Pd-Ru/Uricase@RBC, for hyperuricemia treatment. The designed Pd-Ru/Uricase@RBC nanoreactor displayed not only good stability against extreme pH, temperature and proteolytic degradation, but also long circulation half-life and excellent safety. The nanoreactor can effectively degrade UA by uricase to allantoin and H2 O2 and remove H2 O2 by using Pd-Ru nanosheets (NSs) with the catalase (CAT)-like activity. More importantly, the finally produced O2 from H2 O2 decomposition can in turn facilitate the catalytic oxidation of UA, as the degradation of UA is an O2 consumption process. By integrating the high-efficiency enzymatic activity, long circulation capability, and good biocompatibility, the designed Pd-Ru/Uricase@RBC can effectively and safely treat hyperuricemia without side effects. The study affords a new alternative for the exploration of clinical treatment of hyperuricemia.


Assuntos
Hiperuricemia , Urato Oxidase , Membrana Celular , Humanos , Hiperuricemia/tratamento farmacológico , Nanotecnologia , Ácido Úrico
17.
Nano Lett ; 20(7): 5367-5375, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32515974

RESUMO

Geometry-matching has been known to benefit the formation of stable biological interactions in natural systems. Herein, we report that the spiky nanostructures with matched topography to the influenza A virus (IAV) virions could be used to design next-generation advanced virus inhibitors. We demonstrated that nanostructures with spikes between 5 and 10 nm bind significantly better to virions than smooth nanoparticles, due to the short spikes inserting into the gaps of glycoproteins of the IAV virion. Furthermore, an erythrocyte membrane (EM) was coated to target the IAV, and the obtained EM-coated nanostructures could efficiently prevent IAV virion binding to the cells and inhibit subsequent infection. In a postinfection study, the EM-coated nanostructures reduced >99.9% virus replication at the cellular nontoxic dosage. We predict that such a combination of geometry-matching topography and cellular membrane coating will also push forward the development of nanoinhibitors for other virus strains, including SARS-CoV-2.


Assuntos
Betacoronavirus/ultraestrutura , Infecções por Coronavirus/virologia , Nanoestruturas/ultraestrutura , Pneumonia Viral/virologia , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Sítios de Ligação , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Desenho de Fármacos , Humanos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/ultraestrutura , Microscopia Eletrônica , Modelos Biológicos , Nanotecnologia , Pandemias , Pneumonia Viral/tratamento farmacológico , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/ultraestrutura , Internalização do Vírus/efeitos dos fármacos
18.
Nano Lett ; 20(1): 11-21, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31858807

RESUMO

We herein propose a bioengineering approach where bacterial outer membrane vesicles (OMVs) were coated on drug-loaded polymeric micelles to generate an innovative nanomedicine for effective cancer immunotherapy and metastasis prevention. Whereas OMVs could activate the host immune response for cancer immunotherapy, the loaded drug within polymeric micelles would exert both chemotherapeutic and immunomodulatory roles to sensitize cancer cells to cytotoxic T lymphocytes (CTLs) and to kill cancer cells directly. We demonstrated that the systemic injection of such a bioinspired immunotherapeutic agent would not only provide effective protective immunity against melanoma occurrence but also significantly inhibited tumor growth in vivo and extended the survival rate of melanoma mice. Importantly, the nanomedicine could also effectively inhibit tumor metastasis to the lung. The bioinspired immunomodulatory nanomedicine we have developed repurposes the bacterial-based formulation for cancer immunotherapy, which also defines a useful bioengineering strategy to the improve current cancer immunotherapeutic agents and delivery systems.


Assuntos
Bactérias/química , Membrana Celular/química , Portadores de Fármacos , Imunoterapia , Melanoma Experimental , Nanomedicina , Animais , Bioengenharia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Humanos , Imunidade Celular/efeitos dos fármacos , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Melanoma Experimental/terapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Nano Lett ; 20(2): 936-946, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31671946

RESUMO

Despite rapid advancements in antitumor drug delivery, insufficient intracellular transport and subcellular drug accumulation are still issues to be addressed. Cancer cell membrane (CCM)-camouflaged nanoparticles (NPs) have shown promising potential in tumor therapy due to their immune escape and homotypic binding capacities. However, their efficacy is still limited due to inefficient tumor penetration and compromised intracellular transportation. Herein, a yolk-shell NP with a mesoporous silica nanoparticle (MSN)-supported PEGylated liposome yolk and CCM coating, CCM@LM, was developed for chemotherapy and exhibited a homologous tumor-targeting effect. The yolk-shell structure endowed CCM@LM with moderate rigidity, which might contribute to the frequent transformation into an ellipsoidal shape during infiltration, leading to facilitated penetration throughout multicellular spheroids in vitro (up to a 23.3-fold increase compared to the penetration of membrane vesicles). CCM@LM also exhibited a cellular invasion profile mimicking an enveloped virus invasion profile. CCM@LM was directly internalized by membrane fusion, and the PEGylated yolk (LM) was subsequently released into the cytosol, indicating the execution of an internalization pathway similar to that of an enveloped virus. The incoming PEGylated LM further underwent efficient trafficking throughout the cytoskeletal filament network, leading to enhanced perinuclear aggregation. Ultimately, CCM@LM, which co-encapsulated low-dose doxorubicin and the poly(ADP-ribose) polymerase inhibitor, mefuparib hydrochloride, exhibited a significantly stronger antitumor effect than the first-line chemotherapeutic drug Doxil. Our findings highlight that NPs that can undergo facilitated tumor penetration and robust intracellular trafficking have a promising future in cancer chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Antineoplásicos/química , Linhagem Celular Tumoral , Membrana Celular/química , Vesículas Revestidas/química , Doxorrubicina/análogos & derivados , Doxorrubicina/química , Doxorrubicina/farmacologia , Humanos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Dióxido de Silício/química , Esferoides Celulares/química
20.
Molecules ; 26(13)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34279401

RESUMO

The membrane is a crucial component of Zn slurry-air flow battery since it provides ionic conductivity between the electrodes while avoiding the mixing of the two compartments. Herein, six commercial membranes (Cellophane™ 350PØØ, Zirfon®, Fumatech® PBI, Celgard® 3501, 3401 and 5550) were first characterized in terms of electrolyte uptake, ion conductivity and zincate ion crossover, and tested in Zn slurry-air flow battery. The peak power density of the battery employing the membranes was found to depend on the in-situ cell resistance. Among them, the cell using Celgard® 3501 membrane, with in-situ area resistance of 2 Ω cm2 at room temperature displayed the highest peak power density (90 mW cm-2). However, due to the porous nature of most of these membranes, a significant crossover of zincate ions was observed. To address this issue, an ion-selective ionomer containing modified poly(phenylene oxide) (PPO) and N-spirocyclic quaternary ammonium monomer was coated on a Celgard® 3501 membrane and crosslinked via UV irradiation (PPO-3.45 + 3501). Moreover, commercial FAA-3 solutions (FAA, Fumatech) were coated for comparison purpose. The successful impregnation of the membrane with the anion-exchange polymers was confirmed by SEM, FTIR and Hg porosimetry. The PPO-3.45 + 3501 membrane exhibited 18 times lower zincate ions crossover compared to that of the pristine membrane (5.2 × 10-13 vs. 9.2 × 10-12 m2 s-1). With low zincate ions crossover and a peak power density of 66 mW cm-2, the prepared membrane is a suitable candidate for rechargeable Zn slurry-air flow batteries.

SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa