Bacterial Protoplast-Derived Nanovesicles Carrying CRISPR/Cas9 Tools Efficiently Re-educate Tumor-Associated Macrophages for Cancer Immunotherapy
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE243428 | GEO | 2023/11/27
REPOSITORIES: GEO
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Project description:we developed an in vivo CRISPR-Cas9 genome editing system that targets tumor-associated macrophages (TAMs) via bacterial protoplast-derived nanovesicles (NVs) decorated with a pH-responsive PEG conjugated polymer and galactosamine-conjugated ligand
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Project description:Neurodegenerative diseases affect millions of people worldwide and the presence of various physiological barriers limits the accessibility to the brain and reduces the efficacy of various therapies. Moreover, improving the solubility, stability and release of the drug in specific brain regions and in particular target cells (neuron or microglia), are essential factor to develop an efficient and targeted therapy for the treatment of brain disorders. Extracellular vesicles, nanoparticles and artificial nanovesicles represent a promising tool for contrast brain diseases, thanks to their ability to deliver therapeutic molecules and overcoming the problems mentioned. In this study, for the first time, we generated artificial nanovesicles derived from brain tissue, which were preliminary evaluated as potential brain delivery system. The nanovesicles were produced from myelin extracted from the brain, called Myelin NanoVesicles (MyVes). MyVes produced have an average diameter of 100nm, negative zeta potential, spheroidal morphology, lipids and main proteins of the myelin sheath and exhibit good cytocompatibility. The MyVes, are able to load a drug/molecule and cross a blood brain barrier model, in addition, they targeted specific brain regions, white matter and are able to interact mainly with the microglia cell line. Therefore, we propose MyVes for white matter and microglia targeted delivery as a potential approach to counteract white matter microglia related diseases
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2022-12-07 | MSV000090860 | MassIVE
Project description:In this study, we particularly focused on microRNA cargo of nanovesicles in bronchoalveolar lavage of severe asthmatic patients when compared to healthy controls. We extracted nanovesicle RNA using a serial filtration method. RNA content was analyzed with small RNA sequencing and mapped to pathways affected using WebGestalt 2017 Software. We report that severe asthma patients have deficient loading of microRNAs into their airway luminal nanovesicles and an altered profile of small RNA nanovesicle content (i.e., ribosomal RNA and broken transcripts, etc.).
2020-07-11 | GSE152729 | GEO
Project description:Here, we engineered functional EV-like nanovesicles (NVs) from human-induced pluripotent stem cells and highlight their potential as a functional surrogate for natural EVs for tissue repair. Proteome profiling of target cells further identified pathways implicated in angiogenesis (MYH10, AAMP, SLC3A2), cell survival (CCN2, RHEB, IGF2R, MFGE8), and fibroblast activation (CCN2, STAT3, COL1A1/2/4A2/12A1, ACTN1/4, ACTC1). This study demonstrates scalable generation of functional NVs and highlights their potential as a functional surrogate for natural EVs for tissue repair.
2023-01-15 | PXD036654 | Pride
Project description:IntroductionMany childhood cancer survivors are disengaged from cancer-related follow-up care despite being at high risk of treatment-related late effects. Innovative models of long-term follow-up (LTFU) care to manage ongoing treatment-related complications are needed. 'Re-engage' is a nurse-led eHealth intervention designed to improve survivors' health-related self-efficacy, targeted at survivors disengaged from follow-up. Re-engage aims to overcome survivor- and parent-reported barriers to care and ensure survivors receive the care most appropriate to their risk level.Methods and analysisThis study will recruit 30 Australian childhood cancer survivors who are not receiving any cancer-related care. Participation involves two online/telephone consultations with a survivorship nurse for medical assessment, a case review, risk stratification and creation of a care plan by a multidisciplinary team of specialists. We will assess the feasibility of implementing 'Re-engage' and its acceptability to participants and health professionals involved. The primary outcome will be survivors' health-related self-efficacy, measured at baseline and 1 and 6?months postintervention. Secondary outcomes will include the effect of 'Re-engage' on survivors' health behaviours and beliefs, engagement in healthcare, information needs and emotional well-being. We will also document the cost per patient to deliver 'Re-engage'. If Re-engage is acceptable, feasible and demonstrates early efficacy, it may have the potential to empower survivors in coordinating their complex care, improving survivors' long-term engagement and satisfaction with care. Ideally, it will be implemented into clinical practice to recall survivors lost to follow-up and reduce the ongoing burden of treatment for childhood cancer.Ethics and disseminationThe study protocol has been approved by the South Eastern Sydney Local Health District Human Research Ethics Committee (reference number: 16/366). The results will be disseminated in peer-reviewed journals and at scientific conferences. A lay summary will be published on the Behavioural Sciences Unit website.Trial registration numberACTRN12618000194268.
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2007-09-01 | E-MEXP-1145 | biostudies-arrayexpress
Project description:BackgroundIn the present study, we aimed to investigate the influence of lactate shuttling on the functional polarization and spatial distribution of transitional cell carcinoma of the bladder (TCCB) cells and macrophages.MethodsWe designed a microfluidic coculture chip for real-time integrative assays. The effect of lactate shuttling on the re-education of macrophages by TCCB cells was explored by measuring the levels of NO using a total NO assay kit and by evaluating the protein expression of iNOS, p-NFkB-p65, Arg-1 and HIF-1? via cell immunofluorescence and western blotting. Additionally, we examined TCCB cell viability using acridine orange/ethidium bromide (AO/EB) and MitoTracker staining. Moreover, the concentration distributions of lactate and large signaling proteins in the culture chambers were measured using 4',6-diamidino-2-phenylindole (DAPI) and fluorescein isothiocyanate-dextran (FITC-dextran). Furthermore, the recruitment of macrophages and the influence of macrophages on BC metastasis were observed via light microscopy.ResultsWe confirmed that TCCB cells reprogrammed macrophages into an M2 phenotype. Moreover, lactate inhibited M1 polarization and induced M2 polarization of macrophages, but blockade of cancer cell-macrophage lactate flux significantly inhibited the re-education of macrophages by TCCB cells. In addition, lactate diffused faster and deeper than large signaling proteins in the microfluidic tumor microenvironment. Furthermore, lactate alone induced the migration of macrophages, and M1, but not M2, macrophages reduced the motility of TCCB cells.ConclusionsTCCB cells reprogrammed macrophages into an M2 phenotype in a manner that depended on cancer cell-TAM lactate flux. Furthermore, the lactate shuttle may be a determinant of the density of TAMs in tumor tissue.
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Project description:The ascending interest in human extracellular vesicles (EVs) has transferred only a little to plant derived EVs and nanovesicles yet. Although a series of investigations already pointed out promising health beneficial effects and drug delivery properties, adequate (pre)clinical studies are rare. This fact might be caused by the lack of sources with appropriate qualities. Our results demonstrate a new and well controllable source for plant EVs: plant cell suspension culture. In vitro cultured plant cells release EVs into the growth medium which could be harvested for pharmaceutical applications.
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