Extracellular vesicles in the breast cancer brain metastasis: physiological functions and clinical applications

Sakamoto, Yuima; Ochiya, Takahiro; Yoshioka, Yusuke

doi:10.3389/fnhum.2023.1278501

Cited by 5 publications

(2 citation statements)

References 122 publications

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“…One possibility is to use naturally derived particles with lipid membranes to deliver therapeutics across the BBB or improve delivery across the BTB. Extracellular vesicles (EVs) are small particles naturally released from cells that carry and deliver bioactive molecules as a method of cell-to-cell communication, and EVs from various types of cells have been shown to target tumors and cross the BBB. , EVs can be classified by mechanism of biogenesis, size, function, or composition; examples of EVs classified by biogenesis include exosomes, microvesicles, and apoptotic bodies . Exosomes are formed by internal budding within a multivesicular body and range in size from 40 to 150 nm in diameter.…”

Section: Introductionmentioning

confidence: 99%

“…Because of the overlapping size range of microvesicles and exosomes, EVs are often characterized as enriched populations of small EVs and large EVs rather than pure populations . Because EVs can circulate in the bloodstream for a prolonged period of time, can cross the BBB, ,,− and can be manipulated as carriers of drugs, nucleic acids, or nanoparticles, − there is vast potential to engineer EVs as imaging or delivery tools to target brain metastases. Previous studies have labeled EVs with superparamagnetic iron oxide (SPIO) nanoparticles for in vivo tracking using magnetic resonance imaging (MRI) − ,, and to a lesser extent, magnetic particle imaging (MPI) .…”

Section: Introductionmentioning

confidence: 99%

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Magnetic Particle Imaging Reveals that Iron-Labeled Extracellular Vesicles Accumulate in Brains of Mice with Metastases

Toomajian,

Tundo,

Ural

et al. 2024

ACS Appl. Mater. Interfaces

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Magnetic Particle Imaging Reveals that Iron-Labeled Extracellular Vesicles Accumulate in Brains of Mice with Metastases

Toomajian,

Tundo,

Ural

et al. 2024

ACS Appl. Mater. Interfaces

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Magnetic particle imaging reveals that iron-labeled extracellular vesicles accumulate in brains of mice with metastases

Toomajian,

Tundo,

Ural

et al. 2024

Preprint

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The incidence of breast cancer remains high worldwide and is associated with a significant risk of metastasis to the brain that can be fatal; this is due, in part, to the inability of therapeutics to cross the blood brain barrier (BBB). Extracellular vesicles (EVs) have been found to cross the BBB and further, have been used to deliver drugs to tumors. EVs from different cell types appear to have different patterns of accumulation and retention as well as efficiency of bioactive cargo delivery to recipient cells in the body. Engineering EVs as delivery tools to treat brain metastases, therefore, will require an understanding of the timing of EV accumulation, and their localization relative to metastatic sites. Magnetic particle imaging (MPI) is a sensitive and quantitative imaging method that directly detects superparamagnetic iron. Here, we demonstrate MPI as a novel tool to characterize EV biodistribution in metastatic disease after labeling EVs with superparamagnetic iron oxide (SPIO) nanoparticles. Iron-labeled EVs (FeEVs) were collected from iron-labeled parental primary 4T1 tumor cells and brain-seeking 4T1BR5 cells, followed by injection into mice with orthotopic tumors or brain metastases. MPI quantification revealed that FeEVs were retained for longer in orthotopic mammary carcinomas compared to SPIOs. MPI signal due to iron could only be detected in brains of mice bearing brain metastases after injection of FeEVs, but not SPIOs, or FeEVs when mice did not have brain metastases. These findings indicate the potential use of EVs as a therapeutic delivery tool in primary and metastatic tumors.

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The concept of natural genome reconstruction. Part 1. Basic provisions of the “natural genome reconstruction” concept. Changing the genome of hematopoietic stem cells using several natural cellular mechanisms that are inherent in the hematopoietic cell and determine its biological status as “the source of the body’s reparative potential”

Yakubov,

Taranov,

Sidorov

et al. 2024

Vestn. VOGiS

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We present a series of articles proving the existence of a previously unknown mechanism of interaction between hematopoietic stem cells and extracellular double-stranded DNA (and, in particular, double-stranded DNA of the peripheral bloodstream), which explains the possibility of emergence and fixation of genetic information contained in double-stranded DNA of extracellular origin in hematopoietic stem cells. The concept of the possibility of stochastic or targeted changes in the genome of hematopoietic stem cells is formulated based on the discovery of new, previously unknown biological properties of poorly differentiated hematopoietic precursors. The main provisions of the concept are as follows. The hematopoietic stem cell takes up and internalizes fragments of extracellular double-stranded DNA via a natural mechanism. Specific groups of glycocalyx factors, including glycoproteins/proteoglycans, glycosylphosphatidylinositol-anchored proteins and scavenger receptors, take part in the internalization event. The binding sites for DNA fragments are heparin-binding domains and clusters of positively charged amino acid residues that are parts of protein molecules of these factors. Extracellular fragments delivered to the internal compartments of hematopoietic stem cells initiate terminal differentiation, colony formation, and proliferation of hematopoietic precursors. The molecular manifestation of these processes is the emergence and repair of pangenomic single-strand breaks. The occurrence of pangenomic single-strand breaks and restoration of genome (genomic DNA) integrity are associated with activation of a “recombinogenic situation” in the cell; during its active phase, stochastic homologous recombination or other recombination events between extracellular fragments localized in the nucleus and chromosomal DNA are possible. As a result, genetic material of initially extracellular localization either integrates into the recipient genome with the replacement of homologous chromosomal segments, or is transitively present in the nucleus and can manifest itself as a new genetic trait. It is assumed that as a result of stochastic acts of homologous exchange, chromosome loci are corrected in hematopoietic stem cells that have acquired mutations during the existence of the organism, which are the cause of clonal hematopoiesis associated with old age. In this regard, there is a fundamental possibility of changing the hematopoietic status of hematopoietic stem cells in the direction of polyclonality and the original diversity of clones. Such events can form the basis for the rejuvenation of the blood-forming cell system. The results of the laboratory’s work indicate that other stem cells in the body capture extracellular DNA fragments too. This fact creates a paradigm for the overall rejuvenation of the body.

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Extracellular vesicles in the breast cancer brain metastasis: physiological functions and clinical applications

Cited by 5 publications

References 122 publications

Magnetic Particle Imaging Reveals that Iron-Labeled Extracellular Vesicles Accumulate in Brains of Mice with Metastases

Magnetic Particle Imaging Reveals that Iron-Labeled Extracellular Vesicles Accumulate in Brains of Mice with Metastases

Magnetic particle imaging reveals that iron-labeled extracellular vesicles accumulate in brains of mice with metastases

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