Microvesicle-mediated delivery of transforming growth factor β1 siRNA for the suppression of tumor growth in mice

Zhang, Yaqin; Liu, Limin; Yu, Junchuan; Zhu, Dunru; Zhang, Yujing; Li, Xi-Han; Gu, Hang; Zhang, Chenyu; Zen, Ke

doi:10.1016/j.biomaterials.2014.02.003

Cited by 97 publications

(72 citation statements)

References 37 publications

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“…These cell-derived small particles are also used as a safe vehicle for the delivery of targeted drugs, as well as miRNAs and siRNAs34353637. Exosomes have been known to mediate the immune escape, drug resistance and angiogenesis of tumours73839.…”

Section: Discussionmentioning

confidence: 99%

Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis

et al. 2017

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The metastatic organotropism has been one of the cancer's greatest mysteries since the ‘seed and soil' hypothesis. Although the role of EGFR in cancer cells is well studied, the effects of secreted EGFR transported by exosomes are less understood. Here we show that EGFR in exosomes secreted from gastric cancer cells can be delivered into the liver and is integrated on the plasma membrane of liver stromal cells. The translocated EGFR is proved to effectively activate hepatocyte growth factor (HGF) by suppressing miR-26a/b expression. Moreover, the upregulated paracrine HGF, which binds the c-MET receptor on the migrated cancer cells, provides fertile ‘soil' for the ‘seed', facilitating the landing and proliferation of metastatic cancer cells. Thus, we propose that EGFR-containing exosomes derived from cancer cells could favour the development of a liver-like microenvironment promoting liver-specific metastasis.

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Section: Discussionmentioning

confidence: 99%

Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis

et al. 2017

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“…They can also be used for antibody evasion, as two recent studies have shown that two pathogens, hepatitis A virus (9) and hepatitis C (10), can exploit EVs to hide from patient-derived antibodies against the virus. Furthermore, they are being engineered as therapeutic delivery vehicles for nucleic acids and drugs (11, 12). …”

Section: Introductionmentioning

confidence: 99%

Naturally enveloped AAV vectors for shielding neutralizing antibodies and robust gene delivery in vivo

et al. 2014

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Recently adeno-associated virus (AAV) became the first clinically approved gene therapy product in the western world. To develop AAV for future clinical application in a widespread patient base, particularly in therapies which require intravenous (i.v.) administration of vector, the virus must be able to evade pre-existing antibodies to the wild type virus. Here we demonstrate that in mice, AAV vectors associated with extracellular vesicles (EVs) can evade human anti-AAV neutralizing antibodies. We observed different antibody evasion and gene transfer abilities with populations of EVs isolated by different centrifugal forces. EV-associated AAV vector (ev-AAV) was up to 136-fold more resistant over a range of neutralizing antibody concentrations relative to standard AAV vector in vitro. Importantly in mice, at a concentration of passively transferred human antibodies which decreased i.v. administered standard AAV transduction of brain by 80%, transduction of ev-AAV transduction was not reduced and was 4,000-fold higher. Finally, we show that expressing a brain targeting peptide on the EV surface allowed significant enhancement of transduction compared to untargeted ev-AAV. Using ev-AAV represents an effective, clinically relevant approach to evade human neutralizing anti-AAV antibodies after systemic administration of vector.

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“…In many recent studies, intravenous injections have been frequently applied to deliver siRNAs to major organs, including the kidney, liver, heart and lung [39,40] with a delivery efficiency of 30-40% [41]. In this study, we used lung cancer cell-xenograft mice by inoculating two NSCLC cell lines (A549 and H460) to evaluate siRNA-mediated silencing in vivo.…”

Section: Discussionmentioning

confidence: 99%

Suppression of tumor growth in lung cancer xenograft model mice by poly(sorbitol-co-PEI)-mediated delivery of osteopontin siRNA

Cho

Hong

Singh

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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Microvesicle-mediated delivery of transforming growth factor β1 siRNA for the suppression of tumor growth in mice

Cited by 97 publications

References 37 publications

Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis

Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis

Naturally enveloped AAV vectors for shielding neutralizing antibodies and robust gene delivery in vivo

Suppression of tumor growth in lung cancer xenograft model mice by poly(sorbitol-co-PEI)-mediated delivery of osteopontin siRNA

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