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Camel milk extracellular vesicles-mediated co-delivery of siVEGF/sorafenib enhances the anti-hepatocellular carcinoma activity by dual-effect blocking the biological effects of VEGF.

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Title: Camel milk extracellular vesicles-mediated co-delivery of siVEGF/sorafenib enhances the anti-hepatocellular carcinoma activity by dual-effect blocking the biological effects of VEGF.
Authors: Chen, Feng1 (AUTHOR), Pan, Yichen1 (AUTHOR), Fang, Zhou1 (AUTHOR), Song, Mengdi1 (AUTHOR), Zhang, Wang1 (AUTHOR), Yuan, Hui1 (AUTHOR), Gao, Xinran1 (AUTHOR), Zhang, Min1,2,3 (AUTHOR) zhangmin@shou.edu.cn, Liu, Kehai1,2 (AUTHOR) khliu@shou.edu.cn
Source: Journal of Controlled Release. Sep2025, Vol. 385, pN.PAG-N.PAG. 1p.
Subjects: Treatment effectiveness, Extracellular vesicles, Drug delivery systems, Intravenous injections, Hepatocellular carcinoma
Abstract: In view of the combined effect of paracrine and autocrine of VEGF in tumor tissues, this study proposed to use sorafenib to block VEGF signaling pathway, while siRNA was used to interfere with tumor cell autocrine of VEGF, so as to achieve double-effect blocking of VEGF biological effects and further improve anti-tumor efficacy. Here, we constructed a novel co-delivery system (so -cEVs-PPT/siVEGF) based on camel milk-derived extracellular vesicles (cEVs) modified by Plannic 123-polyethylenimine-tLyP-1 transmembrane peptide polymer (PPT) for the delivery of siVEGF and sorafenib. The results showed that so -cEVs-PPT/siVEGF exhibited significant tumor inhibition and low side effects on hepatocellular carcinoma mice, and the combined administration system had stronger anti-tumor effects than siVEGF or sorafenib alone. More importantly, the two different delivery modes of intravenous injection and intratumoral injection showed comparable anti-tumor therapeutic effects, which proved that the drug delivery system had superior targeted therapeutic effects. This study proposes an innovative combination therapy strategy that provides new perspectives and possibilities for the treatment of hepatocellular carcinoma. [Display omitted] • A novel sorafenib/siVEGF co-delivery system based on camel milk extracellular vesicles (cEVs). • tLyP-1 tumor targeting peptide modified P123-PEI was grafted onto cEVs, by which efficient siRNA loading could be achieved. • The co-delivery system mediated by so-cEVs-PPT/siVEGF can enhance the anti-tumor effect, without causing systemic toxicity. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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DbLabel: Engineering Source
An: 187264149
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
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  Label: Title
  Group: Ti
  Data: Camel milk extracellular vesicles-mediated co-delivery of siVEGF/sorafenib enhances the anti-hepatocellular carcinoma activity by dual-effect blocking the biological effects of VEGF.
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  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Chen%2C+Feng%22">Chen, Feng</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pan%2C+Yichen%22">Pan, Yichen</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fang%2C+Zhou%22">Fang, Zhou</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Song%2C+Mengdi%22">Song, Mengdi</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Wang%22">Zhang, Wang</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yuan%2C+Hui%22">Yuan, Hui</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gao%2C+Xinran%22">Gao, Xinran</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Min%22">Zhang, Min</searchLink><relatesTo>1,2,3</relatesTo> (AUTHOR)<i> zhangmin@shou.edu.cn</i><br /><searchLink fieldCode="AR" term="%22Liu%2C+Kehai%22">Liu, Kehai</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<i> khliu@shou.edu.cn</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Controlled+Release%22">Journal of Controlled Release</searchLink>. Sep2025, Vol. 385, pN.PAG-N.PAG. 1p.
– Name: Subject
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  Data: <searchLink fieldCode="DE" term="%22Treatment+effectiveness%22">Treatment effectiveness</searchLink><br /><searchLink fieldCode="DE" term="%22Extracellular+vesicles%22">Extracellular vesicles</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+delivery+systems%22">Drug delivery systems</searchLink><br /><searchLink fieldCode="DE" term="%22Intravenous+injections%22">Intravenous injections</searchLink><br /><searchLink fieldCode="DE" term="%22Hepatocellular+carcinoma%22">Hepatocellular carcinoma</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: In view of the combined effect of paracrine and autocrine of VEGF in tumor tissues, this study proposed to use sorafenib to block VEGF signaling pathway, while siRNA was used to interfere with tumor cell autocrine of VEGF, so as to achieve double-effect blocking of VEGF biological effects and further improve anti-tumor efficacy. Here, we constructed a novel co-delivery system (so -cEVs-PPT/siVEGF) based on camel milk-derived extracellular vesicles (cEVs) modified by Plannic 123-polyethylenimine-tLyP-1 transmembrane peptide polymer (PPT) for the delivery of siVEGF and sorafenib. The results showed that so -cEVs-PPT/siVEGF exhibited significant tumor inhibition and low side effects on hepatocellular carcinoma mice, and the combined administration system had stronger anti-tumor effects than siVEGF or sorafenib alone. More importantly, the two different delivery modes of intravenous injection and intratumoral injection showed comparable anti-tumor therapeutic effects, which proved that the drug delivery system had superior targeted therapeutic effects. This study proposes an innovative combination therapy strategy that provides new perspectives and possibilities for the treatment of hepatocellular carcinoma. [Display omitted] • A novel sorafenib/siVEGF co-delivery system based on camel milk extracellular vesicles (cEVs). • tLyP-1 tumor targeting peptide modified P123-PEI was grafted onto cEVs, by which efficient siRNA loading could be achieved. • The co-delivery system mediated by so-cEVs-PPT/siVEGF can enhance the anti-tumor effect, without causing systemic toxicity. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1016/j.jconrel.2025.113980
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      – Code: eng
        Text: English
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      Pagination:
        PageCount: 1
        StartPage: N.PAG
    Subjects:
      – SubjectFull: Treatment effectiveness
        Type: general
      – SubjectFull: Extracellular vesicles
        Type: general
      – SubjectFull: Drug delivery systems
        Type: general
      – SubjectFull: Intravenous injections
        Type: general
      – SubjectFull: Hepatocellular carcinoma
        Type: general
    Titles:
      – TitleFull: Camel milk extracellular vesicles-mediated co-delivery of siVEGF/sorafenib enhances the anti-hepatocellular carcinoma activity by dual-effect blocking the biological effects of VEGF.
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            NameFull: Chen, Feng
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            NameFull: Pan, Yichen
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            – D: 10
              M: 09
              Text: Sep2025
              Type: published
              Y: 2025
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