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CXCR4-targeted lipid-coated PLGA nanoparticles deliver sorafenib and overcome acquired drug resistance in liver cancer.

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Title: CXCR4-targeted lipid-coated PLGA nanoparticles deliver sorafenib and overcome acquired drug resistance in liver cancer.
Authors: Gao, Dong-Yu1, Lin, Ts-Ting1, Sung, Yun-Chieh1, Liu, Ya Chi1, Chiang, Wen-Hsuan2, Chang, Chih-Chun1, Liu, Jia-Yu1, Chen, Yunching1 yunching@mx.nthu.edu.tw
Source: Biomaterials. Oct2015, Vol. 67, p194-203. 10p.
Subjects: Liver cancer, Drug resistance in cancer cells, Cancer invasiveness, Lipid analysis, Nanomedicine, Macrophages
Abstract: Sorafenib, a multikinase inhibitor, has been used as an anti-angiogenic agent against highly vascular hepatocellular carcinoma (HCC) – yet associated with only moderate therapeutic effect and the high incidence of HCC recurrence. We have shown intratumoral hypoxia induced by sorafenib activated C-X-C receptor type 4 (CXCR4)/stromal-derived factor 1α (SDF1α) axis, resulting in polarization toward a tumor-promoting microenvironment and resistance to anti-angiogenic therapy in HCC. Herein, we formulated sorafenib in CXCR4-targeted lipid-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with a CXCR4 antagonist, AMD3100 to systemically deliver sorafenib into HCC and sensitize HCC to sorafenib treatment. We demonstrated that CXCR4-targeted NPs efficiently delivered sorafenib into HCCs and human umbilical vein endothelial cells (HUVECs) to achieve cytotoxicity and anti-angiogenic effect in vitro and in vivo . Despite the increased expression of SDF1α upon the persistent hypoxia induced by sorafenib-loaded CXCR4-targeted NPs, AMD3100 attached to the NPs can block CXCR4/SDF1α, leading to the reduced infiltration of tumor-associated macrophages, enhanced anti-angiogenic effect, a delay in tumor progression and increased overall survival in the orthotopic HCC model compared with other control groups. In conclusion, our results highlight the clinical potential of CXCR4-targeted NPs for delivering sorafenib and overcoming acquired drug resistance in liver cancer. [ABSTRACT FROM AUTHOR]
Copyright of Biomaterials 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.)
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  Data: CXCR4-targeted lipid-coated PLGA nanoparticles deliver sorafenib and overcome acquired drug resistance in liver cancer.
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  Data: <searchLink fieldCode="AR" term="%22Gao%2C+Dong-Yu%22">Gao, Dong-Yu</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Lin%2C+Ts-Ting%22">Lin, Ts-Ting</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Sung%2C+Yun-Chieh%22">Sung, Yun-Chieh</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Liu%2C+Ya+Chi%22">Liu, Ya Chi</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Chiang%2C+Wen-Hsuan%22">Chiang, Wen-Hsuan</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Chang%2C+Chih-Chun%22">Chang, Chih-Chun</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Liu%2C+Jia-Yu%22">Liu, Jia-Yu</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Chen%2C+Yunching%22">Chen, Yunching</searchLink><relatesTo>1</relatesTo><i> yunching@mx.nthu.edu.tw</i>
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  Data: <searchLink fieldCode="JN" term="%22Biomaterials%22">Biomaterials</searchLink>. Oct2015, Vol. 67, p194-203. 10p.
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  Data: <searchLink fieldCode="DE" term="%22Liver+cancer%22">Liver cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+resistance+in+cancer+cells%22">Drug resistance in cancer cells</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+invasiveness%22">Cancer invasiveness</searchLink><br /><searchLink fieldCode="DE" term="%22Lipid+analysis%22">Lipid analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Nanomedicine%22">Nanomedicine</searchLink><br /><searchLink fieldCode="DE" term="%22Macrophages%22">Macrophages</searchLink>
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  Data: Sorafenib, a multikinase inhibitor, has been used as an anti-angiogenic agent against highly vascular hepatocellular carcinoma (HCC) – yet associated with only moderate therapeutic effect and the high incidence of HCC recurrence. We have shown intratumoral hypoxia induced by sorafenib activated C-X-C receptor type 4 (CXCR4)/stromal-derived factor 1α (SDF1α) axis, resulting in polarization toward a tumor-promoting microenvironment and resistance to anti-angiogenic therapy in HCC. Herein, we formulated sorafenib in CXCR4-targeted lipid-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with a CXCR4 antagonist, AMD3100 to systemically deliver sorafenib into HCC and sensitize HCC to sorafenib treatment. We demonstrated that CXCR4-targeted NPs efficiently delivered sorafenib into HCCs and human umbilical vein endothelial cells (HUVECs) to achieve cytotoxicity and anti-angiogenic effect in vitro and in vivo . Despite the increased expression of SDF1α upon the persistent hypoxia induced by sorafenib-loaded CXCR4-targeted NPs, AMD3100 attached to the NPs can block CXCR4/SDF1α, leading to the reduced infiltration of tumor-associated macrophages, enhanced anti-angiogenic effect, a delay in tumor progression and increased overall survival in the orthotopic HCC model compared with other control groups. In conclusion, our results highlight the clinical potential of CXCR4-targeted NPs for delivering sorafenib and overcoming acquired drug resistance in liver cancer. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Biomaterials 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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        Value: 10.1016/j.biomaterials.2015.07.035
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        Text: English
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      – SubjectFull: Liver cancer
        Type: general
      – SubjectFull: Drug resistance in cancer cells
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      – SubjectFull: Cancer invasiveness
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      – SubjectFull: Lipid analysis
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      – SubjectFull: Nanomedicine
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      – SubjectFull: Macrophages
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      – TitleFull: CXCR4-targeted lipid-coated PLGA nanoparticles deliver sorafenib and overcome acquired drug resistance in liver cancer.
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              Text: Oct2015
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