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Anti-GPC3 Antibody Tagged Cationic Switchable Lipid-Based Nanoparticles for the Co-Delivery of Anti-miRNA27a And Sorafenib in Liver Cancers

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Abstract

Purpose

The immediate plasma metabolism and development of chemo-resistance (single agent) severely hampers the clinical effectiveness of Sorafenib (SRF) in liver cancer therapy. MicroRNA27a inhibition is a promising biological strategy for breast cancer therapy.

Methods

In this study, we aimed to prepare SRF and anti-miRNA27a-loaded anti-GPC3 antibody targeted lipid nanoparticles to enhance the therapeutic efficacy against liver cancers. In this study, we have employed a unique cationic switchable lipid (CSL) as a mean to encapsulate miRNA as well as to confer pH-responsiveness to the nanocarrier system.

Results

The G-S27LN was nanosized and offered a pH-responsive release of SRF from the carrier system and we have demonstrated the specific affinity of G-S27LN towards the GPC3-overexpressed HepG2 cancer cells. Anti-microRNA27a significantly increased the protein expression of FOXO1 and PPAR-γ which are crucial components involved in proliferation and apoptosis of tumor cells. Combination of SRF and anti-miRNA27a (G-S27LN) resulted in significantly lower cell viability with a marked increase in the apoptosis cell proportion compared to that of free SRF indicating the synergistic anticancer effect. Animal studies in liver cancer xenograft model demonstrated significant suppression of tumor burden, reduced tumor cell and elevated TUNEL positive apoptosis with no toxicity concerns in animals treated with G-S27LN formulation.

Conclusion

The CSL-based G-S27LN efficiently co-delivered anti-microRNA27a and SRF and therefore represents a promising therapy to treat liver cancer. This study also brings forth a platform strategy for the effective treatment of number of other advanced cancers.

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Abbreviations

CSL:

Cationic switchable lipid

G-S27LN:

Anti-GPC3 antibody-linked SRF/anti-miR27a-loaded lipid nanoparticles

HCC:

Hepatocellular carcinoma

MiRNA:

Micro RNA

S27LN:

SRF/anti-miR27a-loaded lipid nanoparticles

SRF:

Sorafenib

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ACKNOWLEDGMENTS AND DISCLOSURES

This study was supported by Youth Fund from the First Affiliated Hospital of Zhengzhou University.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Zhengfeng Wang, Kun Zhao, Yingxuan Zhang, Xinxin Duan & Yongfu Zhao

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  1. Zhengfeng Wang
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  2. Kun Zhao
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  3. Yingxuan Zhang
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  4. Xinxin Duan
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  5. Yongfu Zhao
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Correspondence to Zhengfeng Wang.

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Wang, Z., Zhao, K., Zhang, Y. et al. Anti-GPC3 Antibody Tagged Cationic Switchable Lipid-Based Nanoparticles for the Co-Delivery of Anti-miRNA27a And Sorafenib in Liver Cancers. Pharm Res 36, 145 (2019). https://doi.org/10.1007/s11095-019-2669-5

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