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miR-542-3p Appended Sorafenib/All-trans Retinoic Acid (ATRA)-Loaded Lipid Nanoparticles to Enhance the Anticancer Efficacy in Gastric Cancers

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Abstract

Purpose

In this study, miR-542-3p appended SRF/ATRA-loaded solid lipid nanoparticle was successfully prepared and demonstrated for its therapeutic efficacy against gastric cancers.

Methods

The particles were nanosized and typically spherical in shape. In vitro release study showed that release of ATRA was significantly slower compared to that of SRF from the NPs.

Results

MTT assay showed that miR-542-3p have a strong inhibitory effect on the proliferation of MGC-803 cancer cells in a typical dose dependent manner. Nanocarrier encapsulation of SRF + ATRA induced a significantly higher cytotoxic effect compared to either individual drug or cocktail combinations indicating that the cellular uptake of different formulations was rate limiting factor in the therapeutic efficacy. Importantly, miR-542-3p-based miSRNP exhibited an extremely significant toxic effect compared to any other treated group. Importantly, miSRNP induced a significantly higher early (~55%) and late (~15%) apoptotic effect in gastric cancer cells. In vivo anticancer analysis results clearly suggest that nanoparticle encapsulation of combination of SRF and miRNA (with miRNA) will have greater antitumor efficacy in tumor mice.

Conclusion

Overall, unique combination of miRNA coupled with SRF + ATRA in a lipid nanocarrier could be a promising therapeutic approach in gastric cancer treatment.

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Abbreviations

AEG-1:

Astrocyte-elevated gene-1

ATRA:

All-trans retinoic acid

EPR:

Enhanced permeation and retention

PEG:

Polyethylene glycol

SRF:

Sorafenib

SLN:

Solid lipid nanoparticles

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Acknowledgments and Disclosures

The work is funded from the research grant of Huazhong University of Science and Technology, China.

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Author notes

  1. Tong Li and Yu Zhang are contribute to this work equally.

Authors and Affiliations

  1. Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, 430022, China

    Tong Li

  2. Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, 430022, China

    Yu Zhang, Yuan-Pu Meng, Li-Shan Bo & Wen-Bo Ke

Authors
  1. Tong Li
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  2. Yu Zhang
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  3. Yuan-Pu Meng
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  4. Li-Shan Bo
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Corresponding author

Correspondence to Wen-Bo Ke.

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Li, T., Zhang, Y., Meng, YP. et al. miR-542-3p Appended Sorafenib/All-trans Retinoic Acid (ATRA)-Loaded Lipid Nanoparticles to Enhance the Anticancer Efficacy in Gastric Cancers. Pharm Res 34, 2710–2719 (2017). https://doi.org/10.1007/s11095-017-2202-7

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  • DOI: https://doi.org/10.1007/s11095-017-2202-7

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