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Bioreducible Poly(Amino Ethers) Based mTOR siRNA Delivery for Lung Cancer

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A Correction to this article was published on 05 September 2018

This article has been updated

Abstract

Purpose

Lung cancer is one of the leading causes of deaths in the United States, but currently available therapies for lung cancer are associated with reduced efficacy and adverse side effects. Small interfering RNA (siRNA) can knock down the expression of specific genes and result in therapeutic efficacy in lung cancer. Recently, mTOR siRNA has been shown to induce apoptosis in NSCLC cell lines but its use is limited due to poor stability in biological conditions.

Methods

In this study, we modified an aminoglyocisde-derived cationic poly (amino-ether) by introducing a thiol group using Traut’s reagent to generate a bio-reducible modified–poly (amino-ether) (mPAE). The mPAE polymer was used to encapsulate mTOR siRNA by nanoprecipitation method, resulting in the formation of stable and bio-reducible nanoparticles (NPs) which possessed an average diameter of 114 nm and a surface charge of approximately +27 mV.

Results

The mTOR siRNA showed increased release from the mTS-mPAE NPs in the presence of 10 mM glutathione (GSH). The polymeric mTS-mPAE-NPs were also capable of efficient gene knockdown (60 and 64%) in A549 and H460 lung cancer cells, respectively without significant cytotoxicity at 30 μg/ml concentrations. The NPs also showed time-dependent cellular uptake for up to 24 h as determined using flow cytometry. Delivery of the siRNA using these NPs also resulted in significant inhibition of A549 and H460 cell proliferation in vitro, respectively.

Conclusions

The results demonstrate that the mPAE polymer based NPs show strong potential for siRNA delivery to lung cancer cells. It is anticipated that future modification can help improve the efficacy of nucleic acid delivery, leading to higher inhibition of lung cancer growth in vitro and in vivo.

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Change history

  • 05 September 2018

    Under the heading “Methods-Synthesis of the Bioreducible Modified-PAE (mPAE)”, on page 3, line 14–17, there is an error. The quantity unit of PAE and 2-iminothiolane hydrochloride needs to be corrected to mg instead of g.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, The Daniel K Inouye College of pharmacy, University of Hawaii at Hilo, Hilo, HI, 96720, USA

    Nishant S. Gandhi, Dana-Lynn T. Koomoa-Lange & Mahavir B. Chougule

  2. Translational Bio-pharma Engineering Nanodelivery Research Laboratory, Department of Pharmaceutics and Drug Delivery, School of Pharmacy, Faser Hall, University of Mississippi, University, MS, 38677, USA

    Nishant S. Gandhi & Mahavir B. Chougule

  3. Chemical Engineering, Arizona State University, Tempe, AZ, 85287-6106, USA

    Sudhakar Godeshala, Bhavani Miryala & Kaushal Rege

  4. Pii Center for Pharmaceutical Technology, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS, 38677, USA

    Mahavir B. Chougule

  5. National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS, 38677, USA

    Mahavir B. Chougule

Authors
  1. Nishant S. Gandhi
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  2. Sudhakar Godeshala
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  3. Dana-Lynn T. Koomoa-Lange
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  4. Bhavani Miryala
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  5. Kaushal Rege
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  6. Mahavir B. Chougule
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Corresponding author

Correspondence to Mahavir B. Chougule.

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Gandhi, N.S., Godeshala, S., Koomoa-Lange, DL.T. et al. Bioreducible Poly(Amino Ethers) Based mTOR siRNA Delivery for Lung Cancer. Pharm Res 35, 188 (2018). https://doi.org/10.1007/s11095-018-2460-z

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  • DOI: https://doi.org/10.1007/s11095-018-2460-z

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