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Issue 12, 2016
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Intracellular delivery of the PTEN protein using cationic lipidoids for cancer therapy

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Abstract

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor, mutated or inactive in a large percentage of human cancers. Restoring PTEN activity in cancer cells through gene therapy has shown to inhibit cell growth and induce apoptosis, particularly in cells with a PTEN deficiency. Gene therapy, however, comes with some inherent risks such as triggering an immune response and permanent off target effects. Nanoparticle assisted protein delivery could mitigate these liabilities while maintaining therapeutic integrity. In this report, we evaluated the use of cationic lipid-like (lipidoid) materials to intracellularly deliver the PTEN protein. We synthesized a small library of cationic lipidoid materials and screened for the delivery of PTEN based on cell viability. The lipidoid material EC16-80 was selected for high efficacy and the subsequent lipidoid–protein complex was characterized using DLS, zeta potential, and TEM. Intracellular delivery of PTEN with EC16-80 to the PTEN deficient prostate cancer cell line PC-3 resulted in a significant decrease in activated AKT and induced apoptosis. Interestingly, delivery of PTEN to PTEN deficient prostate cancer cell lines PC-3 and LNCaP compared to the breast cancer cell line, MCF-7 with endogenous PTEN, resulted in significantly lower IC50 values in PC-3 and LNCaP cells indicating that the treatment is predominantly specific to PTEN-deficient cells. Altogether, these results demonstrate the first intracellular delivery of recombinant PTEN using a synthetic delivery vehicle and highlight the potential of intracellular PTEN protein delivery as a potential targeted cancer therapy.

Graphical abstract: Intracellular delivery of the PTEN protein using cationic lipidoids for cancer therapy

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Publication details

The article was received on 23 Aug 2016, accepted on 30 Sep 2016 and first published on 17 Oct 2016


Article type: Paper
DOI: 10.1039/C6BM00580B
Citation: Biomater. Sci., 2016,4, 1773-1780
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    Intracellular delivery of the PTEN protein using cationic lipidoids for cancer therapy

    S. A. Altınoğlu, M. Wang, K. Q. Li, Y. Li and Q. Xu, Biomater. Sci., 2016, 4, 1773
    DOI: 10.1039/C6BM00580B

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