Internalized FGF-2-Loaded Nanoparticles Increase Nuclear ERK1/2 Content and Result in Lung Cancer Cell Death

Tianxin Miao; Andrew C Little; Alexander Aronshtam; Taylor Marquis; Spencer L Fenn; Milena Hristova; Dimitry N Krementsov; Albert van der Vliet; Jeffrey L Spees; Rachael A Oldinski

doi:10.3390/nano10040612

Internalized FGF-2-Loaded Nanoparticles Increase Nuclear ERK1/2 Content and Result in Lung Cancer Cell Death

Nanomaterials (Basel). 2020 Mar 27;10(4):612. doi: 10.3390/nano10040612.

Authors

Tianxin Miao¹, Andrew C Little^{2

3}, Alexander Aronshtam⁴, Taylor Marquis⁴, Spencer L Fenn¹, Milena Hristova³, Dimitry N Krementsov⁵, Albert van der Vliet^{2

3}, Jeffrey L Spees^{2

4}, Rachael A Oldinski^{1

6

7

8}

Affiliations

¹ Bioengineering Program, College of Engineering and Mathematical Sciences, Larner College of Medicine, College of Engineering and Mathematical Sciences, University of Vermont, Burlington VT 05405, USA.
² Cellular, Molecular and Biomedical Sciences Graduate Program, University of Vermont, Burlington, Vermont 05405, USA.
³ Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, VT 05405, USA.
⁴ Department of Medicine, Stem Cell Core, Larner College of Medicine, University of Vermont, Colchester, VT 05446, USA.
⁵ Department of Biomedical and Health Sciences, College of Nursing and Health Sciences, University of Vermont, Burlington, Vermont 05405, USA.
⁶ Department of Mechanical Engineering, College of Engineering and Mathematical Sciences, University of Vermont, Burlington, VT 05405, USA.
⁷ Department of Electrical and Biomedical Engineering, College of Engineering and Mathematical Sciences, University of Vermont, Burlington, VT 05405, USA.
⁸ Materials Science Program, College of Engineering and Mathematical Sciences, University of Vermont, Burlington, VT 05405, USA.

Abstract

: Innovative cancer treatments, which improve adjuvant therapy and reduce adverse events, are desperately needed. Nanoparticles provide controlled intracellular biomolecule delivery in the absence of activating external cell surface receptors. Prior reports suggest that intracrine signaling, following overexpression of basic fibroblast growth factor (FGF-2) after viral transduction, has a toxic effect on diseased cells. Herein, the research goals were to 1) encapsulate recombinant FGF-2 within stable, alginate-based nanoparticles (ABNs) for non-specific cellular uptake, and 2) determine the effects of ABN-mediated intracellular delivery of FGF-2 on cancer cell proliferation/survival. In culture, human alveolar adenocarcinoma basal epithelial cell line (A549s) and immortalized human bronchial epithelial cell line (HBE1s) internalized ABNs through non-selective endocytosis. Compared to A549s exposed to empty (i.e., blank) ABNs, the intracellular delivery of FGF-2 via ABNs significantly increased the levels of lactate dehydrogenase, indicating that FGF-2-ABN treatment decreased the transformed cell integrity. Noticeably, the nontransformed cells were not significantly affected by FGF-2-loaded ABN treatment. Furthermore, FGF-2-loaded ABNs significantly increased nuclear levels of activated-extracellular signal-regulated kinase ½ (ERK1/2) in A549s but had no significant effect on HBE1 nuclear ERK1/2 expression. Our novel intracellular delivery method of FGF-2 via nanoparticles resulted in increased cancer cell death via increased nuclear ERK1/2 activation.

Keywords: ERK1/2; cancer cell death; intracellular FGF-2; lung cancer; nanoparticles.

Abstract

Grants and funding