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
Affiliations
Tianxin Miao
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
Andrew C. Little
Cellular, Molecular and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT 05405, USA
Alexander Aronshtam
Department of Medicine, Stem Cell Core, Larner College of Medicine, University of Vermont, Colchester, VT 05446, USA
Taylor Marquis
Department of Medicine, Stem Cell Core, Larner College of Medicine, University of Vermont, Colchester, VT 05446, USA
Spencer L. Fenn
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
Milena Hristova
Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA
Dimitry N. Krementsov
Department of Biomedical and Health Sciences, College of Nursing and Health Sciences, University of Vermont, Burlington, VT 05405, USA
Albert van der Vliet
Cellular, Molecular and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT 05405, USA
Jeffrey L. Spees
Cellular, Molecular and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT 05405, USA
Rachael A. Oldinski
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
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.
