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

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Innovative cancer therapies are needed to enhance adjuvant therapy and minimize adverse events.
• Nanoparticles offer controlled intracellular delivery of biomolecules, bypassing the need for cell surface receptor activation.
• Overexpression of basic fibroblast growth factor (FGF-2) via viral transduction has shown toxic effects on diseased cells through intracrine signaling.

Purpose of the Study:

• To encapsulate recombinant FGF-2 into stable alginate-based nanoparticles (ABNs) for non-specific cellular uptake.
• To evaluate the impact of ABN-mediated intracellular FGF-2 delivery on cancer cell proliferation and survival.

Main Methods:

• Alginate-based nanoparticles (ABNs) were formulated to encapsulate recombinant FGF-2.
• Human alveolar adenocarcinoma basal epithelial cells (A549s) and immortalized human bronchial epithelial cells (HBE1s) were cultured.
• Cells internalized ABNs via non-selective endocytosis.
• Lactate dehydrogenase levels and nuclear ERK1/2 activation were measured to assess cell viability and signaling pathways.

Main Results:

• A549 cells treated with FGF-2-loaded ABNs showed significantly increased lactate dehydrogenase levels, indicating compromised cell integrity.
• Nontransformed HBE1 cells were not significantly affected by FGF-2-loaded ABN treatment.
• FGF-2-loaded ABNs significantly increased nuclear levels of activated-extracellular signal-regulated kinase ½ (ERK1/2) in A549 cells but not in HBE1 cells.

Conclusions:

• This study presents a novel method for intracellular delivery of FGF-2 using nanoparticles.
• ABN-mediated delivery of FGF-2 selectively induces cancer cell death through enhanced nuclear ERK1/2 activation.
• This approach holds promise for developing targeted cancer therapies with reduced side effects.