Cationic solid lipid nanoparticles (SLN) complexed with plasmid DNA enhance prostate cancer cells (PC-3) migration

Abstract

Nanotechnology applications in biomedicine have increased in recent decades, primarily as therapeutic agents, drugs, and gene delivery systems. Among the nanoparticles used in medicine, we highlight cationic solid lipid nanoparticles (SLN). Given their nontoxic properties, much research has focused on the beneficial effects of SLN for drug or gene delivery system. However, little attention has been paid to the adverse impacts of SLN on the cellular environment, particularly their influence on intracellular signaling pathways. In this work, we investigate the effects triggered by cationic SLN on human prostate non-tumor cells (PNT1A) and tumor cells (PC-3). Our results demonstrate that cationic SLN enhances the migration of PC-3 prostate cancer cells but not PNT1A non-tumor prostate cells, an unexpected and unprecedented development. Furthermore, we observed that the enhanced cell migration velocity is a concentration-dependent and nanoparticle-dependent effect, and not related to any individual nanoparticle component. Moreover, cationic SLN increased vimentin expression (p < 0.05) but SLN did not affect Smad2 nuclear translocation. Meanwhile, EMT-related (epithelial-to-mesenchymal transition) proteins, such as ZEB1, underwent nuclear translocation when treated with cationic SLN, thereby affecting PC-3 cell motility through ZEB1 and vimentin modulation. From a therapeutic perspective, cationic SLN could potentially worsen a patient’s condition if these results were reproduced in vivo. Understanding the in vitro molecular mechanisms triggered by nanomaterials and their implications for cell function is crucial for defining their safe and effective use.

Keywords:

• Epithelial-to-mesenchymal transition
• cell signaling
• scratch assay
• wound healing
• proliferation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Additional information

Funding

This study was financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001 [grant #88887.514583/2020-00, CAPES/PROEX Finance Code 001], São Paulo Research Foundation (FAPESP) [grants #2014/03002-7, 2019/24033-1, 2020/01218-3, 2022/01483-4], National Council for Scientific and Technological Development (CNPq), and Fund for Support to Teaching, Research and Outreach Activities – FAEPEX – UNICAMP [grants #2178/22, #2421/20].