Abstract
We recently reported the fabrication of a novel polymer nanoparticle delivery system with simultaneously entrapped indocyanine green (ICG) and doxorubicin (DOX). This system has potential applications for combined chemotherapy and hyperthermia. Research in our group showed that simultaneous use of ICG and DOX with localized hyperthermia can produce the same effect as that achieved by larger doses of chemotherapy alone. In this study, we explored the potential of dual-agent PLGA nanoparticles (ICG-DOX-PLGANPs) to overcome multidrug resistance (MDR) mechanisms in cancer cells by increasing intracellular drug concentrations via nanoparticle uptake. ICG-DOX-PLGANPs were prepared by the O/W emulsion solvent evaporation method. The dominant processing parameters that control particle size and drug entrapment efficiencies of ICG and DOX were PLGA concentration, PVA concentration and initial drug content. We optimized our previous formulation based on those parameters. Entrapment efficiency of the optimized ICG-DOX-PLGANPs was measured by fluorescence measurements using the DMSO burst release procedure. The internalization of ICG–DOX–PLGANPs by three cancer cell lines was visualized by confocal laser microscopy and fluorescence microscopy. Cytotoxicity was assessed using the SRB assay. The nanoparticles produced by optimal formulation had sizes of 135±2 nm, (n=3) with a low poly-dispersity index (0.149±0.014, n=3) and a zeta potential of -11.67±1.8 mV. Drug loading was approximately 3% w/w for ICG and 4% w/w for DOX (n=3). Cellular uptake of ICG and DOX from ICG–DOX–PLGANPs in DOX-resistant MES-SA/Dx5 cancer cells was higher compared to free ICG and free DOX treatment. However, the same phenomenon was not observed in MES-SA and SKOV-3 cancer cell lines. The SRB cytotoxicity results show that ICG–DOX–PLGANPs are more toxic than free DOX in DOX-resistant cell lines.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Manchanda, R., Lei, T., Tang, Y., Fernandez-Fernandez, A., McGoron, A.J. (2010). Cellular Uptake and Cytotoxicity of a Novel ICG-DOX-PLGA Dual Agent Polymer Nanoparticle Delivery System. In: Herold, K.E., Vossoughi, J., Bentley, W.E. (eds) 26th Southern Biomedical Engineering Conference SBEC 2010, April 30 - May 2, 2010, College Park, Maryland, USA. IFMBE Proceedings, vol 32. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-14998-6_58
Download citation
DOI: https://doi.org/10.1007/978-3-642-14998-6_58
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-14997-9
Online ISBN: 978-3-642-14998-6
eBook Packages: EngineeringEngineering (R0)