A66: Use of gemcitabine-loaded superparamagnetic iron oxide nanoparticles against pancreatic cancer cells in an artificial circulatory model.

Sumit Nandi1,Paul Sykes1,Erol Hasan1,Michael Barrow1,Eithne Costello1,Matthew Rosseinsky1,John Hunt1,Christopher Halloran1

1University of Liverpool, Liverpool, UK

Presenting date: Monday 2 November
Presenting time: 13.10-14.00

Background

Pancreatic cancer is a devastating malignancy. Survival rates have barely improved since the 1970s, despite advancement in chemotherapy and surgical treatments. Newer approaches to its treatment are desperately required. Nanotechnology can provide novel and targeted therapy for pancreatic cancer. Gemcitabine-loaded superparamagnetic iron oxide nanoparticles (G-SPIONs) have proven cytotoxic effect against static pancreatic cancer cell lines in vitro. Our aim is to determine: i) whether G-SPIONs can be removed from a dynamic artificial circulation by magnetic targeting and ii) whether they have a cytotoxic effect upon pancreatic cancer cell lines, in this model.

Method

Culture media (RPMI) was continuously circulated through two specifically manufactured 25cm2 flasks containing monolayers of 2x106 MiaPaCa-2 cells within a 37oC/5%CO2 incubator. Monolayers were subjected to control media or 2% rhodamine-labelled G-SPIONs, with/without a magnet under the flasks for 16/24/48/72 hours. Corresponding experiments were performed without flow of media (static). LDH assay was performed as a measure of cell lysis following treatment. Light and fluorescent microscopy was used to visualise the monolayer and G-SPIONs, respectively.

Results

Marked cell lysis occurred over areas of maximal magnetic field strength (MAG).

 

Time (hr)

No MAG (% lysis)

MAG (%)

16

4.79

32.05 (p<0.001)

24

8.77

34.07 (p<0.001)

48

69.47

73.21 (p=0.02)

72

67.12

70.18 (p=0.004)

 

 

Light microscopy confirmed destruction of monolayers, especially over MAG. Co-localisation fluorescent microscopy demonstrated uptake of G-SPIONs by cells with increased signal seen over areas of MAG.

Conclusion

G-SPIONs can successfully be drawn from circulation and destroy monolayers. The magnetic targeting mechanism has most effect at early time points and although has reducing effect, is still significant at 72 hours. Bio-magnetic targeting in custom-made nano-vehicles provides a potential novel theranostic solution to chemotherapy for pancreatic cancer.