In order to achieve
superior delivery of the anticancer drug gemcitabine
to Mia PaCa-2 pancreatic cancer cell lines, we have synthesized transferrin
(Tf)-conjugated, polymer-coated, mesoporous silica nanoparticles (MSNs),
with optimization of multiple parameters. The following challenges
were thereby addressed to improve the efficacy of gemcitabine delivery:
(i) optimization of internal pore diameter (within the range 2.5–5.2
nm) and amine functionalization of MSN (NH2-MSN) to improve
drug loading and its controlled release, (ii) coating of MSN with
pH-sensitive polymers such as either chitosan or poly(d,l-lactide-co-glycolide) (PLGA), so as to prevent
premature release of the drug at physiological pH 7.4 and to also
achieve its controlled release at a lower pH 5.5 (extracellular cancer
cell pH), and finally, (iii) conjugation of Tf ligand on this optimized,
polymer-coated MSN, for better uptake of MSN by the MIA PaCa-2 cells,
through ligand–receptor interactions. Consequently, the highest
drug loading of 27.2% could be achieved for the sample having amine-functionalized
MSN with larger pore diameter of 5.2 nm, compared to only 13.1% for
small pore diameter of 2.5 nm, demonstrating better drug loading with
larger pores. Furthermore, with coating of PLGA on MSN, a more controlled
and desirable constant release
rate of gemcitabine with time was achieved at pH 5.5, compared to
a miniscule 3% of undesirable drug release at physiological pH 7.4.
Finally, for Tf-conjugated, polymer-coated MSN, 70–75% of MIA
PaCa-2 cells killing was achieved, as compared to 60% without Tf conjugation.
This was due to improved uptake of nanoparticles by cancer cells,
via ligand–receptor interactions. Thus, the above-optimized
MSN-based gemcitabine delivery system can be a superior formulation
to contain pancreatic cancer cell growth.