A hollow mesoporous
silica nanoparticle (
HMSNP) based
drug/
siRNA co-delivery system was designed and fabricated, aiming at overcoming multidrug resistance (MDR) in
cancer cells for targeted
cancer therapy. The as-prepared HMSNPs have perpendicular nanochannels connecting to the internal hollow cores, thereby facilitating
drug loading and release. The extra volume of the hollow core enhances the
drug loading capacity by two folds as compared with conventional mesoporous
silica nanoparticles (MSNPs).
Folic acid conjugated
polyethyleneimine (PEI-FA) was coated on the
HMSNP surfaces under neutral conditions through electrostatic interactions between the partially charged amino groups of PEI-FA and the
phosphate groups on the
HMSNP surfaces, blocking the mesopores and preventing the loaded drugs from leakage.
Folic acid acts as the targeting
ligand that enables the co-delivery system to selectively bind with and enter into the target
cancer cells. PEI-FA-coated HMSNPs show enhanced
siRNA binding capability on account of electrostatic interactions between the amino groups of PEI-FA and
siRNA, as compared with that of MSNPs. The electrostatic interactions provide the feasibility of pH-controlled release. In vitro pH-responsive
drug/
siRNA co-delivery experiments were conducted on HeLa cell lines with high
folic acid receptor expression and MCF-7 cell lines with low
folic acid receptor expression for comparison, showing effective target delivery to the HeLa cells through
folic acid receptor meditated cellular endocytosis. The pH-responsive intracellular
drug/
siRNA release greatly minimizes the prerelease and possible side effects of the delivery system. By simultaneously delivering both
doxorubicin (Dox) and
siRNA against the Bcl-2
protein into the HeLa cells, the expression of the
anti-apoptotic protein Bcl-2 was successfully suppressed, leading to an enhanced therapeutic efficacy. Thus, the present multifunctional nanoparticles show promising potentials for controlled and targeted
drug and gene co-delivery in
cancer treatment.