Development of Mesoporous Silica Nanoparticles of Tunable Pore Diameter for Superior Gemcitabine Drug Delivery in Pancreatic Cancer Cells.

Abstract

Superior delivery of anticancer drug gemcitabine has been achieved with mesoporous silica nanoparticles (MSN), by addressing three challenges in MSN synthesis: (i) MSN was synthesized with particle diameter between 42 to 64 nm, to utilize enhanced permeability and retention effect of small particles, (ii) MSN of larger internal pore diameter (2.5-5.2 nm) was made as a tunable morphological parameter to optimize both drug loading and its release rate, in a controlled, differential manner and (iii) higher drug release at extracellular cancer-cell pH (5.5) was achieved, compared to physiological pH (7.4) of healthy cells. MSN with above features was made by the sol-gel route, with trimethylmethoxysilane as a size-quencher and hexane or decane as a pore expander. Highest gemcitabine loading of 14.92% and a cumulative release of 58% at pH 5.5 could be obtained with the optimum sample having pore diameter of 5.2 nm, in comparison to the desirably low 22% release at pH 7.4. Consequently, we obtained 60% cell growth-inhibition of pancreatic cancer cell-line (MIA Paca-2), via gemcitabine loaded MSN. This was possible because of increased gemcitabine release from MSN with larger pore diameter of 5.2 nm, simultaneously demonstrating good target-selectivity of MSN as a drug-carrier, due to engineering of its pore-size.