Targeted delivery of a novel anticancer compound anisomelic acid using chitosan-coated porous silica nanorods for enhancing the apoptotic effect
2014
Senthilkumar, Rajendran | Karaman, Didem Şen | Paul, Preethy | Björk, Emma M. | Odén, Magnus | Eriksson, John E. | Rosenholm, Jessica M.
Targeted cancer therapies are currently a strong focus in biomedical research. The most common approach is to use nanocarrier-based targeting to specifically deliver conventional anticancer drugs to enhance their therapeutic efficacy, increase bioavailability, and decrease the side-effects on normal cells. A step further towards higher specificity and efficacy would be to employ specific novel drugs along with specific nanocarrier-based targeting. Our recent studies have demonstrated that a plant-derived diterpenoid compound, anisomelic acid (AA), induces apoptosis in cervical cancer cells. In this work, we describe the development of a folic acid (FA)-targeted AA delivery system using chitosan-coated rod-shaped mesoporous silica particles (Chitosan-NR-MSP). The cellular internalization and uptake enhancement of the FA-Chitosan-NR-MSP towards cancerous folate receptor (FR)-positive (SiHa and HeLa) and/or normal FR-negative (HEK 293) cells were assessed, which indicated that the intracellular uptake of FA-conjugated Chitosan-NR-MSP was more target-specific. Furthermore, the induction of apoptosis by AA-loaded chitosan-coated rod-shaped particles on SiHa cells was studied. By employing caspase-3 activation and PARP cleavage as measure of apoptosis, the FA-particle mediated AA treatment was clearly more effective, significantly enhancing apoptosis in comparison to non-targeted Chitosan-NR-MSP or free AA in SiHa cells, suggesting that the FA-Chitosan-NR-MSPs can be potentially utilized as a drug delivery system for cervical cancer treatment.
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