Targeted delivery of a novel anticancer compound anisomelic acid using chitosan-coated porous silica nanorods for enhancing the apoptotic effect

Abstract

Targeted delivery of a novel anticancer compound anisomelic acid using chitosan-coated porous silica nanorods for enhancing the apoptotic effect, 2015, BIOMATERIALS SCIENCE, (3) 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 bioavailabil ity, 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 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 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.

Shape engineering boosts antibacterial activity of chitosan coated mesoporous silica nanoparticle doped with silver: a mechanistic investigation

“…29 The size distributions of MSPs were obtained by performing detail statistical analysis of TEM images for MSP1, MSP2 and MSP4 samples as presented in Fig. 1.…”

Nanoscale Materials in Targeted Drug Delivery

“…Poly(dimethylaminoethyl methacrylate)-poly(butylmethacrylate) polymeric micelles transfected COS-7 and OVCAR-3 cells efficiently with minor toxicity (Funhoff et al 2005). Folate-targeted chitosan NPs intracellular delivery was more target specific than non targeted ones (Senthilkumar et al 2015). In another Karmali et al (2009) study, folate-conjugated chitosan NPs showed greater cytotoxicity and uptake in folate receptor expressing cells (Song et al 2013).…”

On the intracellular release mechanism of hydrophobic cargo and its relation to the biodegradation behavior of mesoporous silica nanocarriers

“…(Li and Huang, 2008) We have to date shown that our developed MSN platform can be functionalized for cancer cell specific internalization and is suitable for targeted delivery of hydrophobic compounds including commercially available anticancer drugs, (Mamaeva et al, 2011; A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 5 Niemelä et al, 2015;Senthilkumar et al, 2015;Wittig et al, 2014) for which the release of cargo has been mainly confined to the intracellular environment. (Lu et al, 2007) In vivo we have shown that the carrier can be intravenously, locally and orally administered, accumulates in tumor tissue, lacks cytotoxic side-effects, is biodegradable and most likely eliminated through renal excretion after intravenous administration.…”

“…Our nanocarrier system has already previously been comprehensively evaluated for cytotoxicity, proven non-cytotoxic and biocompatible, (Desai et al, 2016;Mamaeva et al, 2011;Rosenholm et al, 2009a;Senthilkumar et al, 2015;Wittig et al, 2014) and was thus A C C E P T E D M A N U S C R I P T…”