In Vitro Delivery of Docetaxel to Cancer Cells by Hybrid PLGA@Organosilica Nanoparticles with Redox-Sensitive Molecular Gates

P. Botella, M. Quesada, V. Vicente, A. Cabrera, K. Fabregat
Instituto de Tecnologia Química (UPV-CSIC), ES

Keywords: cancer treatment, drug delivery, hybrid nanoparticles, PLGA-silica, redox-sensitive

Summary:

We have developed a novel hybrid material based in spherical PLGA nanoparticles containing hydrophobic molecules which have been covered by a thin layer (6-10 nm) of a redox-responsive amorphous organosilica shell. The outer layer incorporates a number of disulfide bonds working as chemical doors that can be selectively cleaved by intracellular reducing compounds (e.g., glutathione), leading to disassembly of the silica wall. Herein, we present the in vitro evaluation in HeLa cervix cancer cell line of this novel hybrid organic-inorganic nanoplatform loaded with docetaxel (PLGA-DTX@SiOS). Cells were incubated during 24 h with nanoparticles containing 0.0001-1 g L-1 in DTX equivalents. Cytotoxicity was evaluated by MTT assay, determining the IC50 values and comparing with the free drug and DTX-free particles. Results indicate that PLGA-DTX@SiOS induces cell death at lower concentration than the free drug. This is due to the extremely low solubility of DTX in aqueous medium, which complicates its availability in the cell culture. Conversely, DTX-free hybrid nanoparticles showed no effect over cell morphology and proliferation rate. These novel nanomedicines imposed a better control and slower release of encapsulated drug than bare PLGA nanoparticles, improving also cytotoxicity and availability of free DTX in in vitro studies.