Calcium phosphate-polymer hybrid nanoparticles for enhanced triple negative breast cancer treatment via co-delivery of paclitaxel and miR-221/222 inhibitors

In this study, a development of a novel calcium phosphate-polymer hybrid nanoparticle system is reported. The nanoparticle system can co-encapsulate and co-deliver a combination of therapeutic agents with different physicochemical properties (i.e., inhibitors for microRNA-221 and microRNA-222 (miRi-221/222) and paclitaxel (pac)). miRi-221/222 are hydrophilic and were encapsulated with calcium phosphate by co-precipitation in a water-in-oil emulsion. The precipitates were then coated with an anionic lipid, dioleoylphosphatidic acid (DOPA), to co-encapsulate hydrophobic paclitaxel outside the hydrophilic precipitates and inside the same nanoparticle. The nanoparticles formed by following this approach had a size of about <= 100 nm and contained both lipid-coated calcium phosphate/miRi and paclitaxel. This nanoparticle system was found to simultaneously deliver paclitaxel and miRi-221/222 to their intracellular targets, leading to inhibit proliferative mechanisms of miR-221/222 and thus significantly enhancing the therapeutic efficacy of paclitaxel. (C) 2016 Elsevier Inc. All rights reserved.