Calcium Phosphorus Nanoparticles Coloaded with Paclitaxel and ADAM-10-siRNA for the Treatment of Triple Negative Breast Cancer

Abstract

It is urgent to develop nonside effects and targeting and effective therapeutic agents for triple negative breast cancer (TNBC). Herein, first-line chemotherapeutic drug paclitaxel (PTX) and a disintegrin and metalloproteinase 10 (ADAM10) small interfering RNA (siRNA) were simultaneously encapsulated in shell-core-distinct nanoparticles to enhance tumor suppressive effect. Specifically, copolymer DSPE-PEG2K packed with PTX to form the hydrophobic core, while CaP shell coating siADAM10 to form the hydrophilic shell. The PEG chains in the outer layer of the nanoparticles prevent the immune system from engulfing them and thus increase their systemic circulation time. CaP-PTX/siADAM10 NPs could target tumor site through the enhanced permeability and retention (EPR) effect. The siADAM10 in outer shell is first released to exert its gene inhibitory effect to increase the sensitivity of tumor cells to chemotherapeutic drugs, and then, the inner PTX is released from the CaP-PTX/siADAM10 NPs to exert its tumor-killing effect. The codelivery system of chemotherapeutic agent and siRNA in a core-shell nanoparticle provided a potent effective cancer therapy.