Simultaneous Delivery of siRNA and Paclitaxel via a “Two-in-One” Micelleplex Promotes Synergistic Tumor Suppression

TLDR: Clear evidence is shown that the micelleplex is capable of delivering siRNA and paclitaxel simultaneously to the same tumoral cells both in vitro and in vivo and can induce a synergistic tumor suppression effect in the MDA-MB-435s xenograft murine model.

Abstract: Combination of two or more therapeutic strategies with different mechanisms can cooperatively prohibit cancer development. Combination of chemotherapy and small interfering RNA (siRNA)-based therapy represents an example of this approach. Hypothesizing that the chemotherapeutic drug and the siRNA should be simultaneously delivered to the same tumoral cell to exert their synergistic effect, the development of delivery systems that can efficiently encapsulate two drugs and successfully deliver payloads to targeted sites via systemic administration has proven to be challenging. Here, we demonstrate an innovative “two-in-one” micelleplex approach based on micellar nanoparticles of a biodegradable triblock copolymer poly(ethylene glycol)-b-poly(e-caprolactone)-b-poly(2-aminoethyl ethylene phosphate) to systemically deliver the siRNA and chemotherapeutic drug. We show clear evidence that the micelleplex is capable of delivering siRNA and paclitaxel simultaneously to the same tumoral cells both in vitro and in v...