Mitochondrial Surface Engineering for Multidrug Resistance Reversal

Multidrug resistance (MDR) is still a formidable obstacle for the majority of anticancer drugs during chemotherapy. MDR is generally divided into the pump and nonpump resistances, which significantly and simultaneously reduce drug accumulation and potency in various cancer cells. In order to concurrently combat the two pathways to completely overcome MDR, a novel siRNA-containing nanomaterial-coated mitochondria complex was developed, which can overcome the barrier of activity loss and electrostatic repulsion to effectively deliver siRNA and mitochondria into the MDR cells. In this way, the functional siRNA could successfully down-regulate pump resistance-related proteins while the transplanted mitochondria efficaciously played its role to improve apoptotic signal activation and transmissions by means of restoring intracellular metabolism environment. We believe this unique organelle-material complex would hold great promise to reverse overall MDR as a result of high spatial-temporal synchronization of potent synthetic and living species.