Innovative Delivery of siRNA to Solid Tumors by Super Carbonate Apatite

<div><p>RNA interference (RNAi) technology is currently being tested in clinical trials for a limited number of diseases. However, systemic delivery of small interfering RNA (siRNA) to solid tumors has not yet been achieved in clinics. Here, we introduce an <i>in vivo</i> pH-sensitive delivery system for siRNA using super carbonate apatite (sCA) nanoparticles, which is the smallest class of nanocarrier. These carriers consist simply of inorganic ions and accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Intravenously administered sCA-siRNA abundantly accumulated in the cytoplasm of tumor cells at 4 h, indicating quick achievement of endosomal escape. sCA-survivin-siRNA induced apoptosis in HT29 tumors and significantly inhibited <i>in vivo</i> tumor growth of HCT116, to a greater extent than two other <i>in vivo</i> delivery reagents. With innovative <i>in vivo</i> delivery efficiency, sCA could be a useful nanoparticle for the therapy of solid tumors.</p>