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Innovative delivery of siRNA to solid tumors by super carbonate apatite
Xin Wu1, Hirofumi Yamamoto2, Hiroyuki Nakanishi3
1Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan; Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan.
Abstract:
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 in vivo 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 in vivo tumor growth of HCT116, to a greater extent than two other in vivo delivery reagents. With innovative in vivo delivery efficiency, sCA could be a useful nanoparticle for the therapy of solid tumors.
Insights
Super carbonate apatite (sCA) nanoparticles offer a novel pH-sensitive system for delivering small interfering RNA (siRNA) directly to solid tumors. This breakthrough enables effective in vivo tumor growth inhibition with minimal adverse events.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- RNA interference (RNAi) holds therapeutic potential but faces challenges in systemic delivery to solid tumors.
- Effective delivery of small interfering RNA (siRNA) to solid tumors remains a significant hurdle in clinical applications.
Purpose of the Study:
- To develop and evaluate a novel pH-sensitive nanoparticle system for in vivo siRNA delivery to solid tumors.
- To assess the efficacy and safety of super carbonate apatite (sCA) nanoparticles for cancer therapy.
Main Methods:
- Development of super carbonate apatite (sCA) nanoparticles as a nanocarrier for siRNA.
- Evaluation of sCA-siRNA accumulation, endosomal escape, and tumor growth inhibition in vivo.
- Assessment of adverse events in preclinical models (mice and monkeys).
Main Results:
- sCA nanoparticles demonstrated specific tumor accumulation and rapid cytoplasmic delivery of siRNA.
- sCA-survivin-siRNA induced apoptosis and significantly inhibited tumor growth in HCT116 models.
- The sCA delivery system showed no serious adverse events in mice and monkeys.
Conclusions:
- Super carbonate apatite (sCA) nanoparticles represent a promising, pH-sensitive nanocarrier for effective in vivo siRNA delivery to solid tumors.
- sCA nanoparticles offer a potential new strategy for solid tumor therapy with high delivery efficiency and safety.
