2.B.133.  The cRGD-R9-PEG-PEI-Cholesterol Nano-Congugate Delivery System                     (rrPPC-NCDS) Family

Treatment of colon cancer has been achieved using degradable rrPPC nano-conjugates. This delivery system has delivered STAT3 siRNA to colon cancer cells (Zhang et al. 2020).  Drugs that work on cancer cells based on the mechanism of RNA interference provide a cancer gene therapy approach. Although significant progress has been made in small interfering RNA (siRNA) design and manufacturing, an ideal delivery system remains a limitation for the development of siRNA-based drugs.  The synthesized rrPPC was dispersed as nanoparticles in water with an average size of 195 nm and 41.9 mV in potential. rrPPC nanoparticles could efficiently deliver siRNA into C26 clone cancer cells and trigger caveolae-mediated pathway during transmembrane transport.  By loading the signal transducer and activator of transcription 3 (STAT3) targeting siRNA, rrPPC/STAT3 siRNA (rrPPC/siSTAT3) complex demonstrated strong anti-cancer effects in multiple colon cancer models following local delivery. In addition, intravenous (IV) injection of rrPPC/siSTAT3 complex efficiently suppressed lung metastasis tumor progression with ideal in vivo safety. Thus, rrPPC nanoparticles constitute a candidate vector for siRNA-based colon cancer gene therapy (Zhang et al. 2020).