Sustained and targeted delivery of siRNA/DP7-C nanoparticles from injectable thermosensitive hydrogel for
Binyan Zhao1, Bailing Zhou1, Kun Shi1
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
Abstract:
Hepatocellular carcinoma (HCC) is one of the most lethal cancers in humans. The inhibition of peptidyl-prolyl cis/trans isomerase (Pin1) gene expression may have great potential in the treatment of HCC. N-Acetylgalactosamine (GalNAc) was used to target the liver. Cholesterol-modified antimicrobial peptide DP7 (DP7-C) acts as a carrier, the GalNAc-siRNA/DP7-C complex increases the uptake of GalNAc-siRNA and the escape of endosomes in hepatocytes. In addition, DP7-C nanoparticles and hydrogel-assisted GalNAc-Pin1 siRNA delivery can effectively enhance the stability and prolong the silencing effects of Pin1 siRNA. In an orthotopic liver cancer model, the GalNAc-Pin1 siRNA/DP7-C/hydrogel complex can potentially regulate Pin1 expression in hepatocellular carcinoma cells and effectively inhibit tumor progression. Our study proves that Pin1 siRNA is an efficient method for the treatment of HCC and provides a sustainable and effective drug delivery system for the suppression of liver cancer.
Insights
Inhibiting peptidyl-prolyl cis/trans isomerase (Pin1) with siRNA shows promise for treating hepatocellular carcinoma (HCC). A novel drug delivery system enhances Pin1 siRNA stability and effectiveness in liver cancer models.
Area of Science:
- Oncology
- Biotechnology
- Drug Delivery
Background:
- Hepatocellular carcinoma (HCC) is a highly lethal cancer.
- Pinpointing peptidyl-prolyl cis/trans isomerase (Pin1) as a therapeutic target offers potential for HCC treatment.
Purpose of the Study:
- To investigate the efficacy of Pin1 siRNA for HCC treatment.
- To develop a sustainable and effective drug delivery system for Pin1 siRNA in liver cancer.
Main Methods:
- Utilized N-Acetylgalactosamine (GalNAc) for liver targeting.
- Employed cholesterol-modified antimicrobial peptide DP7 (DP7-C) as a carrier for GalNAc-Pin1 siRNA.
- Developed DP7-C nanoparticles and hydrogel-assisted delivery systems.
- Evaluated the complex in an orthotopic liver cancer model.
Main Results:
- The GalNAc-siRNA/DP7-C complex enhanced hepatocyte uptake and endosomal escape.
- DP7-C nanoparticles and hydrogel improved Pin1 siRNA stability and prolonged silencing effects.
- The GalNAc-Pin1 siRNA/DP7-C/hydrogel complex effectively regulated Pin1 expression and inhibited tumor progression in vivo.
Conclusions:
- Pin1 siRNA demonstrates significant potential as an efficient therapeutic strategy for HCC.
- The developed drug delivery system offers a sustainable and effective approach for liver cancer suppression.
