Targeted Gene Silencing BRAF Synergized Photothermal Effect Inhibits Hepatoma Cell Growth Using New GAL-GNR-siBRAF
Yanling Liu1,2,3, Manman Tan4, Yujuan Zhang4
1Institute of Immunotherapy, Nanchang University, Nanchang, 330006, Jiangxi, China. liuyanling614@163.com.
Abstract:
Liver cancer is one of the most common malignancies worldwide. The RAF kinase inhibitors are effective in the treatment of hepatocellular carcinoma (HCC); therefore, inhibition of the BRAF/MEK/ERK pathway has become a new therapeutic strategy for novel HCC therapy. However, targeted specific delivery systems for tumors are still significant obstacle to clinical applications. Galactose (GAL) can target the asialoglycoprotein receptor (ASGPR) that is highly expressed on liver cancer cells. In this study, we designed a novel multifunctional nanomaterial GAL-GNR-siBRAF which consists of three parts, GAL as the liver cancer-targeting moiety, golden nanorods (GNR) offering photothermal capability under near infrared light, and siRNA specifically silencing BRAF (siBRAF). The nanocarrier GAL-GNR-siBRAF showed high siRNA loading capacity and inhibited the degradation of siRNA in serum. Compared with naked gold nanorods, GAL-GNR-siBRAF possessed lower biotoxicity and higher efficacy of gene silencing. Treatment with GAL-GNR-siBRAF significantly downregulated the expression of BRAF and impaired proliferation, migration, and invasion of liver cancer cells. Moreover, combinatorial photothermal effects and BRAF knockdown by GAL-GNR-siBRAF effectively given rise to tumor cell death. Therefore, our study developed a new type of targeted multi-functional nanomaterial GAL-GNR-siBRAF for the treatment of liver cancer, which provides ideas for the development of new clinical treatment methods.
Insights
This study presents GAL-GNR-siBRAF, a novel nanomaterial targeting liver cancer cells. It combines galactose targeting, golden nanorods for photothermal therapy, and BRAF gene silencing for effective hepatocellular carcinoma treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) is a prevalent global malignancy.
- Targeted therapies for HCC face challenges in drug delivery.
- The BRAF/MEK/ERK pathway is a key target for HCC treatment.
Purpose of the Study:
- To develop a multifunctional nanomaterial for targeted liver cancer therapy.
- To investigate the efficacy of GAL-GNR-siBRAF in inhibiting hepatocellular carcinoma growth.
- To explore the combined effects of photothermal therapy and gene silencing.
Main Methods:
- Design and synthesis of GAL-GNR-siBRAF nanomaterial.
- In vitro evaluation of siRNA loading, stability, and gene silencing efficacy.
- Assessment of cytotoxicity and anti-cancer effects on liver cancer cells.
- In vivo evaluation of therapeutic efficacy using photothermal effects and BRAF knockdown.
Main Results:
- GAL-GNR-siBRAF demonstrated high siRNA loading capacity and stability.
- The nanomaterial exhibited lower biotoxicity and enhanced gene silencing compared to naked gold nanorods.
- Treatment significantly reduced BRAF expression, proliferation, migration, and invasion of liver cancer cells.
- Combined photothermal therapy and BRAF knockdown induced significant tumor cell death.
Conclusions:
- GAL-GNR-siBRAF is a promising targeted nanomaterial for liver cancer treatment.
- The study provides a novel strategy for combining photothermal therapy and gene silencing.
- This approach offers potential for developing new clinical therapies for hepatocellular carcinoma.
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