Related Experiment Video
Updated: Dec 9, 2025
Isolation of Primary Cancer-Associated Fibroblasts from a Syngeneic Murine Model of Breast Cancer for the Study of Targeted Nanoparticles
Published on: May 14, 2021
Efficient and targeted chemo-gene delivery with self-assembled fluoro-nanoparticles for liver fibrosis therapy and
Pengkai Wu1, Xinping Luo1, Hui Wu1
1State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.
Abstract:
The treatment options of liver fibrosis remain limited except for liver transplantation due to the complexity and slow development in its progression. Besides, liver fibrosis recurrence and intervention time have not been reported as significant indicators to affect the anti-fibrotic efficacy of tested drugs/strategies. Herein, a novel fluoropolymer is developed to achieve high drug loading of sorafenib and efficient delivery of miR155 inhibitor (anti-miR155) for dual-targeting of hepatic stellate cells (HSCs) and kupffer cells (KCs), and we report a detailed plan on the design of treatment regimen to reveal the relationship between chemogene therapy, intervention time and fibrosis recurrence. Such a combined chemo-gene therapy of sorafenib and anti-miR155 can achieve superior therapeutic efficiency by polarizing the pro-inflammatory M1 to anti-inflammatory M2 of KCs and inhibiting the proliferation of HSCs. Importantly, efficacy and recurrence prevention of chemogene therapy earlier in the liver fibrosis will be more effective than the treatment at later stage. In conclusion, this work proposes a novel strategy to improve the efficacy and prevent recurrence of liver fibrosis by dual-regulating of KCs and HSCs, and emphasizes the importance of therapy earlier in the treatment of liver fibrosis.
Insights
This study introduces a novel dual-targeting therapy for liver fibrosis using sorafenib and an miR155 inhibitor. Early intervention with this chemogene therapy shows improved efficacy and recurrence prevention by regulating hepatic stellate cells (HSCs) and Kupffer cells (KCs).
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Hepatology
Background:
- Liver fibrosis treatment options are limited, with transplantation being the primary choice.
- Fibrosis progression is complex, and recurrence/intervention timing are understudied factors impacting therapy efficacy.
Purpose of the Study:
- To develop a novel fluoropolymer for co-delivery of sorafenib and anti-miR155.
- To investigate the relationship between chemogene therapy, intervention timing, and liver fibrosis recurrence.
- To evaluate the dual-targeting efficacy on hepatic stellate cells (HSCs) and Kupffer cells (KCs).
Main Methods:
- Design of a novel fluoropolymer for high drug loading and efficient delivery.
- Co-delivery of sorafenib (chemotherapy) and miR155 inhibitor (gene therapy).
- Dual-targeting of HSCs and KCs for synergistic anti-fibrotic effects.
Main Results:
- The combined therapy demonstrated superior therapeutic efficiency.
- Pro-inflammatory M1 Kupffer cells were polarized to anti-inflammatory M2 phenotype.
- HSC proliferation was significantly inhibited.
- Early-stage intervention proved more effective for efficacy and recurrence prevention.
Conclusions:
- A novel chemogene therapy strategy improves liver fibrosis treatment efficacy and prevents recurrence.
- Dual-regulation of KCs and HSCs is key to the therapeutic success.
- Emphasizes the critical importance of early intervention in liver fibrosis treatment.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...