Efficient and targeted chemo-gene delivery with self-assembled fluoro-nanoparticles for liver fibrosis therapy and recurrence
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.
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CXCL1 has been shown to be associated with HSCs migration and survival.
“In addition to promoting HSCs proliferation, CXCL1 has been shown to be associated with HSCs migration and survival.[ 29 ]”
From An Autologous Macrophage‐Based Phenotypic Transformation‐Collagen Degradation System Treating Advanced Liver Fibrosis (2024) · cites this paper as [29]
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- Authors
- Wu, P., Luo, X., Wu, H., Zhang, Q., Dai, Y., & Sun, M.
- Affiliations
- China Pharmaceutical University (CN)
- Corresponding author
- Sun, Minjie
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 261
- Pages
- 120311
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W3047943181
- Cited by
- 37
- References
- 51
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 10 · 2021: 3
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- liver fibrosis, nanoparticle self-assembly, fluorinated polymers, sorafenib, hepatic stellate cells, Kupffer cells, macrophage polarization, drug delivery, early intervention
- MeSH terms
- Pharmaceutical Preparations, Fibrosis, Humans, Liver, Liver Cirrhosis, Genetic Therapy, Nanoparticles
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