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.