Hyperbranched lipoid-based lipid nanoparticles for bidirectional regulation of collagen accumulation in liver fibrosis

Qiao, Jian-Bin; Fan, Qianqian; Zhang, Chenglu; Lee, Jaiwoo; Byun, Ji Won; Liu, Xing; Gao, Xiangdong; Oh, Yu‐Kyoung; Jiang, Hu‐Lin

doi:10.1016/j.jconrel.2020.02.049

Cited by 48 publications

(36 citation statements)

References 45 publications

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“…As the buffering capacity of polymers is known to predict lysosomal escape in cells, we investigated the buffering capacity in vitro by acid–base titration. [ 28 ] The data showed that the pH change was gradual and continuous in the TISUH group, suggesting that TISUH had a certain buffering capability (Figure S8A, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Pathologically Responsive Mitochondrial Gene Therapy in an Allotopic Expression‐Independent Manner Cures Leber's Hereditary Optic Neuropathy

Wang

Cui

et al. 2021

Advanced Materials

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Leber's hereditary optic neuropathy (LHON) is a rare inherited blindness caused by mutations in the mitochondrial DNA (mtDNA). The disorder is untreatable and tricky, as the existing chemotherapeutic agent Idebenone alleviates symptoms rather than overcoming the underlying cause. Although some studies have made progress on allotopic expression for LHON, in situ mitochondrial gene therapy remains challenging, which may simplify delivery procedures to be a promising therapeutic for LHON. LHON becomes more difficult to manage in the changed mitochondrial microenvironment, including increasing reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP). Herein, a pathologically responsive mitochondrial gene delivery vector named [triphenylphosphine‐terminated poly(sulfur‐containing thioketal undecafluorohexylamine histamine) and Ide‐terminated poly(sulfur‐containing thioketal undecafluorohexylamine histamine)] (TISUH) is reported to facilitate commendable in situ mitochondrial gene therapy for LHON. TISUH directly targets diseased mitochondria via triphenylphosphine and fluorination addressing the decreasing MMP. In addition, TISUH can be disassembled by high mitochondrial ROS levels to release functional genes for enhancing gene transfection efficiency and fundamentally correcting genetic abnormalities. In both traditional and gene‐mutation‐induced LHON mouse models, TISUH‐mediated gene therapy shows satisfactory curative effect through the sustained therapeutic protein expression in vivo. This work proposes a novel pathologically responsive in situ mitochondrial delivery platform and provides a promising approach for refractory LHON as well as other mtDNA mutated diseases treatments.

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Section: Resultsmentioning

confidence: 99%

Pathologically Responsive Mitochondrial Gene Therapy in an Allotopic Expression‐Independent Manner Cures Leber's Hereditary Optic Neuropathy

Wang

Cui

et al. 2021

Advanced Materials

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“…Qiao et al reported the synthesis and in vivo evaluation of VitA-lipoplexes consisting of amphiphilic cationic hyperbranched lipidoids and helper lipoids (cholesterol-polyethylene glycol-vitamin A, Chol-PEG-vitamin A) as siRNA carrier for HSC specific targeting ( Table 2 ) [ 118 ]. In co-culture experiments for cellular uptake, fluorescence-labeled and siRNA loaded VitA-lipoplexes were efficiently taken up by the rat HSC-T6 cell line, while uptake was low in macrophages (RAW cell line).…”

Section: Cell Specific Targeting Of Caf With Nanoparticlesmentioning

confidence: 99%

“…After intravenous injection, near infrared dye-labeled VitA-lipoplexes showed an enhanced accumulation in fibrotic compared to non-fibrotic livers or control lipoplexes without targeting ligand. Morphometrical collagen quantification revealed that VitA-derivatized lipoplexes carrying both anticol1a1 and antitimp1 siRNA reduced hepatic collagen accumulation more efficiently (~2-fold) than lipoplexes carrying either anticol1a1 or antitimp1 siRNA alone [ 118 ]. A caveat to the efficacy of vitamin A loaded nanoparticles for HSC targeting in advanced fibrosis is the finding that with fibrogenic activation, HSC lose their vitamin A stores and likely their ability to ingest vitamin A via RBP receptors.…”

Section: Cell Specific Targeting Of Caf With Nanoparticlesmentioning

confidence: 99%

Targeting Cancer Associated Fibroblasts in Liver Fibrosis and Liver Cancer Using Nanocarriers

Kaps

Schuppan

2020

Cells

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Cancer associated fibroblasts (CAF) and the extracellular matrix (ECM) produced by them have been recognized as key players in cancer biology and emerged as important targets for cancer treatment and drug discovery. Apart from their presence in stroma rich tumors, such as biliary, pancreatic and subtypes of hepatocellular cancer (HCC), both CAF and certain ECM components are also present in cancers without an overt intra-tumoral desmoplastic reaction. They support cancer development, growth, metastasis and resistance to chemo- or checkpoint inhibitor therapy by a multitude of mechanisms, including angiogenesis, ECM remodeling and active immunosuppression by secretion of tumor promoting and immune suppressive cytokines, chemokines and growth factors. CAF resemble activated hepatic stellate cells (HSC)/myofibroblasts, expressing α-smooth muscle actin and especially fibroblast activation protein (FAP). Apart from FAP, CAF also upregulate other functional cell surface proteins like platelet-derived growth factor receptor β (PDGFRβ) or the insulin-like growth factor receptor II (IGFRII). Notably, if formulated with adequate size and zeta potential, injected nanoparticles home preferentially to the liver. Several nanoparticular formulations were tested successfully to deliver dugs to activated HSC/myofibroblasts. Thus, surface modified nanocarriers with a cyclic peptide binding to the PDGFRβ or with mannose-6-phosphate binding to the IGFRII, effectively directed drug delivery to activated HSC/CAF in vivo. Even unguided nanohydrogel particles and lipoplexes loaded with siRNA demonstrated a high in vivo uptake and functional siRNA delivery in activated HSC, indicating that liver CAF/HSC are also addressed specifically by well-devised nanocarriers with optimized physicochemical properties. Therefore, CAF have become an attractive target for the development of stroma-based cancer therapies, especially in the liver.

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“…The innovation point was that we explored the process conditions of each stage that affect its performance, and under the appropriate raw material ratio and calcination conditions, we prepared the ideal nanomaterials. At the same time, as the most important detoxification organ of the human body, the liver played a significant role in the recognition and transport of nanoparticles into the human body [27,28], so we selected the human normal hepatocytes L-02 as the research object to investigate the cytotoxicity of magnetic α-Fe 2 O 3 /Fe 3 O 4 heterogeneous nanoparticles. The blood routine and histopathological section observation of mice injected magnetic α-Fe 2 O 3 /Fe 3 O 4 heterogeneous nanoparticles through the tail vein were detected.…”

Section: Introductionmentioning

confidence: 99%

Superparamagnetic α-Fe2O3/Fe3O4 Heterogeneous Nanoparticles with Enhanced Biocompatibility

Wang

Liu

2021

Nanomaterials

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A novel type of magnetic α-Fe2O3/Fe3O4 heterogeneous nanoparticles was prepared via a facile solution combustion process with ferric nitrate and urea as raw materials, and they were characterized by XRD, SEM, TEM, and VSM techniques. The effects of the calcination temperature, the calcination time, the ratio of ferric nitrate and urea, and the heating rate on the relative content of Fe3O4 in the heterogeneous nanoparticles were investigated. The toxicity of α-Fe2O3/Fe3O4 heterogeneous nanoparticles to human hepatocytes L-02, the blood routine, and the histopathological section observation of mice were explored. The results showed that the ratio of ferric nitrate and urea was a key factor to affect the relative content of Fe3O4 in the heterogeneous nanoparticles. The calcination temperature and the calcination time had similar influences, and the corresponding calcination temperature and the calcination time were selected according to their own needs. The CCK8 results initially revealed that α-Fe2O3/Fe3O4 heterogeneous nanoparticles had no effect on cell viability when the concentration of the heterogeneous nanoparticles was less than 100 ng/mL, which suggested their excellent biocompatibility. At the same time, the tail vein administration concentration of 0.9 mg/kg had good biological safety.

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Hyperbranched lipoid-based lipid nanoparticles for bidirectional regulation of collagen accumulation in liver fibrosis

Cited by 48 publications

References 45 publications

Pathologically Responsive Mitochondrial Gene Therapy in an Allotopic Expression‐Independent Manner Cures Leber's Hereditary Optic Neuropathy

Pathologically Responsive Mitochondrial Gene Therapy in an Allotopic Expression‐Independent Manner Cures Leber's Hereditary Optic Neuropathy

Targeting Cancer Associated Fibroblasts in Liver Fibrosis and Liver Cancer Using Nanocarriers

Superparamagnetic α-Fe2O3/Fe3O4 Heterogeneous Nanoparticles with Enhanced Biocompatibility

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