A multifunctional nanocarrier for efficient TRAIL‐based gene therapy against hepatocellular carcinoma with desmoplasia in mice | Zendy

Liu ChunHung | Zendy; Chern GuannJen | Zendy; Hsu FuFei | Zendy; Huang KuanWei | Zendy; Sung YunChieh | Zendy; Huang HsiChien | Zendy; Qiu Jiantai Timothy | Zendy; Wang ShengKai | Zendy; Lin ChuChi | Zendy; Wu ChienHsun | Zendy; Wu HanChung | Zendy; Liu JiaYu | Zendy; Chen Yunching | Zendy

Premium

A multifunctional nanocarrier for efficient TRAIL‐based gene therapy against hepatocellular carcinoma with desmoplasia in mice

Author(s) -

Liu ChunHung,

Chern GuannJen,

Hsu FuFei,

Huang KuanWei,

Sung YunChieh,

Huang HsiChien,

Qiu Jiantai Timothy,

Wang ShengKai,

Lin ChuChi,

Wu ChienHsun,

Wu HanChung,

Liu JiaYu,

Chen Yunching

Publication year - 2018

Publication title -

hepatology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.488

H-Index - 361

eISSN - 1527-3350

pISSN - 0270-9139

DOI - 10.1002/hep.29513

Subject(s) - hepatic stellate cell , hepatocellular carcinoma , sorafenib , cancer research , nanocarriers , genetic enhancement , apoptosis , hccs , medicine , hepatology , pharmacology , chemistry , biochemistry , drug , gene

The anticancer efficacy of TNF‐related apoptosis‐inducing ligand (TRAIL)‐based therapy is limited because of systemic toxicity, poor bioavailability, and development of TRAIL resistance. We developed a tumor‐targeted LCPP (lipid/calcium/phosphate/protamine) nanoparticle (NP) to deliver TRAIL plasmid DNA (pDNA) into hepatocellular carcinoma (HCC) cells in a mouse model of HCC. TRAIL pDNA was encapsulated in a pH stimuli‐responsive calcium phosphate (CaP) core, and protamine was added to facilitate nuclear delivery of pDNA. In addition, intracellular release of Ca 2+ from the CaP core overcame TRAIL resistance by calcium influx‐dependent DR5 up‐regulation. TRAIL expression also attenuated fibrosis in liver tissues surrounding HCCs by reverting activated hepatic stellate cells (HSCs) to a quiescent state or by directly inducing apoptosis in activated HSCs. Conclusion: TRAIL pDNA delivered by HCC‐targeted LCPP NPs in combination with conventional sorafenib treatment attenuated HCC progression as well as liver fibrosis. Overall, our study presents an effective TRAIL‐based cancer therapy that could be developed for clinical applications. (H epatology 2018;67:899–913)

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here

Accelerating Research