Anti-tumor Efficiency of Lipid-coated Cisplatin Nanoparticles Co-loaded with MicroRNA-375.

Abstract:

:One of the major challenges in the hepatocellular carcinoma (HCC) treatment is its insensitivity to chemotherapeutic drugs. Here, we report the development of novel lipid-coated cisplatin nanoparticles co-loaded with microRNA-375 (NPC/miR-375) as a potential treatment for chemotherapy insensitive HCC. The NPC/miR-375 was fabricated by mixing two reverse microemulsions containing KCl solution and a highly soluble cis-diaminedihydroplatinum (II) coated with a cationic lipid layer. Subsequently, the miR-375 was incorporated into the lipid-coated cisplatin nanoparticles. The NPC/miR375 nanoparticles were expected to further decrease cell proliferation and to enhance the anti-tumor effect of cisplatin in chemotherapy resistant HCC cells. In vitro analysis of intracellular trafficking revealed that NPC/miR-375 were able to escape from the late endosomes instead of lysosomes thus avoiding degradation of the miR-375 in lysosomes. Importantly, NPC/miR-375 enhanced apoptosis and induced cell cycle arrest in HCC cells in vitro. In the double oncogenes Akt/Ras-induced primary HCC mouse model, multiple doses of NPC/miR-375 significantly inhibited tumor growth and delayed the tumor relapse. Our results indicate that cisplatin nanoparticles co-loaded with miR-375 represent a potential therapeutic agent for chemotherapy-insensitive HCC.

journal_name

Theranostics

journal_title

Theranostics

authors

Yang T,Zhao P,Rong Z,Li B,Xue H,You J,He C,Li W,He X,Lee RJ,Ma X,Xiang G

doi

10.7150/thno.13130

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

142-54

issue

1

issn

1838-7640

pii

thnov06p0142

journal_volume

6

pub_type

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