Targeted nanoparticle-mediated LHPP for melanoma treatment

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a novel tumor suppressor. However, whether LHPP is effective to melanoma has not been investigated. Gene therapy provides a new strategy for the treatment of melanoma. Currently, it suffers from the lack of safe and effecti...

Full description

Saved in:
Bibliographic Details
Published in:International journal of nanomedicine 2019-05, Vol.14, p.3455-3468
Main Authors: Zhang, Qianqian, Xiong, Meimei, Liu, Jinlu, Wang, Shuai, Du, Ting, Kang, Tianyi, Liu, Yu, Cheng, Hao, Huang, Meijuan, Gou, Maling
Format: Article
Language:English
Subjects:
Cancer treatment
Drug therapy
EDTA
Epigenetic inheritance
Epigenetics
Ethylene glycols
Gene therapy
Genes
Glycols (Class of compounds)
Infection
LHPP
Melanoma
Nanoparticle
Novels
Original Research
Peptides
Phosphatases
Phosphates
Toxicity
Transcription (Genetics)
Tumors
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a novel tumor suppressor. However, whether LHPP is effective to melanoma has not been investigated. Gene therapy provides a new strategy for the treatment of melanoma. Currently, it suffers from the lack of safe and effective gene delivery systems. A CRGDKGPDC peptide (iRGD) modified hybrid monomethoxy poly(ethylene glycol)-poly(D,L-lactide) nanoparticle (iDPP) was prepared and complexed with a plasmid, forming an iDPP/ nanocomplex. The iDPP/ nanocomplex was characterized by particle size distribution, zeta potential, morphology, cytotoxicity, and transfection efficiency. The antitumor efficacy of the nanocomplex against melanoma was studied both in vitro and in vivo. Further, the potential epigenetic changes in melanoma induced by iDPP/ nanocomplex were evaluated. The iDPP/ nanocomplex showed high transfection efficiency and low toxicity. Moreover, the nanocomplex displayed a neutral charge that can meet the requirement of intravenous injection for targeted gene therapy. In vitro and in vivo experiments indicated that the iDPP/ nanocomplex significantly inhibited the melanoma growth without causing notable adverse effects. We also found that played an important role in epigenetics. It regulated the expression of genes related to the proliferation and apoptosis chiefly at the level of transcription. This work demonstrates that the iDPP nanoparticle-delivered gene has a potential application in melanoma therapy through regulation of the genes associated with epigenetics.
ISSN:1178-2013
1176-9114
1178-2013
DOI:10.2147/IJN.S196374