Targeted nanoparticle-mediated LHPP for melanoma treatment
Authors Zhang Q, Xiong M, Liu J, Wang S, Du T, Kang T, Liu Y, Cheng H, Huang M, Gou M
Received 29 November 2018
Accepted for publication 12 March 2019
Published 10 May 2019 Volume 2019:14 Pages 3455—3468
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Linlin Sun
Qianqian Zhang,1,2,* Meimei Xiong,2,* Jinlu Liu,1,2 Shuai Wang,2 Ting Du,2 Tianyi Kang,2 Yu Liu,2 Hao Cheng,2 Meijuan Huang,1 Maling Gou2
1Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China
*These authors contributed equally to this work
Background: 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.
Methods: A CRGDKGPDC peptide (iRGD) modified hybrid monomethoxy poly(ethylene glycol)-poly(D,L-lactide) nanoparticle (iDPP) was prepared and complexed with a LHPP plasmid, forming an iDPP/LHPP nanocomplex. The iDPP/LHPP 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/LHPP nanocomplex were evaluated.
Results: The iDPP/LHPP 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/LHPP nanocomplex significantly inhibited the melanoma growth without causing notable adverse effects. We also found that LHPP played an important role in epigenetics. It regulated the expression of genes related to the proliferation and apoptosis chiefly at the level of transcription.
Conclusion: This work demonstrates that the iDPP nanoparticle-delivered LHPP gene has a potential application in melanoma therapy through regulation of the genes associated with epigenetics.
Keywords: melanoma, LHPP, nanoparticle, gene therapy, epigenetics