iRGD-conjugated DSPE-PEG2000 nanomicelles for targeted delivery of salinomycin for treatment of both liver cancer cells and cancer stem cells

Xiaoli Mao; Junjie Liu; Zhirong Gong; He Zhang; Ying Lu; Hao Zou; Yuan Yu; Yan Chen; Zhiguo Sun; Wei Li; Bohua Li; Jie Gao; Yanqiang Zhong

doi:10.2217/nnm.15.106

iRGD-conjugated DSPE-PEG2000 nanomicelles for targeted delivery of salinomycin for treatment of both liver cancer cells and cancer stem cells

Nanomedicine (Lond). 2015;10(17):2677-95. doi: 10.2217/nnm.15.106. Epub 2015 Sep 10.

Authors

Xiaoli Mao^{1

2}, Junjie Liu¹, Zhirong Gong¹, He Zhang¹, Ying Lu^{1

2}, Hao Zou¹, Yuan Yu¹, Yan Chen¹, Zhiguo Sun¹, Wei Li³, Bohua Li³, Jie Gao¹, Yanqiang Zhong^{1

2}

Affiliations

¹ Department of Pharmaceutical Sciences, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
² School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian, China.
³ International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.

PMID: 26355733
DOI: 10.2217/nnm.15.106

Abstract

Aims: To develop novel iRGD (internalizing Arg-Gly-Asp peptide)-conjugated DSPE-PEG2000 nanomicelles (M-SAL-iRGD) for delivery of salinomycin to both liver cancer cells and cancer stem cells (CSCs).

Materials & methods: The characterization, antitumor activity and mechanism of action of M-SAL-iRGD were evaluated.

Results & conclusion: M-SAL-iRGD possessed a small size of around 10 nm, and drug encapsulation efficacy higher than 90%. M-SAL-iRGD showed significantly increased cytotoxic effect toward both nontargeted M-SAL (salinomycin-loaded DSPE-PEG2000 nanomicelles) and salinomycin in both liver cancer cells and CSCs. The tissue distribution and antitumor assays in mice bearing liver cancer xenograft confirmed the superior penetration tumor efficacy and antitumor activity of M-SAL-iRGD. M-SAL-iRGD represent a potential effective nanomedicine against liver cancer.

Keywords: cancer nanotechnology; cancer stem cells; iRGD; liver cancer; micelles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AC133 Antigen
Animals
Antigens, CD / metabolism
Cell Line, Tumor
Drug Carriers / chemistry
Drug Delivery Systems*
Gene Expression Regulation, Neoplastic
Glycoproteins / metabolism
Hep G2 Cells
Humans
Liposomes / chemistry
Liver Neoplasms / drug therapy*
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Micelles*
Nanomedicine
Neoplasm Metastasis
Neoplasm Transplantation
Neoplastic Stem Cells / drug effects*
Neuropilin-1 / metabolism
Oligopeptides / chemistry*
Peptides / metabolism
Phosphatidylethanolamines / chemistry*
Polyethylene Glycols / chemistry*
Pyrans / administration & dosage*
Pyrans / chemistry
Rats
Rats, Sprague-Dawley
Tissue Distribution

Substances

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)
AC133 Antigen
Antigens, CD
Drug Carriers
Glycoproteins
Liposomes
Micelles
Oligopeptides
Peptides
Phosphatidylethanolamines
Pyrans
Neuropilin-1
Polyethylene Glycols
salinomycin
arginyl-glycyl-aspartic acid