TRAIL and curcumin codelivery nanoparticles enhance TRAIL-induced apoptosis through upregulation of death receptors

Xi Yang; Zhaojun Li; Qinjie Wu; Shouchun Chen; Cheng Yi; Changyang Gong

doi:10.1080/10717544.2017.1384863

TRAIL and curcumin codelivery nanoparticles enhance TRAIL-induced apoptosis through upregulation of death receptors

Drug Deliv. 2017 Nov;24(1):1526-1536. doi: 10.1080/10717544.2017.1384863.

Authors

Xi Yang¹, Zhaojun Li^{1

2}, Qinjie Wu¹, Shouchun Chen³, Cheng Yi¹, Changyang Gong¹

Affiliations

¹ a Department of Medical Oncology, Cancer Center, and State Key Laboratory of Biotherapy , West China Hospital, Sichuan University , Chengdu , China.
² b Department of Radiotherapy , Hainan General Hospital , Haikou , China.
³ c Chengdu Huachuang Biotechnology Co. Ltd , Chengdu , China.

Abstract

Active targeting nanoparticles were developed to simultaneously codeliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Curcumin (Cur). In the nanoparticles (TRAIL-Cur-NPs), TRAIL was used as both active targeting ligand and therapeutic agent, and Cur could upregulate death receptors (DR4 and DR5) to increase the apoptosis-inducing effects of TRAIL. Compared with corresponding free drugs, TRAIL-Cur-NPs group showed enhanced cellular uptake, cytotoxicity and apoptosis induction effect on HCT116 colon cancer cells. In addition, in vivo anticancer studies suggested that TRAIL-Cur-NPs had superior therapeutic effect on tumors without obvious toxicity, which was mainly due to the high tumor targeting and synergistic effect of TRAIL and Cur. The synergistic mechanism of improved antitumor efficacy was proved to be upregulation of DR4 and DR5 in tumor cells induced by Cur. Thus, the prepared codelivery nanoparticles may have potential applications in colorectal cancer therapy.

Keywords: TRAIL; apoptosis; codelivery; curcumin; death receptors; nanoparticles.

MeSH terms

Apoptosis / drug effects*
Curcumin
Drug Liberation
Drug Synergism
Gene Expression
HCT116 Cells
Humans
Nanoparticles / administration & dosage*
Particle Size
Receptors, Death Domain / drug effects
Receptors, Death Domain / genetics
Surface Properties
TNF-Related Apoptosis-Inducing Ligand / pharmacokinetics
TNF-Related Apoptosis-Inducing Ligand / pharmacology*
Up-Regulation

Substances

Receptors, Death Domain
TNF-Related Apoptosis-Inducing Ligand
Curcumin

Grants and funding

This work was supported by the National Nature Science Foundation of China under Grant (No. 81301962 and No.81372444) and National Program for Support of Top-notch Young Professionals.