Enhanced anti-cancer activity by co-delivery of docetaxel and perifosine with multifunctional nanoparticles via regulation of PI3K/Akt signalling pathway

Author

Jingjing Chen ; Xiangyuan Bu ; Qi Shen

Author_Institution

Sch. of Pharmacy, Shanghai Jiao Tong Univ., Shanghai, China

Volume

10

Issue

5

fYear

2015

fDate

5 2015

Firstpage

253

Lastpage

257

Abstract

Recent researches revealed that phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) plays an important role in the development of drug resistance, reducing the anti-tumour activity of cytotoxic drugs, such as docetaxel (DTX). The aim of this reported work has been to evaluate DTX and the PI3K/Akt inhibitor perifosine co-loaded Fol/R₇ (folate/R₇) nanoparticles (NPs) for enhancing anti-cancer activity. The NPs were evaluated by size, zeta potential and morphology. Then cell viability, cellular uptake and apoptosis were performed in MCF-7 and MCF-7/Adr cells. The PI3K/Akt inhibition effect was assessed by western blotting. Compared with other experimental groups, DTX and perifosine loaded Fol/R₇ NPs displayed the highest cytotoxicity, cell uptake and early apoptosis in MCF-7/Adr cells. Furthermore, the PI3K/Akt inhibition effect was enhanced by the Fol/R₇ NPs compared with the free drug group. The DTX and perifosine co-loaded Fol/R₇ NPs could be a potential, safe and efficient option for enhancing anti-cancer activity.

Keywords

biomedical materials; cancer; cellular biophysics; drug delivery systems; drugs; electrokinetic effects; nanomedicine; nanoparticles; tumours; DTX antitumor activity; DTX evaluation; DTX loaded Fol-R7 nanoparticle cell uptake; DTX loaded Fol-R7 nanoparticle cytotoxicity; DTX loaded Fol-R7 nanoparticle early apoptosis; Fol-R7 NP-enhanced PI3K-Akt inhibition effect; MCF-7 apoptosis; MCF-7 cell viability; MCF-7 cellular uptake; MCF-7-Adr apoptosis; MCF-7-Adr cell viability; MCF-7-Adr cellular uptake; PI3K-Akt inhibition effect assessment; PI3K-Akt inhibitor nanoparticle; PI3K-Akt-associated drug resistance; PI3K/Akt signalling pathway regulation; Western blotting-assessed P13K-Akt inhibition; cytotoxic drug antitumor activity; docetaxel antitumor activity; docetaxel codelivery; docetaxel evaluation; drug resistance development; folate-R7 NP; folate-R7 nanoparticle; multifunctional nanoparticles; nanoparticle anticancer activity; nanoparticle morphology evaluation; nanoparticle size evaluation; nanoparticle zeta potential evaluation; perifosine co-loaded nanoparticle; perifosine codelivery; perifosine loaded Fol-R7 NP cell uptake; perifosine loaded Fol-R7 NP cytotoxicity; perifosine loaded Fol-R7 NP early apoptosis; phosphoinositide 3-kinase; protein kinase B;

fLanguage

English

Journal_Title

Micro & Nano Letters, IET

Publisher

iet

ISSN

1750-0443

Type

jour

DOI

10.1049/mnl.2014.0661

Filename

7108360