Cellular Uptake and Antitumor Activity of DOX-hyd-PEG-FA Nanoparticles | Zendy

Weiliang Ye | Zendy; Jiangbo Du | Zendy; BangLe Zhang | Zendy; Ren Na | Zendy; Yanfeng Song | Zendy; Qibing Mei | Zendy; Ming Zhao | Zendy; Siyuan Zhou | Zendy

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Cellular Uptake and Antitumor Activity of DOX-hyd-PEG-FA Nanoparticles

Author(s) -

Weiliang Ye,

Jiangbo Du,

BangLe Zhang,

Ren Na,

Yanfeng Song,

Qibing Mei,

Ming Zhao,

Siyuan Zhou

Publication year - 2014

Publication title -

plos one

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.99

H-Index - 332

ISSN - 1932-6203

DOI - 10.1371/journal.pone.0097358

Subject(s) - peg ratio , cytotoxicity , doxorubicin , chemistry , drug delivery , pharmacology , cardiotoxicity , folate receptor , targeted drug delivery , ic50 , cancer cell , biochemistry , in vitro , toxicity , chemotherapy , cancer , medicine , surgery , organic chemistry , finance , economics

A PEG-based, folate mediated, active tumor targeting drug delivery system using DOX-hyd-PEG-FA nanoparticles (NPs) were prepared. DOX-hyd-PEG-FA NPs showed a significantly faster DOX release in pH 5.0 medium than in pH 7.4 medium. Compared with DOX-hyd-PEG NPs, DOX-hyd-PEG-FA NPs increased the intracellular accumulation of DOX and showed a DOX translocation from lysosomes to nucleus. The cytotoxicity of DOX-hyd-PEG-FA NPs on KB cells was much higher than that of free DOX, DOX-ami-PEG-FA NPs and DOX-hyd-PEG NPs. The cytotoxicity of DOX-hyd-PEG-FA NPs on KB cells was attenuated in the presence of exogenous folic acid. The IC 50 of DOX-hyd-PEG-FA NPs and DOX-hyd-PEG NPs on A549 cells showed no significant difference. After DOX-hyd-PEG-FA NPs were intravenously administered, the amount of DOX distributed in tumor tissue was significantly increased, while the amount of DOX distributed in heart was greatly decreased as compared with free DOX. Compared with free DOX, NPs yielded improved survival rate, prolonged life span, delayed tumor growth and reduced the cardiotoxicity in tumor bearing mice model. These results indicated that the acid sensitivity, passive and active tumor targeting abilities were likely to act synergistically to enhance the drug delivery efficiency of DOX-hyd-PEG-FA NPs. Therefore, DOX-hyd-PEG-FA NPs are a promising drug delivery system for targeted cancer therapy.

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