Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells

Title
Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells
Author(s)
김종오트란탄힙티르거네쉬라마사미최주연응웬한투이팜탄텅정지헌구세광[구세광]최한곤[최한곤]용철순
Keywords
SOLID LIPID NANOPARTICLES; POLYMER HYBRID NANOPARTICLES; ANTICANCER DRUG; CO-DELIVERY; IN-VITRO; CATIONIC NANOPARTICLES; ANTITUMOR EFFICACY; INHIBITOR P27; BREAST-CANCER; THERAPY
Issue Date
201508
Publisher
DOVE MEDICAL PRESS LTD
Citation
INTERNATIONAL JOURNAL OF NANOMEDICINE, v.10, pp.5249 - 5262
Abstract
The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH) nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX) was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol-b-polyaspartic acid (PEG-b-PAsp) using a modified emulsion method. The optimized LPH nanoparticles were similar to 200 nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH) nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment. Thus, the results suggest that this novel LPH system could be an effective new treatment for cancer.
URI
http://hdl.handle.net/YU.REPOSITORY/31453http://dx.doi.org/10.2147/IJN.S89584
ISSN
1178-2013
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약학대학 > 약학부 > Articles
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