Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells.
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 ~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.
College of Pharmacy, Yeungnam University, Dae-Dong, South Korea.
Tuan Hiep
TH
Tran
College of Pharmacy, Yeungnam University, Dae-Dong, South Korea.
Thiruganesh
T
Ramasamy
College of Pharmacy, Yeungnam University, Dae-Dong, South Korea.
Ju Yeon
JY
Choi
College of Pharmacy, Yeungnam University, Dae-Dong, South Korea.
Hanh Thuy
HT
Nguyen
College of Pharmacy, Yeungnam University, Dae-Dong, South Korea.
Thanh Tung
TT
Pham
College of Pharmacy, Yeungnam University, Dae-Dong, South Korea.
Jee-Heon
JH
Jeong
College of Korean Medicine, Daegu Haany University, Gyeongsan, South Korea.
Sae Kwang
SK
Ku
College of Pharmacy, Hanyang University, Hanyangdaehak-ro, Sangnok-gu, Ansan, South Korea.
Han-Gon
HG
Choi
College of Pharmacy, Yeungnam University, Dae-Dong, South Korea.
Chul Soon
CS
Yong
College of Pharmacy, Yeungnam University, Dae-Dong, South Korea.
Jong Oh
JO
Kim
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D000077143:Docetaxel; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D004655:Emulsions / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000494:pharmacology; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles; D010316:Particle Size; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004655:Emulsions; D008055:Lipids; D008823:Micelles; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3
antitumor; docetaxel; drug delivery systems; pH-sensitive; polyaspartic acid