The performance of thiol-terminated PEG-paclitaxel-conjugated gold nanoparticles.
A series of thiol-terminated polyethylene glycol (PEG)-paclitaxel (PTX) derivatives are designed and synthesized to fabricate PTX-conjugated gold nanoparticles (PTX@GNPs) and improve their overall performance. By extending the molecular weight of PEG from 400 to 1000 Da, the optimized water solubility of the conjugate reaches 184 mg/mL, equal to 4.6 × 10(5) times that of PTX alone (0.4 μg/mL). High drug loading is obtained by eliminating the steric hindrance between PTX molecules on the surface of GNPs. The gold conjugate shows double simultaneous stimulation-induced drug release behavior in the presence of both esterase and high concentrations of glutathione. The synergic release characteristics of this conjugate results in significant performance improvements, including prolonged circulation due to high stability in vivo, targeted release of PTX inside tumor cells, and increased tumor cell killing efficiency. Improving the in vitro properties of the conjugate not only significantly enhances its therapeutic efficacy in a murine liver cancer model, but also allows drug-conjugated gold nanoparticles to be used as a promising nanoprodrug system in the cancer therapeutics.
Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009, China. Electronic address: ayanju@163.com.
Ya
Y
Ding
Ying-Ying
YY
Zhou
Huan
H
Chen
Dong-Dong
DD
Geng
Dong-Yan
DY
Wu
Jin
J
Hong
Wen-Bin
WB
Shen
Tai-Jun
TJ
Hang
Can
C
Zhang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use; D006046:Gold / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D017239:Paclitaxel / Q000737:chemistry* / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D011092:Polyethylene Glycols; D006046:Gold; D017239:Paclitaxel
Double simultaneous stimulation; Drug release; Overall performance improvement; Paclitaxel-conjugated gold nanoparticles; Target selection; Tumor therapeutic efficacy