Radiosensitization of paclitaxel, etanidazole and paclitaxel+etanidazole nanoparticles on hypoxic human tumor cells in vitro.
Paclitaxel and etanidazole are hypoxic radiosensitizers that exhibit cytotoxic action at different mechanisms. The poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel, etanidazole and paclitaxel+etanidazole were prepared by o/w and w/o/w emulsification-solvent evaporation method. The morphology of the nanoparticles was investigated by scanning electron microscope (SEM). The drug encapsulation efficiency (EE) and release profile in vitro were measured by high-performance liquid chromatography (HPLC). The cellular uptake of nanoparticles for the human breast carcinoma cells (MCF-7) and the human carcinoma cervicis cells (HeLa) was evaluated by transmission electronic microscopy and fluorescence microscopy. Cell viability was determined by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical shape with size between 80 and 150 nm. The EE was higher for paclitaxel and lower for etanidazole. The drug release was controlled over time. The cellular uptake of nanoparticles was observed. Co-culture of the two tumor cell lines with drug-loaded nanoparticles demonstrated that released drug effectively sensitized hypoxic tumor cells to radiation. The radiosensitization of paclitaxel+etanidazole nanoparticles was more significant than that of single drug-loaded nanoparticles.
Jin
Cheng
C
Department of Radiation Medicine, Fourth Military Medical University, Xi'an 710032, China.
Bai
Ling
L
Wu
Hong
H
Tian
Furong
F
Guo
Guozhen
G
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid; D004307:Dose-Response Relationship, Radiation; D017341:Etanidazole / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D017341:Etanidazole; D019344:Lactic Acid; D017239:Paclitaxel