Paclitaxel-loaded poly(D,L-lactide-co-glycolide) nanoparticles for radiotherapy in hypoxic human tumor cells in vitro.
Radioresistant hypoxic cells may contribute to the failure of radiation therapy in controlling certain tumors. Some studies have suggested the radiosensitizing effect of paclitaxel. The poly (D,L-lactide-co-glycolide)(PLGA) nanoparticles containing paclitaxel were prepared by o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e., encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The morphology of the two human tumor cell lines: a carcinoma cervicis (HeLa) and a hepatoma (HepG(2)), treated with paclitaxel-loaded nanoparticles was photomicrographed. Flow cytometry was used to quantify the number of the tumor cells held in the G(2)/M phase of the cell cycle. The cellular uptake of nanoparticles was evaluated by transmission electronic microscopy. Cell viability was determined by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 200 nm and 800 nm. The encapsulation efficiency was 85.5%. The release behaviour of paclitaxel from the nanoparticles exhibited a biphasic pattern characterised by a fast initial release during the first 24 h, followed by a slower and continuous release. Co-culture of the two tumor cell lines with paclitaxel-loaded nanoparticles demonstrated that the cell morphology was changed and the released paclitaxel retained its bioactivity to block cells in the G(2)/M phase. The cellular uptake of nanoparticles was observed. The free paclitaxel and paclitaxel-loaded nanoparticles effectively sensitized hypoxic HeLa and HepG(2) cells to radiation. Under this experimental condition, the radiosensitization of paclitaxel-loaded nanoparticles was more significant than that of free paclitaxel.
Jin
Cheng
C
Department of Radiation Medicine, Fourth Military Medical University, Xi'an, China.
Bai
Ling
L
Wu
Hong
H
Liu
Junye
J
Guo
Guozhen
G
Chen
Jingyuan
J
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002470:Cell Survival; D018920:Coculture Techniques; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011878:Radiotherapy / Q000379:methods*; D012997:Solvents / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel