Polymeric nanoparticles containing taxanes enhance chemoradiotherapeutic efficacy in non-small cell lung cancer.
OBJECTIVE
To reduce the side effects and improve the efficacy of chemoradiation therapy, taxanes were incorporated into polymeric nanoparticles (PNP), and their synergic effect on radiation therapy in non-small cell lung cancer was evaluated.


METHODS
The properties of PNP-taxanes were characterized by transmission electron microscopy and dynamic light scattering. The chemoradiotherapeutic efficacy of PNP-taxanes was determined by clonogenic assay, cellular morphology, and flow cytometry in A549 cells. In mice bearing A549-derived tumors, the tumor growth delay was examined after the treatment of PNP-taxanes and/or ionizing radiation (IR).


RESULTS
The PNP-taxanes were found to be approximately 45 nm in average diameter and to have high solubility in water. They showed the properties of active internalization into cells and preserved the anticancer effect of free taxanes. The survival fraction of A549 cells by clonogenic assay was significantly reduced in the group receiving combined treatment of PNP-taxanes and IR. In addition, in vivo radiotherapeutic efficacy was markedly enhanced by the intravenous injection of PNP-taxanes into the xenograft mice.


CONCLUSIONS
We have demonstrated the feasibility of PNP-taxanes to enhance the efficacy of chemoradiation therapy. These results suggest PNP-taxanes can hold an invaluable and promising position in treating human cancers as a novel and effective chemoradiation therapy agent.
Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Joohee
J
Jung
Sung-Jin
SJ
Park
Hye Kyung
HK
Chung
Hye-Won
HW
Kang
Sa-Won
SW
Lee
Min Hyo
MH
Seo
Heon Joo
HJ
Park
Si Yeol
SY
Song
Seong-Yun
SY
Jeong
Eun Kyung
EK
Choi
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D000077143:Docetaxel; D004357:Drug Synergism; D004705:Endocytosis; D005240:Feasibility Studies; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D058726:Nanoconjugates / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D017239:Paclitaxel / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011897:Random Allocation; D043823:Taxoids / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000972:Antineoplastic Agents, Phytogenic; D058726:Nanoconjugates; D011108:Polymers; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel