enhancement of radiotherapeutic efficacy by paclitaxel-loaded ph-sensitive block copolymer micelles
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2012
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Abstract
Radiotherapy (RT) is a major modality for cancer treatment, but its efficacy is often compromised by the resistance caused by tumor-specific microenvironment including acidosis and hypoxia. For an effective RT, concurrent administration of radiosensitizer with RT has been emphasized. However, most anticancer agents enhancing radiotherapeutic efficacy have obstacles such as poor solubility and severe toxicity. Paclitaxel (PTX), a well-known radiosensitizer, is insoluble in water and needs toxic solvent like Cremophor EL. Nanomaterials in drug delivery systems have been utilized for improving the drawbacks of anti-cancer drugs. Solubilization, tumor accumulation, and toxicity attenuation of drug by nanomaterials are suitable for enhancement of radiotherapeutic efficacy. In this study, PTX was incorporated into pH-sensitive block copolymer micelle (psm-PTX), polyethylene glycol-graft-poly(β-amino ester), and preclinically evaluated for its effect on RT. The size of psm-PTX was 125.7±4.4 nm at pH 7.4. psm-PTX released PTX rapidly in the acidic condition (pH 6.5), while it was reasonably stable in the physiologic condition (pH 7.4). The clonogenic assay showed that psm-PTX greatly sensitized human non-small-cell lung cancer A549 cells to radiation. In the xenograft tumor model, the combination of psm-PTX and radiation significantly delayed the tumor growth. These results demonstrated the feasibility of psm-PTX to enhance the chemoradiotherapeutic efficacy.
| Reference Key |
jung2012journalenhancement
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|---|---|
| Authors | ;Joohee Jung;Min Sang Kim;Sung-Jin Park;Hye Kyung Chung;Jinhyang Choi;Jaesook Park;Dong-Hoon Jin;Si Yeol Song;Heon Joo Park;Doo Sung Lee;Seong-Yun Jeong;Eun Kyung Choi |
| Journal | reproductive biology and endocrinology |
| Year | 2012 |
| DOI |
10.1155/2012/867036
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| URL | |
| Keywords |
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