In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 2644-2644
Abstract:
Recently drug delivery systems are focusing on the improvement of efficacy, the reduction of side effect, and diagnostics. In the current research, we developed a novel polymeric nanoparticle (YCC) with anticancer effect as well as magnetic resonance (MR) imaging, which encapsulate doxorubicin and superparamagnetic iron oxide (Fe3O4) with the size of 86.4 nm. The efficacy of the nanoparticles was evaluated in hepatocellular carcinoma (HCC) rats induced by the treatment of diethylnitrosamine for 13 weeks as well as in rabbit model with VX2 carcinoma in the liver, comparing with free doxorubicin (FD) and a commercial liposome drug DOXIL®. Each formula was administered intravenously at a dose of 2 mg/kg as doxorubicin three times with 5 day intervals, and anticancer efficacy of YCC were confirmed by MRI (T2) and hematoxylin-eosin (H & E) staining. The tumor size using MRI and the change of body weight were monitored for 10 days after the last administration of each formula. On the end of the study (Day 20th), all the formulas containing doxorubicin suppressed the tumor growth compared with the saline-treated group (control). Especially the relative tumor volume of YCC group was decreased three and four fold compared with the FD and DOXIL® group, respectively. Nevertheless, the loss of body weight as a side effect in YCC group was lower than FD or DOXIL® group. The results from Perls staining and transmission electron microscopy (TEM) confirmed that YCC was distributed in the liver, especially in tumor region rather than non-tumor region. In rabbit model with VX2 carcinoma in the liver, the relative tumor volume in YCC group was decreased two and four fold compared with the FD and DOXIL® group, respectively, as a result of MRI and tissue staining. Like in rat model, the loss of body weight as a side effect in YCC group was lower than FD or DOXIL® group. In both rat and rabbit model, YCC showed the MRI sensitivity comparable to a conventional MRI contrast agent (Resovist®) even in its lower iron content. In the immunohistochemical analysis, YCC group showed the lower expression of CD34 and Ki-67, markers of angiogenesis and cell proliferation, respectively, while apoptotic cells were significantly rich in the YCC group in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Taken together, a novel nanoparticle YCC had anticancer efficacy better than conventional doxorubicin formulas (free doxorubicin and DOXIL®) with the function of MR imaging in rat and rabbit model with carcinoma in the liver. It was considered to a good candidate for the treatment of liver cancer monitoring the progress of the cancer using MRI. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2644.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-2644
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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