[논문]Intratumoral Administration of Rhenium-188-Labeled Pullulan Acetate Nanoparticles (PAN) in Mice Bearing CT-26 Cancer Cells for Suppression of Tumor Growth

Song, Ho-Chun; Na, Kun; Park, Keun-Hong; Shin, Chan-Ho; Bom, Hee-Seung; Kang, Dong-Min; Kim, Sung-Won; Lee, Eun-Seong; Lee, Don-Haeng

Intratumoral Administration of Rhenium-188-Labeled Pullulan Acetate Nanoparticles (PAN) in Mice Bearing CT-26 Cancer Cells for Suppression of Tumor Growth 원문보기

Journal of microbiology and biotechnology, v.16 no.10, 2006년, pp.1491 - 1498

Song, Ho-Chun (Department of Nuclear Medicine, Chonnam National University Hospital) , Na, Kun (Division of Biotechnology, The Catholic University of Korea) , Park, Keun-Hong (College of Medicine, Pochon CHA University, Cell and Gene Therapy Research Institute) , Shin, Chan-Ho (Department of Nuclear Medicine, Chonnam National University Hospital) , Bom, Hee-Seung (Department of Nuclear Medicine, Chonnam National University Hospital) , Kang, Dong-Min (Korea Basic Science Institute, Chuncheon Center) , Kim, Sung-Won (Biomedical Research Center, Korea Institute of Science and Technology) , Lee, Eun-Seong (Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah) , Lee, Don-Haeng (Department of Internal Medicine, Inha University)

Abstract ▼ AI-Helper

The feasibility of pullulan acetate nanoparticles (PAN) with ionic strength (IS) sensitivity as a radioisotope carrier to inhibit tumor growth is demonstrated. PAN was radiolabeled with rhenium 188 (Re-188) without any chelating agents. The labeling efficiency of Re-188 into PAN (Re-188PAN) was $49.3{\pm}4.0%$ as determined by TLC. The tumor volumes of mice treated with 0.45 mCi of Re-188-PAN were measured and compared with that of free Re-188 after 5 days of intratumoral injection. For the histological evaluation of apoptotic nuclei of tumor cells, hematoxylin and eosin (H&E), and terminal deoxynucleotidyl transferase biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) staining were performed. The mean tumor volume of the Re-188-PAN-treated group was decreased by 36% after 5 days, whereas that the free Re-188-treated group was decreased by only 15% (P<0.05). The mean number of TUNEL-positive cells in Re-188-PAN-treated tumors at $144.3{\pm}79.9$ cells/section was significantly greater than the control ($26.7{\pm}7.9$ cells/section, P=0.03). The numbers of leukocyte and lymphocyte were decreased in both free Re-188- and Re-188-PAN-treated mice. These results indicated that the intratumoral injection of Re-188-PAN effectively inhibits the tumor growth by prolonging Re-188 retention time in tumor site induced by the IS sensitivity.

주제어

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문제 정의

of a radioisotope in the target site and organ. In this paper, we biggest a new concept for the intratumoral delivery of radioisotopes using a self-assembled nanoparticle with ionic strength (IS)-sensitivity in the body condition. The IS-sensitive nanoparticles might exist as a stable state in distilled water (D.
The purpose of this study was to develop a stimuli sensitive nanoparticle for an effective radiotherapy of solid tumor. The carrier with a radioisotope was expected to stay in the tumor mass when injected directly into the tumor, because the carrier might be aggregated inside the tumor (IS=0.

제안 방법

1 ml of the tumor cell [murine colon adenocarcinoma cell line (CT-26)] suspension (2x 107 cells) was injected subcutaneously into the back of the Balb/c mice. All mice were carefully observed daily, and body weights were measured at the start and end of experiments. Tumor volumes were measured daily for 5 days with a digimatic caliper (Mitutoyo Corp.
2). To observe the IS-sensitivity of PAN prepared in D.W. (IS=0.0), aggregation behavior was studied by examining the turbidity according to time course (Fig. 3). When PAN solution was added into the sol니tions with various ISs, the turbidity of all samples dropped dramatically in just 6 min, except in the case of D.

대상 데이터

Japan). Acetic anhydride, formamide, dimethyl sulfoxide (DMSO), acetone, and pyridine were purchased from Sigma-Aldrich Co. (St. Louis, MI, U.S.A.). Pullulan was purified by a protocol including filtration (0.

데이터처리

Descriptive data are presented as mean士standard deviation. Continuous variables, tumor volumes, apoptotic cells, and hematological parameters of three groups (PAN-, free Re- 188-, and Re-188-PAN-treated groups) were compared using the ANOVA test. The difference was considered to be significant if the p value was less than 0.

이론/모형

Nanoparticles were prepared by a dialysis method (molecular cutoff 2,000). PA (50 mg) was diss이ved in 20 ml of dimethyl sulfoxide (DMSO), and the solution was stirred at room temperature and dialyzed against distilled water for 3 days.

성능/효과

In conclusion, we observed that the IS-dependent PAN was successfully retained with carrying radioisotope in the tumor sites. Moreover, intratumoral injection of PAN labeled with beta-emitting Re-188 effectively inhibited the tumor growth.

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