Evaluation of the Effect of Resveratrol and Doxorubicin on 99mTc-MIBI Uptake in Breast Cancer Cell Xenografts in Mice.

BACKGROUND AND OBJECTIVE: Doxorubicin (DOX), despite having antitumor properties, also exhibits cardiotoxicity. Resveratrol has antitumor property for breast cancer cells. 99mTc-MIBI has higher absorption rate in human breast cancer cell line MCF-7. In the present study, the authors intend to investigate the effect of DOX and resveratrol on the absorption of 99mTc-MIBI in breast cancer cell xenografts in mice. MATERIALS AND METHODS: Sixteen xenograft models in nude mice were divided into four groups. Group I (S, control) received 2% DMSO in 0.9% saline, group II (D) 2.5 mg/kg DOX, group III (D + R) 20 mg/kg/d resveratrol with 2.5 mg/kg DOX (total dose of 15 mg/kg in six injections), and group IV (R) 20 mg/kg/d resveratrol for 2 weeks. Single-photon emission computed tomography (SPECT) images were taken for the determination of 99mTc-MIBI absorption. Mice were sacrificed, and the percentage of injected dose per gram (%ID/g) of the heart, liver, tumor, and muscle was measured using a gamma counter. Hematoxylin-eosin staining and Masson's trichrome staining were used for investigation of histopathological changes. RESULTS: The %ID/g of tumor was lowest in group D + R. The severity of tumor necrosis or apoptosis was highest in group D + R, but there is no significant difference in pathological injuries and %ID/g of tumor between the group D + R and group D. In addition to the results of the %ID/g, the severity of pathological injuries to the liver and heart cells in group D + R was higher compared with group D. There is a significant difference in the %ID/g of the liver between the group D + R and group D. SPECT images showed that the lowest amount of %ID/g was observed in the tumor of group D + R. CONCLUSIONS: According to the results of pathology, biodistribution study, and imaging, the combination of DOX and resveratrol has shown higher antitumor effect; hence, 99mTc-MIBI can be used to evaluate their antitumor effect.

Pharmacokinetics and in vitro/in vivo antitumor efficacy of aptamer-targeted Ecoflex® nanoparticles for docetaxel delivery in ovarian cancer.

PURPOSE: Epithelixal ovarian cancer is the fourth cause of cancer death in developed countries with 77% of ovarian cancer cases diagnosed with regional or distant metastasis, with poor survival rates. Docetaxel (DTX) is a well-known anticancer agent, with clinically proven efficacy in several malignancies, including ovarian cancer. However, the adverse effects caused by the active ingredient or currently marketed formulations could even deprive the patient of the advantages of treatment. Therefore, in the current study, polymeric nanoparticles (NPs) equipped with aptamer molecules as targeting agents were proposed to minimize the adverse effects and enhance the antitumor efficacy through directing the drug cargo toward its site of action. MATERIALS AND METHODS: Electrospraying technique was implemented to fabricate poly (butylene adipate-co-butylene terephthalate) (Ecoflex®) NPs loaded with DTX (DTX-NPs). Afterward, aptamer molecules were added to the DTX-NPs, which bound via covalent bonds (Apt-DTX-NPs). The particle size, size distribution, zeta potential, entrapment efficiency, and release profile of the NPs were characterized. Using MTT assay and flow-cytometry analysis, the in vitro cytotoxicity and cellular uptake of the NPs were compared to those of the free drug. Following intravenous administration of Taxotere®, DTX-NPs, and Apt-DTX-NPs (at an equivalent dose of 5 mg/kg of DTX), pharmacokinetic parameters and antitumor efficacy were compared in female Balb/c and HER-2-overexpressing tumor-bearing B6 athymic mice, respectively. RESULTS: The obtained results demonstrated significantly enhanced in vitro cytotoxicity and cellular uptake of Apt-DTX-NPs in a HER-2-overexpressing cell line, comparing to DTX-NPs and the free drug. The results of in vivo studies indicated significant increment in pharmacokinetic parameters including the area under the plasma concentration-time curve, mean residence time, and elimination half-life. Significant increment in antitumor efficacy was also observed, probably due to the targeted delivery of DTX to the tumor site and enhanced cellular uptake as evaluated in the aforementioned tests. CONCLUSION: Hence, the proposed drug delivery system could be considered as an appropriate potential substitute for currently marketed DTX formulations.