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ORIGINAL ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 4  |  Page : 979-984

Sanazole directed targeting of silver nanoparticle drug complex to tumor mass: A preclinical investigation in murine model


1 Department of Radiation Biology, Amala Cancer Research Centre, Thrissur, India
2 Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla, Kerala, India

Correspondence Address:
Cherupally Krishnan Krishnan Nair
Dean of Research, Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla - 689 101, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.148705

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Aim of Study: To explore sanazole (AK) directed targeting of the antineoplastic drug doxorubicin (DOX) complexed with silver nanoparticles (SNs) to tumor growth in a murine model. Materials and Methods: Sanazole (AK) and DOX were complexed with SNs, individually and in combination to obtain SN-AK, SN-DOX, and SN-AK-DOX. Solid tumors were developed on hind limbs of Swiss albino mice by transplanting Dalton's lymphoma ascitess (DLAs) tumor cells. Induction of cytotoxicity and apoptosis in the DLA cells by AK and DOX complexed with SN, individually and in combination, were examined under in vitro conditions by incubating the cells with them. SN, AK, DOX, SN-AK, SN-DOX, AK-DOX, and SN-AK-DOX were administered orally to the tumor bearing mice and the therapeutic efficacy of AK-directed targeting of SN-DOX complexes to achieve tumor control was monitored. Results: Under in vitro conditions, SN, AK, DOX, SN-AK, SN-DOX, AK-DOX, and SN-AK-DOX induced cytotoxicity and apoptosis in DLA cells to varying extents. The SN-AK-DOX complex showed higher level of cytotoxicity and apoptosis-induction in DLA cells. Similarly, administration of SN, AK, DOX, SN-AK, SN-DOX, AK-DOX, and SN-AK-DOX resulted in significant reduction in tumor volume and delay in tumor growth. The animals treated with SN-AK-DOX had the highest reduction in tumor volume and tumor growth. In fact, the tumor was almost absent in the animals of this group after the treatment. Conclusion: The SN complex of sanazole and doxorubicin together (SN-AK-DOX) has high anticancer activity under in vivo conditions and has great potential in tumor therapy.

Abstract in Chinese

沙纳唑靶向引导纳米银药物复合物作用于肿瘤:小鼠模型的临床前研究 摘要 研究目的:探讨沙纳唑(AK)靶向引导抗肿瘤药物阿霉素(DOX)纳米银粒子(SNs)复合物作用于鼠科模型中肿瘤的生长。 材料与方法:将沙纳唑(AK)、阿霉素(DOX)单体及合成物分别与纳米银(SNs)合成,获得SN-AK、SN-DOX和SN-AK-DOX。实体瘤是通过在瑞士白化小鼠后肢移植达尔顿淋巴瘤腹水(DLAS)肿瘤细胞而培育。在体外条件下培育DLA细胞,分别单独加入AK、DOX及SN或它们的复合物,检查细胞毒性和诱导凋亡作用。SN、 AK、DOX、SN-AK、SN-DOX、AK-DOX及 SN-AK-DOX通过口服给药于肿瘤小鼠,对AK靶向引导的SN-DOX复合物控制肿瘤的治疗效果进行监测。 结果:在体外条件下,SN、AK、DOX、SN-AK、SN-DOX、AK-DOX 及 SN-AK-DOX诱导的细胞毒性和细胞凋亡表现出不同的程度。SN-AK-DOX复合体在DLA细胞中表现出更高的细胞毒性和细胞凋亡的诱导能力。同样,SN、AK、DOX、SN-AK、SN-DOX、AK-DOX及 SN-AK-DOX的注入明显导致肿瘤体积的减少和肿瘤生长的延迟。SN-AK-DOX治疗的动物最大地减少了肿瘤体积,延缓了肿瘤生长。事实上,这一组动物的肿瘤在治疗后几乎都消失了。 结论:阿霉素的沙纳唑纳米银复合物(SN-AK-DOX)在体内具有很高的抗癌活性,在肿瘤治疗中具有很大的潜力。 关键词:抗肿瘤活性,DLA细胞,阿霉素,靶向药物,沙纳唑,纳米银



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