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用于癌症治疗的二嵌段共聚物胶束包封姜黄素

Encapsulation of curcumin in diblock copolymer micelles for cancer therapy.

作者信息

Alizadeh Ali Mohammad, Sadeghizadeh Majid, Najafi Farhood, Ardestani Sussan K, Erfani-Moghadam Vahid, Khaniki Mahmood, Rezaei Arezou, Zamani Mina, Khodayari Saeed, Khodayari Hamid, Mohagheghi Mohammad Ali

机构信息

Cancer Research Center, Tehran University of Medical Sciences, Tehran 14197-33141, Iran.

Department of Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran 14115-137, Iran.

出版信息

Biomed Res Int. 2015;2015:824746. doi: 10.1155/2015/824746. Epub 2015 Feb 22.

Abstract

Application of nanoparticles has recently promising results for water insoluble agents like curcumin. In this study, we synthesized polymeric nanoparticle-curcumin (PNPC) and then showed its efficiency, drug loading, stability, and safety. Therapeutic effects of PNPC were also assessed on two cell lines and in an animal model of breast cancer. PNPC remarkably suppressed mammary and hepatocellular carcinoma cells proliferation (P < 0.05). Under the dosing procedure, PNPC was safe at 31.25 mg/kg and lower doses. Higher doses demonstrated minimal hepatocellular and renal toxicity in paraclinical and histopathological examinations. Tumor take rate in PNPC-treated group was 37.5% compared with 87.5% in control (P < 0.05). Average tumor size and weight were significantly lower in PNPC group than control (P < 0.05). PNPC increased proapoptotic Bax protein expression (P < 0.05). Antiapoptotic Bcl-2 protein expression, however, was lower in PNPC-treated animals than the control ones (P < 0.05). In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P < 0.05). These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models. Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response.

摘要

纳米颗粒的应用最近在姜黄素等水不溶性药物方面取得了有前景的成果。在本研究中,我们合成了聚合物纳米颗粒 - 姜黄素(PNPC),然后展示了其有效性、载药量、稳定性和安全性。还在两种细胞系和乳腺癌动物模型中评估了PNPC的治疗效果。PNPC显著抑制了乳腺癌细胞和肝癌细胞的增殖(P < 0.05)。在给药过程中,PNPC在31.25 mg/kg及更低剂量时是安全的。更高剂量在临床前和组织病理学检查中显示出最小的肝细胞和肾毒性。PNPC治疗组的肿瘤发生率为37.5%,而对照组为87.5%(P < 0.05)。PNPC组的平均肿瘤大小和重量显著低于对照组(P < 0.05)。PNPC增加了促凋亡蛋白Bax的表达(P < 0.05)。然而,PNPC治疗动物的抗凋亡蛋白Bcl-2表达低于对照组(P < 0.05)。此外,PNPC治疗动物的增殖和血管生成参数在统计学上有所降低(P < 0.05)。这些结果突出了PNPC在体外和体内肿瘤生长模型中的抑制作用。我们的研究结果为聚合物纳米载体在药理学领域的卓越生物相容性以及出色的肿瘤抑制反应提供了可靠证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/255c/4352453/fdc94cbfbe82/BMRI2015-824746.001.jpg

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