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丹酚酸B可保护免受纳米载体TiO₂所致的心肌损伤；并通过叶酸靶向和聚乙二醇修饰的TiO₂纳米颗粒共递送系统与姜黄素产生协同抗乳腺癌作用。

Salvianolic acid B protects against myocardial damage caused by nanocarrier TiO; and synergistic anti-breast carcinoma effect with curcumin via codelivery system of folic acid-targeted and polyethylene glycol-modified TiO nanoparticles.

作者信息

Ding Lingling, Li Jiawei, Huang Rui, Liu Zhidong, Li Chunhua, Yao Shaozi, Wang Jinyan, Qi Dongli, Li Nan, Pi Jiaxin

机构信息

Tianjin State Key Laboratory of Modern Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine; Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Tianjin University of Traditional Chinese Medicine; Tianjin International Joint Academy of Biomedicine, Tianjin, People's Republic of China.

Tianjin State Key Laboratory of Modern Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine; Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Tianjin University of Traditional Chinese Medicine.

出版信息

Int J Nanomedicine. 2016 Nov 2;11:5709-5727. doi: 10.2147/IJN.S107767. eCollection 2016.

DOI:10.2147/IJN.S107767
PMID:27843313
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5098748/
Abstract

Targeted delivery by the folate ligand is an effective way to enhance an anti-breast carcinoma effect, due to its high affinity for the folate receptor, which is overexpressed in many tumor cells. In this study, we firstly synthesized a folic acid (FA)-targeted and polyethylene glycol (PEG)-modified TiO nanocarrier. Then, an FA-PEG-TiO nanoparticle (NP) codelivery system loaded with curcumin and salvianolic acid B were prepared by emulsion evaporation-solidification at low temperature. The obtained folate-targeted NPs (FA-NPs) showed more cytotoxicity on MCF7 cells and MDA-MB-231 cells than a nontargeted NP group. Apart from a synergistic anti-breast cancer effect with curcumin, salvianolic acid B protects the cardiovascular system from oxidative injury by the TiO nanocarrier. With coumarin 6 as a fluorescent probe to observe cellular uptake of NPs, the results of in vitro cellular uptake demonstrated FA-NPs exhibited higher cellular uptake and accumulation in MCF7 cells and MDA-MB-231 cells than nontargeted NPs. Then, in vivo biodistribution of NPs was further qualitatively and quantitatively confirmed by in vivo imaging. More importantly, the animal study further suggested that FA-NPs had significantly stronger antitumor effects via receptor-mediated targeted delivery. Consequently, FA-PEG-TiO NPs loaded with curcumin and salvianolic acid B could be a promising drug-delivery system to treat breast cancer.

摘要

由于叶酸配体对叶酸受体具有高亲和力，而叶酸受体在许多肿瘤细胞中过表达，因此通过叶酸配体进行靶向递送是增强抗乳腺癌效果的有效方法。在本研究中，我们首先合成了一种叶酸（FA）靶向且聚乙二醇（PEG）修饰的TiO纳米载体。然后，通过低温乳液蒸发-固化法制备了负载姜黄素和丹酚酸B的FA-PEG-TiO纳米颗粒（NP）共递送系统。所获得的叶酸靶向纳米颗粒（FA-NPs）对MCF7细胞和MDA-MB-231细胞的细胞毒性比非靶向NP组更强。除了与姜黄素具有协同抗乳腺癌作用外，丹酚酸B还可通过TiO纳米载体保护心血管系统免受氧化损伤。以香豆素6作为荧光探针观察纳米颗粒的细胞摄取情况，体外细胞摄取结果表明，FA-NPs在MCF7细胞和MDA-MB-231细胞中的细胞摄取和积累高于非靶向纳米颗粒。然后，通过体内成像进一步定性和定量地证实了纳米颗粒在体内的生物分布。更重要的是，动物研究进一步表明，FA-NPs通过受体介导的靶向递送具有显著更强的抗肿瘤作用。因此，负载姜黄素和丹酚酸B的FA-PEG-TiO纳米颗粒可能是一种有前景的治疗乳腺癌的药物递送系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/5cea532a0212/ijn-11-5709Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/e6a31fd42586/ijn-11-5709Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/b0d22e159242/ijn-11-5709Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/e2e4e24cb381/ijn-11-5709Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/0efe1ada8a17/ijn-11-5709Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/c185eae70ae1/ijn-11-5709Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/c93a25c627ce/ijn-11-5709Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/852524dbc214/ijn-11-5709Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/346f5b028668/ijn-11-5709Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/5cea532a0212/ijn-11-5709Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/e6a31fd42586/ijn-11-5709Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/b0d22e159242/ijn-11-5709Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/e2e4e24cb381/ijn-11-5709Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/0efe1ada8a17/ijn-11-5709Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/c185eae70ae1/ijn-11-5709Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/c93a25c627ce/ijn-11-5709Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/852524dbc214/ijn-11-5709Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/346f5b028668/ijn-11-5709Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cc/5098748/5cea532a0212/ijn-11-5709Fig9.jpg

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本文引用的文献

[1]
Hydrothermal synthesis of titanium dioxide nanoparticles: mosquitocidal potential and anticancer activity on human breast cancer cells (MCF-7).

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