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H-ferritin–nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection, PNAS, September 29, 2014

发布时间:2014年10月08日

PNAS, Published online before print September 29, 2014, doi: 10.1073/pnas.1407808111
H-ferritin–nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection

Minmin Lianga,1, Kelong Fana,b,1, Meng Zhoua,b, Demin Duana, Jiyan Zhenga, Dongling Yanga, Jing Fenga, and Xiyun Yana,2

Significance

Nanoparticles capable of specifically binding to target cells and delivering high doses of therapeutic drugs with optimized safety profiles are much sought after in the nanomedical field. Here, we developed a natural H-ferritin (HFn) nanocarrier that specifically delivered a high concentration of the therapeutic drug doxorubicin (Dox) to tumor cells and significantly inhibited tumor growth with a single-dose treatment while also showing excellent biocompatibility and safety profiles in murine cancer models. Compared with the clinically approved liposomal Dox (Doxil), HFn-Dox exhibited longer median survival times and lower toxicity when administered at the same dose in all tumor models studied.

Abstract

An ideal nanocarrier for efficient drug delivery must be able to target specific cells and carry high doses of therapeutic drugs and should also exhibit optimized physicochemical properties and biocompatibility. However, it is a tremendous challenge to engineer all of the above characteristics into a single carrier particle. Here, we show that natural H-ferritin (HFn) nanocages can carry high doses of doxorubicin (Dox) for tumor-specific targeting and killing without any targeting ligand functionalization or property modulation. Dox-loaded HFn (HFn-Dox) specifically bound and subsequently internalized into tumor cells via interaction with overexpressed transferrin receptor 1 and released Dox in the lysosomes. In vivo in the mouse, HFn-Dox exhibited more than 10-fold higher intratumoral drug concentration than free Dox and significantly inhibited tumor growth after a single-dose injection. Importantly, HFn-Dox displayed an excellent safety profile that significantly reduced healthy organ drug exposure and improved the maximum tolerated dose by fourfold compared with free Dox. Moreover, because the HFn nanocarrier has well-defined morphology and does not need any ligand modification or property modulation it can be easily produced with high purity and yield, which are requirements for drugs used in clinical trials. Thus, these unique properties make the HFn nanocage an ideal vehicle for efficient anticancer drug delivery.

相关报道: http://www.ibp.cas.cn/kyjz/zxdt/201410/t20141002_4219072.html

文章链接: http://www.pnas.org/content/early/2014/09/24/1407808111.abstract?sid=49f17b42-abfa-421e-a59a-f737be8d46c3

 

 

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