圖1：鐵蛋白納米載體靶向輸送抗癌藥物(A)鐵蛋白納米載體裝載抗癌藥物;(B)攜帶抗癌藥物的鐵蛋白納米粒精確靶向腫瘤;(C)裝載抗癌藥物的鐵蛋白納米粒有效治療結(jié)腸癌，延長(zhǎng)生存期。

化療是當(dāng)前癌癥病人首選的治療方式，然而化療中存在的主要問(wèn)題是毒副作用大。如何提高藥物的療效、降低其副作用，一直是腫瘤藥物研究的關(guān)鍵和難題。隨著納米科學(xué)的蓬勃發(fā)展，利用納米技術(shù)改良藥物的性狀，使其精準(zhǔn)地殺傷腫瘤細(xì)胞，減少對(duì)正常組織的損傷，是腫瘤靶向治療的核心。為了獲得具有主動(dòng)靶向功能的藥物載體，人們通常在納米材料的表面修飾一些功能基團(tuán)，如特異識(shí)別腫瘤的抗體等。然而，修飾過(guò)程不僅復(fù)雜、成本高、而且修飾后的載體分子容易聚集，造成產(chǎn)品不均一。另外，納米材料的生物相容性差也是引起免疫系統(tǒng)識(shí)別和清除的重要原因。

閻錫蘊(yùn)課題組依據(jù)人體天然鐵蛋白獨(dú)特的殼核結(jié)構(gòu)，仿生合成了24 聚體鐵蛋白納米粒子，其外殼直徑12nm，內(nèi)腔為8nm能有效裝載化療藥物阿霉素。鐵蛋白納米載體有3個(gè)突出的特點(diǎn)：(1)由人體天然蛋白質(zhì)自組裝而成的藥物載體;(2)無(wú)需在其表面做任何修飾，即可直接識(shí)別并殺傷腫瘤;(2)動(dòng)物實(shí)驗(yàn)結(jié)果表明，單劑量給藥就能有效抑制結(jié)腸癌、乳腺癌及黑色素瘤的生長(zhǎng)。與目前國(guó)際上唯一應(yīng)用于臨床的脂質(zhì)體阿霉素納米藥物相比，療效更好、存活率長(zhǎng)而且毒副作用小。

這種新型藥物載體不僅能夠在腫瘤組織富集，而且還使腫瘤細(xì)胞內(nèi)的藥物濃度提高十倍，使阿霉素所致的心臟毒性降低七倍。進(jìn)一步機(jī)制研究發(fā)現(xiàn)，鐵蛋白載體結(jié)合腫瘤細(xì)胞膜上的轉(zhuǎn)鐵蛋白受體，是其靶向腫瘤的分子基礎(chǔ)。另外，鐵蛋白納米粒子作為天然蛋白質(zhì)，生物相容性好，不易引起機(jī)體的免疫排斥反應(yīng)，因此毒性小。本文為天然蛋白納米粒作為高效低毒的靶向載體的研究提供了新思路。

原文摘要：

H-ferritin–nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection

Minmin Liang, Kelong Fan, Meng Zhou, Demin Duan, Jiyan Zheng, Dongling Yang, Jing Feng and Xiyun Yan

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.

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干細(xì)胞治療所用的無(wú)血清培養(yǎng)基 lonza 12-725F無(wú)血清培養(yǎng)基  （點(diǎn)擊進(jìn)入）

lonza 無(wú)血清培養(yǎng)基  （點(diǎn)擊進(jìn)入）

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