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7月3日，德國(guó)《應(yīng)用化學(xué)》雜志刊出新聞稿（Press Release），以題目為“印跡球抗擊乳腺癌：分子印跡納米顆粒抑制腫瘤細(xì)胞表面人表皮生長(zhǎng)因子受體2”（Imprinted Spheres Fight Breast Cancer: Inhibition of HER2 on tumor cells by molecularly imprinted nanoparticles）專題向公眾介紹了我院劉震教授在該刊發(fā)表的最新論文（Zhen Liu, et al. Inhibition of HER2-Positive Breast Cancer Growth by Blocking the HER2 Signaling Pathway with HER2-Glycan-Imprinted Nanoparticles. Angewandte Chemie International Edition, 2019, 10.1002/anie.201904860）。此前，該論文已被《應(yīng)用化學(xué)》雜志選為熱點(diǎn)論文（hot paper）。該新聞稿等出后，美國(guó)科學(xué)促進(jìn)會(huì)（AAAS）旗下的EurekAlert!等十余家科學(xué)傳播平臺(tái)和網(wǎng)站進(jìn)行了轉(zhuǎn)載。
相關(guān)鏈接：
https://onlinelibrary.wiley.com/page/journal/15213773/homepage/press/201918press.html
https://www.eurekalert.org/pub_releases/2019-07/w-isf070319.php
內(nèi)容介紹：
“印跡”有識(shí)別受體分子HER2的專一位點(diǎn)的納米級(jí)顆粒為特別具有侵襲性、轉(zhuǎn)移形式的癌癥—HER2陽(yáng)性乳腺癌的治療升起了新的希望。據(jù)中國(guó)研究人員在Angewandte Chemie的報(bào)道，該納米粒子與HER2的選擇性結(jié)合顯著抑制了腫瘤細(xì)胞的增殖。
乳腺癌是女性最常見的癌癥形式，也是導(dǎo)致死亡的主要原因之一。約20%至30%的乳腺癌病例涉及治療效果極差的HER2陽(yáng)性。HER2指人表皮生長(zhǎng)因子受體2，一種能識(shí)別和結(jié)合特定生長(zhǎng)因子的蛋白質(zhì)。HER2跨越細(xì)胞膜：一部分突出到細(xì)胞內(nèi)部; 另一部分位于細(xì)胞表面。一旦與生長(zhǎng)因子對(duì)接，HER2的胞外區(qū)就與第二個(gè)密切相關(guān)的HER家族成員，HER1或HER3，結(jié)合形成異質(zhì)二聚體。這觸發(fā)了細(xì)胞內(nèi)的多步信號(hào)級(jí)聯(lián)，其嚴(yán)重涉及細(xì)胞分裂，轉(zhuǎn)移和供應(yīng)腫瘤的血管形成等過(guò)程。HER2陽(yáng)性腫瘤細(xì)胞含有顯著的更高濃度的HER2。一種當(dāng)前用于早期HER2陽(yáng)性腫瘤治療的方法利用抗體與HER2結(jié)合以阻斷其二聚化。由南京大學(xué)（中國(guó)）的劉震領(lǐng)導(dǎo)的研究人員現(xiàn)已開發(fā)出“分子印跡”生物相容性聚合物納米粒子，它能夠像抗體一樣識(shí)別HER2，以阻止其二聚化。
該納米粒子可以通過(guò)分子印跡制備，簡(jiǎn)言之，可聚合的混合物在稍后擬識(shí)別的（生物）分子的存在下聚合成納米球。該（生物）分子充當(dāng)一種印章，在納米球中留下納米級(jí)的“印痕”。然后，這些印痕與用于印跡的分子完美地匹配從而專一性地與其結(jié)合。與抗體相比，該納米球容易生產(chǎn)、價(jià)廉且化學(xué)穩(wěn)定。
對(duì)于印跡過(guò)程，研究人員使用特殊的方法（硼酸鹽親和可控定向表面印跡），這種方法特別可控，并且可以使用糖結(jié)構(gòu)單元（聚糖）作為模板進(jìn)行印跡。許多蛋白質(zhì)含有特定的“糖鏈”。這些糖鏈?zhǔn)仟?dú)特的，就像蛋白質(zhì)指紋一樣。研究人員使用這種來(lái)自HER2蛋白細(xì)胞外端的聚糖作為它們的“印章”。這使得它們能夠產(chǎn)生印跡納米顆粒，其特異性識(shí)別HER2并選擇性地結(jié)合HER2，并抑制二聚化。因此，它們能夠顯著減少體外腫瘤細(xì)胞的增殖和小鼠體內(nèi)腫瘤的生長(zhǎng)。相反，健康細(xì)胞基本上不受影響。
原文如下：
Imprinted Spheres Fight Breast Cancer
Inhibition of HER2 on tumor cells by molecularly imprinted nanoparticles
Nanoscopic particles “imprinted” with specific binding sites for the receptor molecule HER2 raise hope for a new way of treating a particularly aggressive, metastasizing form of cancer: HER2-positive breast cancer. As reported by Chinese researchers in the journal Angewandte Chemie, the selective binding of the nanoparticles to HER2 significantly inhibits multiplication of the tumor cells.
Breast cancer is the most common form of cancer in women and one of the leading causes of death. About 20 to 30 % of breast cancer cases involve the very poorly treatable HER2-positive variety. HER2 stands for Human Epidermal Growth Factor Receptor 2, a protein that recognizes and binds to a specific growth factor. HER2 spans across the cell membrane: one part protrudes into the interior of the cell; the other is on the cell surface. As soon as a growth factor docks, the extracellular parts of HER2 bind into a heterodimer with a second, closely related HER, such as HER1 or HER3. This triggers a multistep signal cascade within the cell, which is critically involved in processes like cell division, metastasis, and the formation of blood vessels that supply the tumor. HER2-positive tumor cells contain significantly higher concentrations of HER2. One current therapy for early-stage HER2-positive tumors is based on binding an antibody to HER2 to block the dimerization. Researchers led by Zhen Liu at Nanjing University (China) have now developed “molecularly imprinted” biocompatible polymer nanoparticles that recognize HER2 just as specifically as an antibody in order to prevent the dimerization.
Nanoparticles can be molecularly imprinted in that – to simplify – a polymerizable mixture is polymerized into nanospheres in the presence of the (bio)molecules they are supposed to recognize later. The (bio)molecules act as a kind of stamp, leaving nanoscopic “imprints” in the spheres. These then perfectly fit the molecules they were imprinted with and bind to them specifically. In contrast to antibodies, the nanospheres are easy and inexpensive to produce and are chemically stable.
For the imprinting process, the researchers use a special method (boronate affinity controllable oriented surface imprinting) that is particularly controllable and makes it possible to imprint using chains of sugar building blocks (glycans) as templates. Many proteins contain specific “sugar chains”. These are unique, like a protein fingerprint. The researchers used this kind of glycan from the extracellular end of the HER2 proteins as their “stamp”. This allowed them to produce imprinted nanoparticles that specifically recognize HER2 and selectively bind to it, inhibiting the dimerization. They were thus able to significantly reduce the multiplication of tumor cells in vitro and the growth of tumors in mice. In contrast, healthy cells were essentially unaffected.
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