2012年8月11日 訊 /生物谷BIOON/ --通過(guò)對(duì)人類(lèi)和小鼠前列腺癌細(xì)胞進(jìn)行研究,，來(lái)自約翰霍普金斯大學(xué)的癌癥成像專(zhuān)家開(kāi)發(fā)出了一種新型的方法來(lái)用于發(fā)現(xiàn)和消滅惡性的腫瘤細(xì)胞,。這種方法名為治療診斷學(xué)成像,，其可以直接打靶和追蹤潛在的藥物療法來(lái)專(zhuān)門(mén)消滅癌細(xì)胞。這種新方法依賴于結(jié)合在化療藥物的鈍化形式上,，來(lái)最終吸附于腫瘤細(xì)胞表面的特殊蛋白上,，最終檢測(cè)藥物對(duì)腫瘤的作用，這種高度的藥物-蛋白復(fù)合物（或者nanoplex）的結(jié)合允許其進(jìn)入癌細(xì)胞的內(nèi)部來(lái)發(fā)揮殺傷效應(yīng),。
相關(guān)研究成果刊登在了近日的國(guó)際雜志ACS Nano上,，這是首次揭示了化療法可以在分子水平被精確控制來(lái)最大化的殺死腫瘤細(xì)胞，同時(shí)盡可能減小副作用,。在治療診斷學(xué)成像實(shí)驗(yàn)中,，研究者僅僅研究了針對(duì)癌細(xì)胞的藥物，尤其是針對(duì)那些前列腺特異性膜抗原（PSMA）或者其細(xì)胞表面蛋白,。
研究者Bhujwalla表示,，我們的結(jié)果展示了非侵入性的成像方法以及針對(duì)表達(dá)PSMA的癌細(xì)胞的靶位療法。新技術(shù)可以針對(duì)任何形式的癌癥,，包括攜帶有HER-2/4的乳腺癌,、某些肝癌、肺癌以及可以表達(dá)特殊蛋白質(zhì)的腎臟癌等,。PSMA是在大部分的實(shí)體瘤血管中所表達(dá)的,，意味著新型療法應(yīng)當(dāng)進(jìn)行一般的成像和療法來(lái)針對(duì)癌癥。
在最近的一項(xiàng)實(shí)驗(yàn)中,，通過(guò)給小鼠注射前列腺癌腫瘤細(xì)胞,，研究者通過(guò)成像技術(shù)來(lái)追蹤抗癌藥物作用于腫瘤的過(guò)程。不同的新型藥物以放射性或者熒光分子為標(biāo)簽,，混合于癌癥細(xì)胞中,，有些有額外的PSMA。后續(xù)試驗(yàn)發(fā)現(xiàn)注射入三種不同濃度的藥物均不會(huì)給小鼠器官帶來(lái)?yè)p傷效應(yīng),。
研究者Pomper最后表示,，我們的治療診斷學(xué)成像方法揭示了最好的檢測(cè)和治療方法結(jié)合特異性的化學(xué)療法所表現(xiàn)出來(lái)的癌癥治療的最佳效果。運(yùn)用新方法,，我們可以攻擊多重的癌細(xì)胞,，提高藥物的效用。（生物谷Bioon.com）
編譯自：'Theranostic' Imaging Offers Means of Killing Prostate Cancer Cells
doi:10.1021/nn301725w
PMC:
PMID:
PSMA-Targeted Theranostic Nanoplex for Prostate Cancer Therapy
Zhihang Chen †, Marie-France Penet †, Sridhar Nimmagadda †‡, Cong Li †, Sangeeta R. Banerjee †, Paul T. Winnard , Jr.†, Dmitri Artemov †‡, Kristine Glunde †‡, Martin G. Pomper †‡, and Zaver M. Bhujwalla †‡*
Theranostic imaging, where diagnosis is combined with therapy, is particularly suitable for a disease that is as complex as cancer, especially now that genomic and proteomic profiling can provide an extensive “fingerprint” of each tumor. With such information, theranostic agents can be designed to personalize treatment and minimize damage to normal tissue. Here we have developed a nanoplex platform for theranostic imaging of prostate cancer (PCa). In these proof-of-principle studies, a therapeutic nanoplex containing multimodal imaging reporters was targeted to prostate-specific membrane antigen (PSMA), which is expressed on the cell surface of castrate-resistant PCa. The nanoplex was designed to deliver small interfering RNA (siRNA) along with a prodrug enzyme to PSMA-expressing tumors. Each component of the nanoplex was carefully selected to evaluate its diagnostic aspect of PSMA imaging and its therapeutic aspects of siRNA-mediated down-regulation of a target gene and the conversion of a prodrug to cytotoxic drug, using noninvasive multimodality imaging. Studies performed using two variants of human PC3-PCa cells and tumors, one with high PSMA expression level and another with negligible expression levels, demonstrated PSMA-specific uptake. In addition, down-regulation of the selected siRNA target, choline kinase (Chk), and the conversion of the nontoxic prodrug 5-fluorocytosine (5-FC) to cytotoxic 5-fluorouracil (5-FU) were also demonstrated with noninvasive imaging. The nanoplex was well-tolerated and did not induce liver or kidney toxicity or a significant immune response. The nanoplex platform described can be easily modified and applied to different cancers, receptors, and pathways to achieve theranostic imaging, as a single agent or in combination with other treatment modalities.
