PSMA-targeted theranostic nanoplex for prostate cancer therapy.
PSMA-targeted theranostic nanoplex for prostate cancer therapy.
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DOI：
10.1021/nn301725w
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发表时间：
2012-09-25
期刊：
影响因子：
17.1
通讯作者：
Bhujwalla, Zaver M.
中科院分区：
文献类型：
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作者：
Chen, Zhihang;Penet, Marie-France;Nimmagadda, Sridhar;Li, Cong;Banerjee, Sangeeta R.;Winnard, Paul T., Jr.;Artemov, Dmitri;Glunde, Kristine;Pomper, Martin G.;Bhujwalla, Zaver M.
治疗诊断成像将诊断与治疗相结合，特别适合像癌症这样复杂的疾病，尤其是现在基因组和蛋白质组分析可以提供每个肿瘤的广泛“指纹”。有了这些信息，就可以设计治疗诊断剂来进行个性化治疗并最大限度地减少对正常组织的损害。在这里，我们开发了一个用于前列腺癌（PCa）治疗诊断成像的纳米复合物平台。在这些原理验证研究中，含有多模态成像报告基因的治疗性纳米复合物靶向前列腺特异性膜抗原 (PSMA)，该抗原在去势抵抗性前列腺癌的细胞表面表达。纳米复合物旨在将小干扰 RNA (siRNA) 与前药酶一起递送至表达 PSMA 的肿瘤。纳米复合物的每个组分都经过精心选择，以使用非侵入性多模态成像来评估其 PSMA 成像的诊断方面以及 siRNA 介导的靶基因下调和前药转化为细胞毒性药物的治疗方面。使用人类 PC3-PCa 细胞和肿瘤的两种变体（一种具有高 PSMA 表达水平，另一种具有可忽略的表达水平）进行的研究证明了 PSMA 特异性摄取。此外，非侵入性成像还证明了所选 siRNA 靶标胆碱激酶 (Chk) 的下调，以及无毒前药 5-氟胞嘧啶 (5-FC) 向细胞毒性 5-氟尿嘧啶 (5-FU) 的转化。纳米复合物耐受性良好，不会引起肝或肾毒性或显着的免疫反应。所述的纳米复合物平台可以很容易地修改并应用于不同的癌症、受体和途径，以实现治疗诊断成像，作为单一药物或与其他治疗方式结合。
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.
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影响因子：
17.1
作者：
Li C;Penet MF;Wildes F;Takagi T;Chen Z;Winnard PT;Artemov D;Bhujwalla ZM
通讯作者：
Bhujwalla ZM
影响因子：
4.9
作者：
Kularatne, Sumith A.;Wang, Kevin;Low, Philip S.
通讯作者：
Low, Philip S.
影响因子：
2.8
作者：
Huang, XM;Bennett, M;Thorpe, PE
通讯作者：
Thorpe, PE
影响因子：
11.2
作者：
Krishnamachary B;Glunde K;Wildes F;Mori N;Takagi T;Raman V;Bhujwalla ZM
通讯作者：
Bhujwalla ZM
影响因子：
38.3
作者：
通讯作者：
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