A nanometer-sized protease inhibitor for precise cancer diagnosis and treatment
A nanometer-sized protease inhibitor for precise cancer diagnosis and treatment
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用于癌症精准诊断和治疗的纳米级蛋白酶抑制剂
DOI：
10.1039/c9tb02081k
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发表时间：
2020-01-21
影响因子：
7
通讯作者：
Chen, Zhuo
中科院分区：
文献类型：
--
作者：
Hu, Ping;Shang, Le;Chen, Zhuo
抑制癌前蛋白酶是一种有效的抗癌策略。然而，蛋白酶抑制剂大多以小分子或肽的形式发展，通常缺乏代谢稳定性。快速清除明显削弱了这些抑制剂的抗肿瘤作用。在这项研究中，我们报道了一种纳米大小的促癌蛋白酶抑制剂，抑瘤性14 (st14)，已被报道为多种癌症的有效预后标志物。该st14抑制剂由重组st14抑制剂（KD1）与碳量子点（CQDs）偶联而成。CQD-KD1不仅在生化实验中表现出高效抑制st14活性，而且显著抑制乳腺癌细胞的侵袭。与原重组KD1相比，CQD-KD1在血浆和肿瘤部位的滞留时间延长，因为肾脏清除率降低。一致地，CQD-KD1在体内表现出抑制肿瘤生长和肿瘤转移的增强效果。此外，CQD-KD1通过特异性靶向肿瘤细胞表面过表达的st14，对癌移植小鼠的肿瘤组织进行精确成像，这表明CQD-KD1是荧光引导肿瘤切除手术的有效探针。综上所述，本研究表明CQD-KD1是一种非常有效的癌症诊断和治疗药物。
Inhibition of pro-cancer proteases is a potent anticancer strategy. However, protease inhibitors are mostly developed in the forms of small molecules or peptides, which normally suffer from insufficient metabolic stability. The fast clearance significantly impairs the antitumor effects of these inhibitors. In this study, we report a nanometer-sized inhibitor of a pro-cancer protease, suppressor of tumorigenicity 14 (st14), which has been reported as a potent prognostic marker for multiple cancers. This st14 inhibitor was fabricated by conjugating a recombinant st14 inhibitor (KD1) with carbon quantum dots (CQDs). CQD-KD1 not only demonstrated high potency of inhibiting st14 activity in biochemical experiments, but also remarkably suppressed the invasion of breast cancer cells. In contrast to the original recombinant KD1, CQD-KD1 demonstrated a prolonged retention time in plasma and at the tumor site because of the reduced renal clearance. Consistently, CQD-KD1 demonstrated enhanced efficacies of suppressing tumor growth and cancer metastases in vivo. In addition, CQD-KD1 precisely imaged tumor tissues in cancer-grafted mice by specifically targeting the over-expressed st14 on the tumor cell surface, which indicates CQD-KD1 as a potent probe for the fluorescence guided surgery of tumor resection. In conclusion, this study demonstrates that CQD-KD1 is a highly potent diagnostic and therapeutic agent for cancer treatments.