Tumor-targeting cell-penetrating peptide, p28, for glioblastoma imaging and therapy.
Tumor-targeting cell-penetrating peptide, p28, for glioblastoma imaging and therapy.
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DOI：
10.3389/fonc.2022.940001
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发表时间：
2022
影响因子：
4.7
通讯作者：
Yamada, Tohru
中科院分区：
文献类型：
--
作者：
Mander, Sunam;Naffouje, Samer A.;Gao, Jin;Li, Weiguo;Christov, Konstantin;Green, Albert;Bongarzone, Ernesto R.;Das Gupta, Tapas K.;Yamada, Tohru
尽管癌症研究最近取得了进展，但多形性胶质母细胞瘤（GBM）仍然是一种高度侵袭性的脑肿瘤，因为其治疗选择有限。目前的标准治疗包括手术、随后的放疗和辅助化疗。然而，没有图像引导的手术通常很难实现最大程度的安全切除，因为很难精确辨别要从周围脑组织中切除的病灶。此外，辅助化疗的疗效还受到治疗药物通过血脑屏障（BBB）进入脑组织的渗透性差以及缺乏肿瘤靶向性的限制。在这方面，我们利用肿瘤靶向细胞穿透肽p28作为治疗剂来提高现有GBM化疗剂的疗效，并作为荧光成像剂的载体来明确识别GBM。在这里，我们证明近红外 (NIR) 成像剂 ICG-p28（FDA 批准的 NIR 染料、吲哚菁绿 ICG 和肿瘤靶向 p28 肽的化学缀合物）可以优先定位多种 GBM 动物模型中的肿瘤。此外，异种移植研究表明，p28作为治疗剂可以增强替莫唑胺（TMZ）的细胞毒活性，替莫唑胺是少数有效治疗脑肿瘤的药物之一。总的来说，我们的研究结果强调了肿瘤靶向肽的重要作用，它在术中图像引导手术和开发 GBM 新治疗策略方面具有巨大潜力。
Despite recent advances in cancer research, glioblastoma multiforme (GBM) remains a highly aggressive brain tumor as its treatment options are limited. The current standard treatment includes surgery followed by radiotherapy and adjuvant chemotherapy. However, surgery without image guidance is often challenging to achieve maximal safe resection as it is difficult to precisely discern the lesion to be removed from surrounding brain tissue. In addition, the efficacy of adjuvant chemotherapy is limited by poor penetration of therapeutics through the blood-brain barrier (BBB) into brain tissues, and the lack of tumor targeting. In this regard, we utilized a tumor-targeting cell-penetration peptide, p28, as a therapeutic agent to improve the efficacy of a current chemotherapeutic agent for GBM, and as a carrier for a fluorescence imaging agent for a clear identification of GBM. Here, we show that a near-infrared (NIR) imaging agent, ICG-p28 (a chemical conjugate of an FDA-approved NIR dye, indocyanine green ICG, and tumor-targeting p28 peptide) can preferentially localize tumors in multiple GBM animal models. Moreover, xenograft studies show that p28, as a therapeutic agent, can enhance the cytotoxic activity of temozolomide (TMZ), one of the few effective drugs for brain tumors. Collectively, our findings highlight the important role of the tumor-targeting peptide, which has great potential for intraoperative image-guided surgery and the development of new therapeutic strategies for GBM.
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影响因子：
45.3
作者：
Hegi, Monika E.;Liu, Lili;Gilbert, Mark R.
通讯作者：
Gilbert, Mark R.
影响因子：
28.5
作者：
Festuccia C;Mancini A;Colapietro A;Gravina GL;Vitale F;Marampon F;Delle Monache S;Pompili S;Cristiano L;Vetuschi A;Tombolini V;Chen Y;Mehrling T
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Mehrling T
影响因子：
17.1
作者：
Huang K;Ma H;Liu J;Huo S;Kumar A;Wei T;Zhang X;Jin S;Gan Y;Wang PC;He S;Zhang X;Liang XJ
通讯作者：
Liang XJ
影响因子：
9.8
作者：
Mehta, Rajeshwari R.;Yamada, Tohru;Das Gupta, Tapas K.
通讯作者：
Das Gupta, Tapas K.
影响因子：
51.1
作者：
Berger, F;Gay, E;Wion, D
通讯作者：
Wion, D