Cell-Penetrating Peptides: Applications in Tumor Diagnosis and Therapeutics.
Cell-Penetrating Peptides: Applications in Tumor Diagnosis and Therapeutics.
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DOI：
10.3390/pharmaceutics13060890
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发表时间：
2021-06-15
期刊：
影响因子：
5.4
通讯作者：
Zahid M
中科院分区：
文献类型：
--
作者：
Stiltner J;McCandless K;Zahid M
自从它们在25年前被发现以来，细胞穿透肽（CPP）的过剩及其应用已经飞速发展。这些5到30个氨基酸长度的肽具有打破细胞膜屏障的独特特性，同时以完整的功能形式携带比它们自己大的货物进入细胞。CPPs可以与荧光团、可激活探针、放射性同位素或造影剂结合，用于成像组织（如肿瘤）。CPPs转运到细胞中没有单一的机制，因此，许多CPPs被多种细胞类型所吸收，这给肿瘤特异性转运带来了挑战，并阻碍了临床疗效。为了解决这一问题，已经开发了不同的策略，并通过构建特定的细胞活化形式来衍生CPPs以更好地靶向，从而提高其诊断潜力。这些方法目前被用来成像表达整合素的肿瘤，乳腺癌细胞，人组织细胞淋巴瘤和蛋白酶分泌纤维肉瘤细胞，仅举几例。此外，寻找安全有效的恶性肿瘤治疗方法一直是一个活跃的研究领域。CPPs可以通过靶向将药物输送到肿瘤中来避免传统治疗方法治疗癌症时发现的许多并发症，从而减少脱靶副作用，这是目前使用的传统化疗方法无法实现的壮举。无数类型的化疗药物，如酪氨酸激酶抑制剂、抗肿瘤抗体和纳米颗粒，可以在功能上附着在这些肽上，从而有可能将现有的和新型的癌症治疗药物直接输送到肿瘤组织。虽然需要进行大量的研究来克服这些肽的潜在问题，但它们比目前治疗癌症的机制提供了重大的进步。在这篇综述中，我们对研究进行了简要概述，并对这些新肽在癌症诊断和治疗中的作用进行了全面的回顾，从而确定了CPPs。
Since their identification over twenty-five years ago, the plethora of cell-penetrating peptides (CPP) and their applications has skyrocketed. These 5 to 30 amino acid in length peptides have the unique property of breaching the cell membrane barrier while carrying cargoes larger than themselves into cells in an intact, functional form. CPPs can be conjugated to fluorophores, activatable probes, radioisotopes or contrast agents for imaging tissues, such as tumors. There is no singular mechanism for translocation of CPPs into a cell, and therefore, many CPPs are taken up by a multitude of cell types, creating the challenge of tumor-specific translocation and hindering clinical effectiveness. Varying strategies have been developed to combat this issue and enhance their diagnostic potential by derivatizing CPPs for better targeting by constructing specific cell-activated forms. These methods are currently being used to image integrin-expressing tumors, breast cancer cells, human histiocytic lymphoma and protease-secreting fibrosarcoma cells, to name a few. Additionally, identifying safe, effective therapeutics for malignant tumors has long been an active area of research. CPPs can circumvent many of the complications found in treating cancer with conventional therapeutics by targeted delivery of drugs into tumors, thereby decreasing off-target side effects, a feat not achievable by currently employed conventional chemotherapeutics. Myriad types of chemotherapeutics such as tyrosine kinase inhibitors, antitumor antibodies and nanoparticles can be functionally attached to these peptides, leading to the possibility of delivering established and novel cancer therapeutics directly to tumor tissue. While much research is needed to overcome potential issues with these peptides, they offer a significant advancement over current mechanisms to treat cancer. In this review, we present a brief overview of the research, leading to identification of CPPs with a comprehensive state-of-the-art review on the role of these novel peptides in both cancer diagnostics as well as therapeutics.
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影响因子：
8.8
作者：
Akashi, Y.;Oda, T.;Ohara, Y.;Miyamoto, R.;Kurokawa, T.;Hashimoto, S.;Enomoto, T.;Yamada, K.;Satake, M.;Ohkohchi, N.
通讯作者：
Ohkohchi, N.
影响因子：
3.7
作者：
Alves ID;Bechara C;Walrant A;Zaltsman Y;Jiao CY;Sagan S
通讯作者：
Sagan S
影响因子：
3.4
作者：
Hällbrink, M;Florén, A;Langel, Ü
通讯作者：
Langel, Ü
影响因子：
64.5
作者：
GREEN, M;ISHINO, M;LOEWENSTEIN, PM
通讯作者：
LOEWENSTEIN, PM
DOI：
10.1073/pnas.1114518108
发表时间：
2011-10-18
影响因子：
11.1
作者：
Agemy, Lilach;Friedmann-Morvinski, Dinorah;Ruoslahti, Erkki
通讯作者：
Ruoslahti, Erkki