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肿瘤归巢肽及其在晚期癌症治疗中的应用。

Tumor-homing peptide and its utility for advanced cancer medicine.

机构信息

Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

出版信息

Cancer Sci. 2021 Jun;112(6):2118-2125. doi: 10.1111/cas.14909. Epub 2021 May 7.

Abstract

Cell-penetrating peptides, such as antibodies, have gained great attention as tools for the development of specific delivery systems for payloads, which might be applied as non-invasive carriers in vivo. Among these, tumor-homing peptides recently have been studied for use in tumor medicine. Tumor-homing peptides are oligopeptides, usually consisting of 30 or fewer amino acids that are efficiently and specifically incorporated into tumor cells, suggesting their potential use in establishing novel non-invasive tumor imaging systems for diagnostic and therapeutic applications. Here, we briefly introduce the biological characteristics of our tumor-homing peptides, focusing especially on those developed using a random peptide library constructed using mRNA display technology. The advantage of the tumor-homing peptides is their biological safety, given that these molecules do not show significant cytotoxicity against non-neoplastic cells; lack serious antigenicity, which alternatively might evoke unfavorable immune responses and inflammation in vivo; and are rapidly incorporated into target cells/tissues, with rates exceeding those seen for antibodies. Given their small size, tumor-homing peptides also are easy to modify and redesign. Based on these merits, tumor-homing peptides are expected to find wide application in various aspects of tumor medicine, including imaging diagnostics (eg, with dye-conjugated probes for direct visualization of invasive/metastatic tumor lesions in vivo) and therapeutics (eg, using peptide-drug conjugates [PDCs] for tumor targeting). Although further evidence will be required to demonstrate their practical utility, tumor-homing peptides are expected to show great potential as a next-generation bio-tool contributing to precision medicine for cancer patients.

摘要

细胞穿透肽,如抗体,作为载药的特异性递药系统的工具得到了广泛关注,其可作为非侵入性载体在体内应用。其中,肿瘤归巢肽最近已被研究用于肿瘤医学。肿瘤归巢肽是由 30 个或更少的氨基酸组成的寡肽,能够有效地、特异性地被肿瘤细胞摄取,这表明它们可能用于建立新的非侵入性肿瘤成像系统,用于诊断和治疗应用。在这里,我们简要介绍了我们的肿瘤归巢肽的生物学特性,特别是使用基于 mRNA 展示技术构建的随机肽文库开发的肿瘤归巢肽。这些肿瘤归巢肽的优点在于其生物学安全性,因为这些分子对非肿瘤细胞没有明显的细胞毒性;缺乏严重的抗原性,否则可能会在体内引起不利的免疫反应和炎症;并且可以快速进入靶细胞/组织,其进入速度超过抗体。由于其体积小,肿瘤归巢肽也易于修饰和重新设计。基于这些优点,肿瘤归巢肽有望在肿瘤医学的各个方面得到广泛应用,包括成像诊断(例如,用染料偶联探针直接可视化体内侵袭性/转移性肿瘤病变)和治疗(例如,使用肽-药物偶联物 [PDC] 进行肿瘤靶向)。尽管还需要进一步的证据来证明其实际用途,但肿瘤归巢肽有望作为下一代生物工具,为癌症患者的精准医学做出巨大贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ac/8177760/34d3df8113cf/CAS-112-2118-g006.jpg

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