Ko Joshua K, Auyeung Kathy K
Centre for Cancer and Inflammation Research, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Hong Kong SAR, China.
Curr Med Chem. 2014;21(21):2346-56. doi: 10.2174/0929867321666140205132124.
Cancer cells can express specific membrane proteins, which act as biomarkers for chemotherapeutic targeting. Functional peptides possess unique properties that will ensure efficacy, selectivity, specificity and low toxicity when used as therapeutic agents. Therapeutic peptides have been derived in treatment of cancers through improvement of cellular uptake, drug targeting and vaccine development. Peptides from natural source have been used for chemoprevention and therapy of various cancers. These include peptides derived from food, marine products, venom components and other animal constituents. Besides, chemically- and recombinantly-synthesized peptides have also been produced and extensively studied in contemporary applications. Improvement of tumor targeting is essential for chemotherapeutic development. This can be achieved through enhancement of intracellular delivery and/or increased specific binding affinity to cancer cells by pore-forming and cytotoxic peptides. Cytotoxic peptides such as the Bcl-2 family members can induce receptor-specific binding to tumor cells and promote apoptosis by targeting lipid membranes. This approach has some limitations in targeting, penetration and localization within tumors. Cell-penetrating peptides (CPPs) belong to a new class of tumor-targeting peptides that can facilitate internalization of tumor markers and/or chemotherapeutic drugs. In order to overcome the problem of serum instability in classical CPPs (e.g. Tat), newer classes of CPPs has been recently introduced. Nevertheless, some cyclized CPPs can further enhance cellular uptake and binding selectivity when compared to activities of their linear counterpart, especially when treating chemoresistant tumors. This review compiles the use of effective tumor-targeting peptides including novel CPPs that represents new therapeutic strategies for the treatment of cancers.
癌细胞能够表达特定的膜蛋白，这些膜蛋白可作为化疗靶向的生物标志物。功能性肽具有独特的性质，用作治疗剂时能确保疗效、选择性、特异性和低毒性。治疗性肽已通过改善细胞摄取、药物靶向和疫苗开发用于癌症治疗。天然来源的肽已用于多种癌症的化学预防和治疗。这些包括源自食物、海产品、毒液成分和其他动物成分的肽。此外，化学合成和重组合成的肽也已生产出来，并在当代应用中得到广泛研究。改善肿瘤靶向对于化疗发展至关重要。这可通过增强细胞内递送和/或通过成孔肽和细胞毒性肽增加与癌细胞的特异性结合亲和力来实现。细胞毒性肽如Bcl-2家族成员可诱导与肿瘤细胞的受体特异性结合，并通过靶向脂质膜促进细胞凋亡。这种方法在肿瘤靶向、渗透和定位方面存在一些局限性。细胞穿透肽（CPPs）属于一类新型的肿瘤靶向肽，可促进肿瘤标志物和/或化疗药物的内化。为了克服经典CPPs（如Tat）中血清稳定性的问题，最近引入了更新类型的CPPs。然而，与线性对应物的活性相比，一些环化CPPs可进一步增强细胞摄取和结合选择性，尤其是在治疗化疗耐药肿瘤时。本综述汇编了有效肿瘤靶向肽的应用，包括代表癌症治疗新策略的新型CPPs。
