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一种新型药物设计策略:源于金属富勒醇 Gd@C(OH)笼状包裹肿瘤的启示

A Novel Drug Design Strategy: An Inspiration from Encaging Tumor by Metallofullerenol Gd@C(OH).

机构信息

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, China.

College of Pharmacy, Shanxi Medical University, Taiyuan 030001, China.

出版信息

Molecules. 2019 Jun 27;24(13):2387. doi: 10.3390/molecules24132387.

Abstract

Cancer remains a major threat to human health worldwide. Cytotoxicity has imposed restrictions on the conventional cytotoxic drug-based chemotherapy. The rapidly-developing nanomedicine has shown great promise in revolutionizing chemotherapy with improved efficiency and reduced toxicity. Gd@C(OH), a novel endohedral metallofullerenol, was first reported by our research group to suppress tumor growth and metastasis efficiently without obvious toxicity. Gd@C(OH) imprisons tumors by facilitating the formation of surrounding fibrous layers which is different from chemotherapeutics that poison tumor cells. In this review, the authors first reported the antineoplastic activity of metallofullerenol Gd@C(OH) followed by further discussions on its new anti-cancer molecular mechanism-tumor encaging. On this basis, the unparalleled advantages of nanomedicine in the future drug design are discussed. The unique interaction modes of Gd@C(OH) with specific targeted biomolecules may shed light on a new avenue for drug design. Depending on the surface characteristics of target biomolecules, nanomedicine, just like a transformable and dynamic key, can self-assemble into suitable shapes to match several locks for the thermodynamic stability, suggesting the target-tailoring ability of nanomedicine.

摘要

癌症仍然是全球人类健康的主要威胁。细胞毒性对传统基于细胞毒性药物的化学疗法施加了限制。快速发展的纳米医学在提高效率和降低毒性方面显示出了巨大的潜力,有望彻底改变化学疗法。Gd@C(OH),一种新型的内包金属富勒醇,是由我们的研究小组首次报道的,它能够有效地抑制肿瘤生长和转移,而没有明显的毒性。Gd@C(OH) 通过促进周围纤维层的形成来困住肿瘤,这与毒害肿瘤细胞的化疗药物不同。在这篇综述中,作者首先报道了金属富勒醇 Gd@C(OH) 的抗肿瘤活性,随后进一步讨论了其新的抗癌分子机制——肿瘤包封。在此基础上,讨论了纳米医学在未来药物设计中的无与伦比的优势。Gd@C(OH) 与特定靶向生物分子的独特相互作用模式可能为药物设计开辟新途径。根据目标生物分子的表面特征,纳米医学就像一把可变形和动态的钥匙,可以自组装成合适的形状,以匹配几个锁的热力学稳定性,这表明了纳米医学的靶向能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a8b/6650816/33ebb559171b/molecules-24-02387-g001.jpg

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