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金纳米颗粒与C7H2和HuAL1肽的共功能化:增强的抗菌和抗肿瘤活性。

Co-Functionalization of Gold Nanoparticles with C7H2 and HuAL1 Peptides: Enhanced Antimicrobial and Antitumoral Activities.

作者信息

Formaggio Daniela M D, Magalhães Jéssica A, Andrade Vitor M, Conceição Katia, Anastácio Juliana M, Santiago Gabrielli S, Arruda Denise C, Tada Dayane B

机构信息

Laboratory of Nanomaterials and Nanotoxicology, Institute of Science and Technology, Federal University of São Paulo (UNIFESP), São José dos Campos 12231-280, SP, Brazil.

Laboratory of Peptide Biochemistry, Institute of Science and Technology, Federal University of São Paulo (UNIFESP), São José dos Campos 12231-280, SP, Brazil.

出版信息

Pharmaceutics. 2022 Jun 23;14(7):1324. doi: 10.3390/pharmaceutics14071324.

Abstract

The functionalization of nanoparticles with therapeutic peptides has been pointed out as a promising strategy to improve the applications of these molecules in the field of health sciences. Peptides are highly bioactive but face several limitations such as low bioavailability due to the difficulty of overcoming the physiological barriers in the body and their degradation by enzymes. In this work, gold nanoparticles (AuNPs) were co-functionalized with two therapeutic peptides simultaneously. The peptides from the complementary determining region of monoclonal antibodies, composed of the amino acid sequences YISCYNGATSYNQKFK (C7H2) and RASQSVSSYLA (HuAL1) were chosen for having exhibited antitumor and antimicrobial activity before. The peptides-conjugated AuNPs were characterized regarding size, morphology, and metal concentration by using TEM, dynamic light scattering, and ICP-OES techniques. Then, peptides-conjugated AuNPs were evaluated regarding the antimicrobial activity against , , and . The antitumoral activity was evaluated in vitro by cell viability assays with metastatic melanoma cell line (B16F10-Nex2) and the cytotoxicity was evaluated against human foreskin fibroblast (Hs68) cell line. Finally, in vivo assays were performed by using a syngeneic animal model of metastatic melanoma. Our findings have highlighted the potential application of the dual-peptide AuNPs in order to enhance the antitumor and antimicrobial activity of peptides.

摘要

用治疗性肽对纳米颗粒进行功能化修饰已被指出是一种有前景的策略,可改善这些分子在健康科学领域的应用。肽具有高度生物活性,但面临一些限制,例如由于难以克服体内生理屏障以及被酶降解而导致生物利用度低。在这项工作中,金纳米颗粒(AuNPs)同时与两种治疗性肽进行了共功能化修饰。选择了来自单克隆抗体互补决定区的肽,其氨基酸序列分别为YISCYNGATSYNQKFK(C7H2)和RASQSVSSYLA(HuAL1),因为它们之前已表现出抗肿瘤和抗菌活性。通过透射电子显微镜(TEM)、动态光散射和电感耦合等离子体发射光谱(ICP - OES)技术对肽偶联的AuNPs的尺寸、形态和金属浓度进行了表征。然后,评估了肽偶联的AuNPs对[具体菌种1]、[具体菌种2]和[具体菌种3]的抗菌活性。通过对转移性黑色素瘤细胞系(B16F10 - Nex2)进行细胞活力测定,体外评估了其抗肿瘤活性,并针对人包皮成纤维细胞(Hs68)细胞系评估了细胞毒性。最后,使用转移性黑色素瘤的同基因动物模型进行了体内试验。我们的研究结果突出了双肽AuNPs在增强肽的抗肿瘤和抗菌活性方面的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22c5/9317637/6194c3c443c2/pharmaceutics-14-01324-g001.jpg

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