Dual‐Targeting Peptide‐Guided Approach for Precision Delivery and Cancer Monitoring by Using a Safe Upconversion Nanoplatform,Advanced Science

当前位置： X-MOL 学术 › Adv. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Dual‐Targeting Peptide‐Guided Approach for Precision Delivery and Cancer Monitoring by Using a Safe Upconversion Nanoplatform
Advanced Science ( IF 14.3 ) Pub Date : 2021-01-06 , DOI: 10.1002/advs.202002919
Shuai Zha ₁ , Ho-Fai Chau ₁ , Wai Yin Chau ₂ , Lai Sheung Chan ₁ , Jun Lin ₃ , Kwok Wai Lo ₄ , William Chi-Shing Cho ₅ , Yim Ling Yip ₆ , Sai Wah Tsao ₆ , Paul J Farrell ₇ , Liang Feng ₈ , Jin Ming Di ₉ , Ga-Lai Law ₈ , Hong Lok Lung ₁ , Ka-Leung Wong ₁

Affiliation

Department of Chemistry, Hong Kong Baptist University, 224 Waterloo Road, Kowloon, Hong Kong SAR, 000000, P. R. China.
Department of Biology, Hong Kong Baptist University, 224 Waterloo Road, Kowloon, Hong Kong SAR, 000000, P. R. China.
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130000, P. R. China.
Department of Anatomical & Cellular Pathology and State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Kowloon, Hong Kong SAR, 000000, P. R. China.
Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong SAR, 000000, P. R. China.
School of Biomedical Sciences, The University of Hong Kong, Kowloon, Hong Kong SAR, 000000, P. R. China.
Section of Virology, Imperial College Faculty of Medicine, Norfolk Place, London, W12 0BZ, UK.
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, 000000, P. R. China.
Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, 510630, P. R. China.

Using Epstein‐Barr virus (EBV)‐induced cancer cells and HeLa cells as a comparative study model, a novel and safe dual‐EBV‐oncoproteins‐targeting pH‐responsive peptide engineering, coating, and guiding approach to achieve precision targeting and treatment strategy against EBV‐associated cancers is introduced. Individual functional peptide sequences that specifically bind to two overexpressed EBV‐specific oncoproteins, EBNA1 (a latent cellular protein) and LMP1 (a transmembrane protein), are engineered in three different ways and incorporated with a pH‐sensitive tumor microenvironment (TME)‐cleavable linker onto the upconversion nanoparticles (UCNP) NaGdF₄:Yb³⁺, Er³⁺@NaGdF₄ (UCNP‐P_n, n = 5, 6, and 7). A synergistic combination of the transmembrane LMP1 targeting ability and the pH responsiveness of UCNP‐P_n is found to give specific cancer differentiation with higher cellular uptake and accumulation in EBV‐infected cells, thus a lower dose is needed and the side effects and health risks from treatment would be greatly reduced. It also gives responsive UC signal enhancement upon targeted dual‐protein binding and shows efficacious EBV cancer inhibition in vitro and in vivo. This is the first example of simultaneous imaging and inhibition of two EBV latent proteins, and serves as a blueprint for next‐generation peptide‐guided precision delivery nanosystem for the safe monitoring and treatment against one specific cancer.

中文翻译：

使用安全上转换纳米平台进行精准递送和癌症监测的双靶向肽引导方法

以 Epstein-Barr 病毒（EBV）诱导的癌细胞和 HeLa 细胞作为比较研究模型，一种新颖且安全的双 EBV 癌蛋白靶向 pH 响应肽工程、涂层和引导方法，以实现精准靶向和治疗策略介绍了针对 EBV 相关癌症的药物。特异性结合两种过表达的 EBV 特异性癌蛋白 EBNA1（一种潜伏细胞蛋白）和 LMP1（一种跨膜蛋白）的单个功能肽序列以三种不同的方式进行设计，并与 pH 敏感的肿瘤微环境 (TME) 可裂解相结合连接到上转换纳米颗粒 (UCNP) NaGdF ₄ :Yb ³⁺ , Er ³⁺ @NaGdF ₄ (UCNP-P _n , n = 5、6 和 7)。跨膜 LMP1 靶向能力和 UCNP-P _n的 pH 响应能力的协同组合可实现特定的癌症分化，并在 EBV 感染的细胞中具有更高的细胞摄取和积累，因此需要较低的剂量，并且副作用和健康风险较低治疗效果将大大降低。它还在靶向双蛋白结合时提供响应性 UC 信号增强，并在体外和体内显示出有效的 EBV 癌症抑制作用。这是同时成像和抑制两种 EBV 潜蛋白的第一个例子，并作为下一代肽引导精准递送纳米系统的蓝图，用于安全监测和治疗一种特定癌症。

更新日期：2021-03-03

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11