Dual-targeting peptide-guided approach for precision delivery and cancer monitoring by using a safe upconversion nanoplatform
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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‐Pn, n = 5, 6, and 7). A synergistic combination of the transmembrane LMP1 targeting ability and the pH responsiveness of UCNP‐Pn 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.
Date Issued
2021-01-06
Date Acceptance
2021-01-01
Citation
Advanced Science, 2021, 8 (5), pp.1-15
ISSN
2198-3844
Publisher
Wiley Open Access
Start Page
1
End Page
15
Journal / Book Title
Advanced Science
Volume
8
Issue
5
Copyright Statement
© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Medical Research Council
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000605170500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
MR/S022597/1
Subjects
Science & Technology
Physical Sciences
Technology
Chemistry, Multidisciplinary
Nanoscience & Nanotechnology
Materials Science, Multidisciplinary
Chemistry
Science & Technology - Other Topics
Materials Science
EBV‐
associated cancer imaging
lanthanide upconversion nanoplatform
peptide‐
guided precision cancer therapy
pH‐
responsive peptide
selective EBV‐
infected cytotoxicity
EPSTEIN-BARR-VIRUS
LANTHANIDE NANOPARTICLES
PROTEIN
LMP1
LUMINESCENCE
EBNA1
NANOMATERIALS
INHIBITION
NANOPROBES
Publication Status
Published
Article Number
ARTN 2002919
Date Publish Online
2021-01-06