Dual-Targeting Peptide-Guided Approach for Precision Delivery and Cancer Monitoring by Using a Safe Upconversion Nanoplatform

Shuai Zha, Ho Fai Chau, Wai Yin Chau, Lai Sheung Chan, Jun Lin, Kwok Wai Lo, William Chi-Shing Cho, Yim Ling Yip, Sai Wah Tsao, Paul J. Farrell, Liang Feng, Jin Ming Di (Corresponding Author), Ga Lai Law (Corresponding Author), Hong Lok Lung (Corresponding Author), Ka Leung Wong (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Article number2002919
JournalAdvanced Science
Volume8
Issue number5
DOIs
Publication statusPublished - 3 Mar 2021

Keywords

  • EBV-associated cancer imaging
  • lanthanide upconversion nanoplatform
  • peptide-guided precision cancer therapy
  • pH-responsive peptide
  • selective EBV-infected cytotoxicity

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)

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