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*, Ga Lai Law*, Hong Lok Lung*, Ka-Leung Wong*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

55 Citations (Scopus)


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
Number of pages15
JournalAdvanced Science
Issue number5
Early online date6 Jan 2021
Publication statusPublished - 3 Mar 2021

Scopus Subject Areas

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

User-Defined Keywords

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


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