Responsive upconversion nanoprobe for monitoring and inhibition of EBV-associated cancersviatargeting EBNA1

Abstract

Non-responsive emission enhancement is the disadvantage of upconversion nanomaterials (UCNM) when compared with conventional organic based agents for molecular imaging. We herein show a new strategy by conjugating NaGdF4:Yb3+,Er3+@NaGdF4 (UCNP) with peptides to achieve responsive UC emission enhancement upon binding to a targeted protein - EBNA1. EBNA1 is a well-known viral latent protein for the EBV-associated cancer. Peptide-coating of the functionalized core-shell nanoparticle diminishes upconverted emission intensity drastically. However, the peptide-coated UCNP shows selective and responsive UC emission enhancement via aggregation with the targeted protein. This phenomenon paves a new way for UCNM in molecular imaging.

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

“…A size increase of around 3 nm in UCNP-P n (n = 5, 6, and 7) compared to UCNP was observed, implying successful bioconjugation of UCNP with P n (n = 5, 6, and 7). Likewise, the old nanoprobe UCNP-P 4 , [33] which targets EBNA1, was also synthesized with uniform morphology, as shown in Figure S4 (Supporting Information). UCNP-P 4 was included as a control compound.…”

Reactivation of Epstein–Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn 2+ -chelating function

“…Specific inhibition of EBNA1 by dominant-negative EBNA1 mutants (6), antisense oligonucleotides (7), oriP blocking agents, and small molecules/macromolecules (8–12) is shown to inhibit tumor cell growth. Furthermore, our recent study shows that the EBNA1-binding peptide P 4 derived from the EBNA1 dimeric interface is able to interfere with the homodimerization of the EBNA1 monomer and suppress EBV-infected cell growth (13–16).…”

The Therapeutic Potential of Targeting BARF1 in EBV-Associated Malignancies

“…Given that the N-terminal region of BARF1 is responsible for binding hCSF1 and BARF1-mediated cell growth enhancement and malignant transformation, future studies are required to determine whether agents which target the BARF1 N-terminus specifically are able to block the oncogenic and immunomodulatory functions of the BARF1 protein [ 23 , 24 , 35 ]. Our group has developed EBNA1-specific fluorescent peptide probes (L2P4 and UCNP-P4) which target the EBNA1 dimerization site [ 67 , 68 ]. These probes have proved successful not only in the imaging of tumour xenografts in vivo but also in suppressing the growth of EBV-positive tumour cells in vitro and in vivo.…”

“…Therefore, BARF1 may constitute a viable candidate for peptide-based therapy. Recently, our group has engineered two EBNA1-specific probes, L2P4 and UCNP-P4 [ 67 , 68 ]. The L2P4 probe contains a water-soluble fluorophore L2 and an EBNA1-binding peptide, P4 (YFMVF-GG-RrRK), incorporated with a nuclear localization sequence (RrRK) moiety, which allows nucleus penetration and localization.…”