Lanthanide-Based Peptide-Directed Visible/Near-Infrared Imaging and Inhibition of LMP1

Ho-Fai Chau; Yue Wu; Wan-Yiu Fok; Waygen Thor; William Chi-Shing Cho; Ping'an Ma; Jun Lin; Nai-Ki Mak; Jean-Claude G. Bunzli; Lijun Jiang; Nicholas J. Long; Hong Lok Lung; Ka-Leung Wong

doi:10.1021/jacsau.1c00187

Lanthanide-Based Peptide-Directed Visible/Near-Infrared Imaging and Inhibition of LMP1

Ho-Fai Chau, Yue Wu, Wan-Yiu Fok, Waygen Thor, William Chi-Shing Cho, Ping'an Ma, Jun Lin, Nai-Ki Mak, Jean-Claude G. Bunzli^*, Lijun Jiang^*, Nicholas J. Long^*, Hong Lok Lung^*, Ka-Leung Wong^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › peer-review

13 Citations (Scopus)

Abstract

A lanthanide-based peptide-directed bioprobe LnP19 (Ln = Eu or Yb) is designed as an impressive example of a small molecule-based dual-functional probe for the EBV oncoprotein LMP1. The peptide P19 (Pra-KAhx-K-LDLALK-FWLY-K-IVMSDKW-K-RrRK) is designed to selectively bind to LMP1 by mimicking its TM1 region during oligomerization in lipid rafts while signal transduction is significantly suppressed. Immunofluorescence imaging and Western blotting results reveal that P19 can effectively inactivate the oncogenic cellular pathway nuclear factor κB (NF-κB) and contribute to a selective cytotoxic effect on LMP1-positive cells. By conjugation with cyclen-based europium(III) and ytterbium(III) complexes, EuP19 and YbP19 were constructed to offer visible and near-infrared LMP1-targeted imaging and cancer monitoring. In addition to the ability to target and inhibit LMP1 and to selective inhibit LMP1-positive cells, selective growth inhibition toward the LMP1-positive tumor by LnP19 is also demonstrated.

Original language	English
Pages (from-to)	1034-1043
Number of pages	10
Journal	Journal of American Chemical Society AU
Volume	1
Issue number	7
Early online date	20 Jun 2021
DOIs	https://doi.org/10.1021/jacsau.1c00187
Publication status	Published - 26 Jul 2021

User-Defined Keywords

LMP1-targeted imaging EBV
EBV-related cancer
lanthanide(III) luminescence
theranostic agent

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/jacsau.1c00187

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@article{8036b7da237f4263b7766aeeebf086d2,

title = "Lanthanide-Based Peptide-Directed Visible/Near-Infrared Imaging and Inhibition of LMP1",

abstract = "A lanthanide-based peptide-directed bioprobe LnP19 (Ln = Eu or Yb) is designed as an impressive example of a small molecule-based dual-functional probe for the EBV oncoprotein LMP1. The peptide P19 (Pra-KAhx-K-LDLALK-FWLY-K-IVMSDKW-K-RrRK) is designed to selectively bind to LMP1 by mimicking its TM1 region during oligomerization in lipid rafts while signal transduction is significantly suppressed. Immunofluorescence imaging and Western blotting results reveal that P19 can effectively inactivate the oncogenic cellular pathway nuclear factor κB (NF-κB) and contribute to a selective cytotoxic effect on LMP1-positive cells. By conjugation with cyclen-based europium(III) and ytterbium(III) complexes, EuP19 and YbP19 were constructed to offer visible and near-infrared LMP1-targeted imaging and cancer monitoring. In addition to the ability to target and inhibit LMP1 and to selective inhibit LMP1-positive cells, selective growth inhibition toward the LMP1-positive tumor by LnP19 is also demonstrated.",

keywords = "LMP1-targeted imaging EBV, EBV-related cancer, lanthanide(III) luminescence, theranostic agent",

author = "Ho-Fai Chau and Yue Wu and Wan-Yiu Fok and Waygen Thor and Cho, {William Chi-Shing} and Ping'an Ma and Jun Lin and Nai-Ki Mak and Bunzli, {Jean-Claude G.} and Lijun Jiang and Long, {Nicholas J.} and Lung, {Hong Lok} and Ka-Leung Wong",

year = "2021",

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language = "English",

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TY - JOUR

T1 - Lanthanide-Based Peptide-Directed Visible/Near-Infrared Imaging and Inhibition of LMP1

AU - Chau, Ho-Fai

AU - Wu, Yue

AU - Fok, Wan-Yiu

AU - Thor, Waygen

AU - Cho, William Chi-Shing

AU - Ma, Ping'an

AU - Lin, Jun

AU - Mak, Nai-Ki

AU - Bunzli, Jean-Claude G.

AU - Jiang, Lijun

AU - Long, Nicholas J.

AU - Lung, Hong Lok

AU - Wong, Ka-Leung

PY - 2021/7/26

Y1 - 2021/7/26

N2 - A lanthanide-based peptide-directed bioprobe LnP19 (Ln = Eu or Yb) is designed as an impressive example of a small molecule-based dual-functional probe for the EBV oncoprotein LMP1. The peptide P19 (Pra-KAhx-K-LDLALK-FWLY-K-IVMSDKW-K-RrRK) is designed to selectively bind to LMP1 by mimicking its TM1 region during oligomerization in lipid rafts while signal transduction is significantly suppressed. Immunofluorescence imaging and Western blotting results reveal that P19 can effectively inactivate the oncogenic cellular pathway nuclear factor κB (NF-κB) and contribute to a selective cytotoxic effect on LMP1-positive cells. By conjugation with cyclen-based europium(III) and ytterbium(III) complexes, EuP19 and YbP19 were constructed to offer visible and near-infrared LMP1-targeted imaging and cancer monitoring. In addition to the ability to target and inhibit LMP1 and to selective inhibit LMP1-positive cells, selective growth inhibition toward the LMP1-positive tumor by LnP19 is also demonstrated.

AB - A lanthanide-based peptide-directed bioprobe LnP19 (Ln = Eu or Yb) is designed as an impressive example of a small molecule-based dual-functional probe for the EBV oncoprotein LMP1. The peptide P19 (Pra-KAhx-K-LDLALK-FWLY-K-IVMSDKW-K-RrRK) is designed to selectively bind to LMP1 by mimicking its TM1 region during oligomerization in lipid rafts while signal transduction is significantly suppressed. Immunofluorescence imaging and Western blotting results reveal that P19 can effectively inactivate the oncogenic cellular pathway nuclear factor κB (NF-κB) and contribute to a selective cytotoxic effect on LMP1-positive cells. By conjugation with cyclen-based europium(III) and ytterbium(III) complexes, EuP19 and YbP19 were constructed to offer visible and near-infrared LMP1-targeted imaging and cancer monitoring. In addition to the ability to target and inhibit LMP1 and to selective inhibit LMP1-positive cells, selective growth inhibition toward the LMP1-positive tumor by LnP19 is also demonstrated.

KW - LMP1-targeted imaging EBV

KW - EBV-related cancer

KW - lanthanide(III) luminescence

KW - theranostic agent

U2 - 10.1021/jacsau.1c00187

DO - 10.1021/jacsau.1c00187

M3 - Journal article

SN - 2691-3704

VL - 1

SP - 1034

EP - 1043

JO - Journal of American Chemical Society AU

JF - Journal of American Chemical Society AU

IS - 7

ER -

Lanthanide-Based Peptide-Directed Visible/Near-Infrared Imaging and Inhibition of LMP1

Abstract

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UN SDGs

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