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Zha, Shuai; Chau, Ho‐Fai; Chau, Wai Yin; Chan, Lai Sheung; Lin, Jun; Lo, Kwok Wai; Chi‐Shing Cho, William; Yip, Yim Ling; Tsao, Sai Wah; Farrell, Paul J.; Feng, Liang; Di, Jin Ming; Law, Ga‐Lai; Lung, Hong Lok; Wong, Ka‐Leung
Advanced science, 03/2021, Letnik: 8, Številka: 5Journal Article
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. The upconversion nanoplatform with desired responsiveness toward tumor microenvironment is introduced. Thereafter, EBV‐cancer model is used to investigate by utilizing the safe nanoplatform via targeting LMP1 and EBNA1 with responsive emission, satisfactory prohibitive performances are observed in vitro and in vivo, thanks to the specific dual‐targeting peptides. This proposed multifunctional nanoplatform can achieve both monitoring and treatment for EBV cancer.
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in: SICRIS
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