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Research Paper|Volume 15, Issue 11|pp 4875—4888

Co-delivery of EGCG and melittin with self-assembled fluoro-nanoparticles for enhanced cancer therapy

Meiling Sun1, Yue Wu1, Zheyu Zhou2, Siyuan Liu3, Shuai Mao1, Guoqiang Li1
  • 1Department of Hepatobiliary Surgery, Affiliate Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, Jiangsu Province, P.R. China
  • 2Department of General Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Graduate School of Peking Union Medical College Nanjing, Nanjing 210008, Jiangsu Province, P.R. China
  • 3Department of Hepatobiliary Surgery, Nanjing Medical University Nanjing, Nanjing 211166, Jiangsu Province, P.R. China
* Equal contribution
Received: March 14, 2023Accepted: May 10, 2023Published: June 5, 2023
https://doi.org/10.18632/aging.204769

Copyright: © 2023 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Purpose: Melittin (MPI) is a potential anticancer peptide due to its abilities of antitumor and immunomodulatory functions. Epigallocatechin-3-Ogallate (EGCG), a major extract of green tea, has shown great affinity for various types of biological molecules, especially for peptide/protein drugs. The aim of this study is to prepare a fluoro- nanoparticle (NP) formed by self-assembly of fluorinated EGCG (FEGCG) and MPI, and evaluate the effect of fluorine modification on MPI delivery and their synergistic antitumor effect.

Methods: Characterization of FEGCG@MPI NPs was determined by dynamic light scattering (DLS) and transmission electron microscope (TEM). Biology functions of FEGCG@MPI NPs were detected by hemolysis effect, cytotoxicity, apoptosis, cellular uptake with confocal microscopy and flow cytometry. The protein expression levels of Bcl-2/Bax, IRF, STATT-1, P-STAT-1, and PD-L1 were determined via western blotting. A transwell assay and wound healing assay were used to detect the cell migration and invasion. The antitumor efficacy of FEGCG@MPI NPs was demonstrated in a subcutaneous tumor model.

Results: Fluoro-nanoparticles could be formed by self-assembly of FEGCG and MPI, and fluorine modification on EGCG could ameliorate the side effect and delivery of MPI. The promoted therapeutics of FEGCG@MPI NPs could be achieved by regulating PD-L1 and apoptosis signaling, which might involve pathways of IRF, STAT-1/pSTAT-1, PD-L1, Bcl-2, and Bax in vitro. Moreover, FEGCG@MPI NPs could significantly inhibit the growth of tumor in vivo.

Conclusions: FEGCG@MPI NPs may offer a potential platform and promising strategy in cancer therapy.