Structural and Functional Characterizations of Cancer Targeting Nanoparticles Based on Hepatitis B Virus Capsid

Yunseok Heo, Hyeongseop Jeong, Youngki Yoo, Ji Hye Yun, Bumhan Ryu, Young Je Cha, Bo Ram Lee, Ye Eun Jeon, Jongmin Kim, Sojin Jeong, Eunji Jo, Jae Sung Woo, Jeewon Lee, Hyun Soo Cho, Weontae Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Cancer targeting nanoparticles have been extensively studied, but stable and applicable agents have yet to be developed. Here, we report stable nanoparticles based on hepatitis B core antigen (HBcAg) for cancer therapy. HBcAg monomers assemble into spherical capsids of 180 or 240 subunits. HBcAg was engineered to present an affibody for binding to human epidermal growth factor receptor 1 (EGFR) and to present histidine and tyrosine tags for binding to gold ions. The HBcAg engineered to present affibody and tags (HAF) bound specifically to EGFR and exterminated the EGFR-overexpressing adenocarcinomas under alternating magnetic field (AMF) after binding with gold ions. Using cryogenic electron microscopy (cryo-EM), we obtained the molecular structures of recombinant HAF and found that the overall structure of HAF was the same as that of HBcAg, except with the affibody on the spike. Therefore, HAF is viable for cancer therapy with the advantage of maintaining a stable capsid form. If the affibody in HAF is replaced with a specific sequence to bind to another targetable disease protein, the nanoparticles can be used for drug development over a wide spectrum.

Original languageEnglish
JournalInternational journal of molecular sciences
Volume22
Issue number17
DOIs
Publication statusPublished - 2021 Aug 24

Keywords

  • affibody
  • cancer therapy
  • cryo-EM
  • EGFR
  • gold ions
  • HBcAg

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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