Chaperonin-GroEL as a Smart Hydrophobic Drug Delivery and Tumor Targeting Molecular Machine for Tumor Therapy

Yi Yuan, Chong Du, Cuiji Sun, Jin Zhu, Shan Wu, Yinlong Zhang, Tianjiao Ji, Jianlin Lei, Yinmo Yang, Ning Gao, Guangjun Nie

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The targeted delivery of hydrophobic therapeutic drugs to tumors is one of the major challenges in drug development. The use of natural proteins as drug delivery vehicles holds great promise due to various functionalities of proteins. In the current study, we exploited a natural protein, GroEL, which possesses a double layer cage structure, as a hydrophobic drug container, which is switchable by ATP binding to a hydrophilic status, to design a novel and intelligent hydrophobic drug delivery molecular machine with a controlled drug release profile. When loaded with the hydrophobic antitumor drug, Doxorubicin (Dox), GroEL was able to shield the drug from the aqueous phase of blood, releasing the drug once in the presence of a critical concentration of ATP at the tumor site. Unexpectedly, we found that GroEL has a specific affinity for the cell structural protein, plectin, which is expressed at abnormally elevated levels on the membranes of tumor cells but not in normal cells. This finding, in combination with the ATP sensitivity, makes GroEL a superior natural tumor targeting nanocarrier. Our data show that GroEL-Dox is able to effectively, and highly selectively, deliver the hydrophobic drug to fast growing tumors without overt adverse effects on the major organs. GroEL is therefore a promising drug delivery platform that can overcome the obstacles to hydrophobic drug targeting and delivery.

Original languageEnglish (US)
Pages (from-to)921-928
Number of pages8
JournalNano Letters
Volume18
Issue number2
DOIs
StatePublished - Feb 14 2018

Keywords

  • ATP excitation
  • Chaperonin
  • GroEL
  • hydrophobic drug delivery
  • nanocarrier
  • tumor targeting

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

Fingerprint Dive into the research topics of 'Chaperonin-GroEL as a Smart Hydrophobic Drug Delivery and Tumor Targeting Molecular Machine for Tumor Therapy'. Together they form a unique fingerprint.

Cite this