Effective and Selective Anti-Cancer Protein Delivery via All-Functions-in-One Nanocarriers Coupled with Visible Light-Responsive, Reversible Protein Engineering

Hua He, Yongbing Chen, Yongjuan Li, Ziyuan Song, Yinan Zhong, Rongying Zhu, Jianjun Cheng, Lichen Yin

Research output: Contribution to journalArticle

Abstract

Efficient intracellular delivery of protein drugs and tumor-specific activation of protein functions are critical toward anti-cancer protein therapy. However, an omnipotent protein delivery system that can harmonize the complicated systemic barriers as well as spatiotemporally manipulate protein function is lacking. Herein, an “all-functions-in-one” nanocarrier doped with photosensitizer (PS) is developed and coupled with reactive oxygen species (ROS)-responsive, reversible protein engineering to realize cancer-targeted protein delivery, and spatiotemporal manipulation of protein activities using long-wavelength visible light (635 nm) at low power density (5 mW cm−2). Particularly, RNase A is caged with H2O2-cleavable phenylboronic acid to form 4-nitrophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl carbonate (NBC)-modified RNase (RNBC), which is encapsulated in acid-degradable, ketal-crosslinked PEI (KPEI)-based nanocomplexes (NCs) coated with PS-modified hyaluronic acid (HA). Such NCs harmonize the critical processes for protein delivery, wherein HA coating renders NCs with long blood circulation and cancer cell targeting, and KPEI enables endosomal escape as well as acid-triggered intracellular RNBC release. Tumor-specific light irradiation generates H2O2 to kill cancer cells and restore the protein activity, thus achieving synergistic anti-cancer efficacy. It is the first time to photomanipulate protein functions by coupling ROS-cleavable protein caging with PS-mediated ROS generation, and the “all-functions-in-one” nanocarrier represents a promising example for the programmed anti-cancer protein delivery.

Original languageEnglish (US)
Article number1706710
JournalAdvanced Functional Materials
Volume28
Issue number14
DOIs
StatePublished - Apr 5 2018

Keywords

  • ROS responsiveness
  • cancer therapy
  • intracellular protein delivery
  • light responsiveness
  • protein caging

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

Fingerprint Dive into the research topics of 'Effective and Selective Anti-Cancer Protein Delivery via All-Functions-in-One Nanocarriers Coupled with Visible Light-Responsive, Reversible Protein Engineering'. Together they form a unique fingerprint.

  • Cite this