Gold nanorod-photosensitizer conjugates with glutathione-sensitive linkages for synergistic cancer photodynamic/photothermal therapy

Biotechnol Bioeng. 2018 May;115(5):1340-1354. doi: 10.1002/bit.26536. Epub 2018 Jan 29.

Abstract

Recently, photodynamic therapy (PDT) has been intensively investigated as a useful modality for the treatment of various cancers. In addition, near infrared (NIR) photothermal therapy (PTT) using gold nanocarriers has attracted particular interest as a hyperthermia strategy. In this study, gold nanorod (AuNR)-photosensitizer conjugates with glutathione-sensitive linkages were designed for PDT and PTT. Several kinds of AuNRs with different aspect ratios were synthesized and modified with FA-conjugated block copolymers (FA-PEG-P(Asp)-DHLA) and Chlorin e6 (Ce6) as a photosensitizer. The surface-modified AuNRs showed excellent stability and solubility in aqueous solution. In particular, FA-PEG-P(Asp)-DHLA-AuNR100-SS-Ce6 with a 3.84 aspect ratio exhibited strong photothermal effects, enhanced singlet oxygen generation, and marked phototoxicity. Based on these results, we suggest that AuNR-photosensitizer conjugates with glutathione-sensitive linkages have potential application in PDT/PTT for effective clinical treatment of various cancers.

Keywords: drug delivery; gold nanorod; photodynamic therapy; photothermal therapy; targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Combined Modality Therapy / methods
  • Gold / pharmacology*
  • Humans
  • Hyperthermia, Induced / methods*
  • MCF-7 Cells
  • Models, Biological
  • Molecular Targeted Therapy / methods*
  • Nanotubes*
  • Neoplasms / therapy*
  • Photochemotherapy / methods*
  • Photosensitizing Agents / pharmacology*

Substances

  • Photosensitizing Agents
  • Gold