Fluorescence guided photothermal/photodynamic ablation of tumours using pH-responsive chlorin e6-conjugated gold nanorods

Colloids Surf B Biointerfaces. 2017 Dec 1:160:345-354. doi: 10.1016/j.colsurfb.2017.09.045. Epub 2017 Sep 21.

Abstract

Photothermal/photodynamic therapies (PTT/PDT) have been widely accepted as non-invasive therapeutic modalities to erase tumours. However, both therapies face the problem of precisely locating tumours and reducing their side effects. Herein, chlorin e6 conjugated gold nanorod, (Ce6-PEG-AuNR), a type of gold nanorod-photosensitizer conjugate, is designed as a kind of nano-therapeutic agent to simultaneously realize combined PTT/PDT. Compared to free Ce6, the fluorescence of Ce6 adhered to the conjugate is effectively quenched by the longitudinal surface plasmon resonance (LSPR) of in the Ce6-PEG-AuNR. However, the specific fluorescence of Ce6 can be recovered in tumour tissue when Ce6 is separated from the conjugate owing to the cleavage of hydrazone bond between Ce6 and PEG caused by intracellular acidic conditions in tumour tissue. Based on this effect, we can precisely locate tumours and further kill cancer cells by combined PTT/PDT. In addition, the combined therapy (PTT/PDT) function is more efficient in cancer treatment than that of PTT or PDT alone. Therefore, Ce6-PEG-AuNR can serve as a promising dual-modal phototherapeutic agent as well as a tumour-sensitive fluorescent probe to diagnose and treat cancer.

Keywords: Ce6; Fluorescence; Gold nanorod; Photodynamic therapy; Photothermal therapy.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Chlorophyllides
  • Female
  • Fluorescence
  • Gold / chemistry*
  • HeLa Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Electron, Transmission
  • Nanotubes / chemistry*
  • Nanotubes / ultrastructure
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Photochemotherapy / methods*
  • Porphyrins / chemistry
  • Porphyrins / pharmacokinetics
  • Porphyrins / pharmacology*
  • Radiation-Sensitizing Agents / chemistry
  • Radiation-Sensitizing Agents / pharmacokinetics
  • Radiation-Sensitizing Agents / pharmacology
  • Reactive Oxygen Species / metabolism
  • Tissue Distribution
  • Xenograft Model Antitumor Assays / methods*

Substances

  • Chlorophyllides
  • Porphyrins
  • Radiation-Sensitizing Agents
  • Reactive Oxygen Species
  • phytochlorin
  • Gold