Size-Tunable Gd2O3@Albumin Nanoparticles Conjugating Chlorin e6 for Magnetic Resonance Imaging-Guided Photo-Induced Therapy

Theranostics. 2017 Jan 25;7(3):764-774. doi: 10.7150/thno.15757. eCollection 2017.

Abstract

Protein nanoparticles as nanocarriers are of particular interest in the field of cancer therapy. Nevertheless, so far a facile fabrication of theranostic protein nanoparticles have been explored with limited success for cancer imaging and therapy. In this work, we demonstrate the controllable synthesis of size-tunable Gd2O3@albumin conjugating photosensitizer (PS) (GA-NPs) using hollow albumin as the nanoreactor for magnetic resonance imaging (MRI)-guided photo-induced therapy. The growth of Gd2O3 nanocrystals within the hollow nanoreactors is well regulated through reaction time, and a typical PS (e.g. chlorin e6) is further conjugated with the protein corona of the nanoreactor through facile chemical coupling, followed by the formation of theranostic GA-NPs. GA-NPs exhibit good longitudinal relaxivity, ideal photostability, enhanced cellular uptakes, and preferable size-dependent tumor accumulation. Moreover, GA-NPs effectively generate remarkable photothermal effect, intracellular reactive oxygen species from Ce6, and subsequent cytoplasmic drug translocation, thereby leading to severe synergistic photothermal and photodynamic cell damages. Consequently, GA-NPs exhibit an in vivo size-dependent MRI capacity with enhanced imaging contrast for effective tumor localization, and also generate a potent synergistic photodynamic therapy/photothermal therapy efficacy under irradiation owing to their enhanced tumor accumulation and strong photo-induced cytotoxicity. These results suggest that GA-NPs can act as a promising theranostic protein nanoplatform for cancer imaging and photo-induced therapy.

Keywords: albumin nanoreactor; gadolinium oxide; magnetic resonance imaging; photodynamic therapy.; photosensitizer.

MeSH terms

  • Albumins / administration & dosage*
  • Animals
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chlorophyllides
  • Gadolinium / administration & dosage*
  • Hyperthermia, Induced / methods
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Nanoparticles / administration & dosage*
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage*
  • Porphyrins / administration & dosage*
  • Theranostic Nanomedicine / methods
  • Treatment Outcome

Substances

  • Albumins
  • Chlorophyllides
  • Photosensitizing Agents
  • Porphyrins
  • gadolinium oxide
  • phytochlorin
  • Gadolinium