ICG-Loaded PEGylated BSA-Silver Nanoparticles for Effective Photothermal Cancer Therapy

Int J Nanomedicine. 2020 Jul 31:15:5459-5471. doi: 10.2147/IJN.S255874. eCollection 2020.

Abstract

Purpose: Indocyanine green (ICG), a near infrared (NIR) dye clinically approved in medical diagnostics, possesses great heat conversion efficiency, which renders itself as an effective photosensitizer for photothermal therapy (PTT) of cancer. However, there remain bottleneck challenges for use in PTT, which are the poor photo and plasma stability of ICG. To address these problems, in this research, ICG-loaded silver nanoparticles were prepared and evaluated for the applicability as an effective agent for photothermal cancer therapy.

Methods and results: PEGylated bovine serum albumin (BSA)-coated silver core/shell nanoparticles were synthesized with a high loading of ICG ("PEG-BSA-AgNP/ICG"). Physical characterization was carried out using size analyzer, transmission electron microscopy, and Fourier transform infrared spectrophotometry to identify successful preparation and size stability. ICG-loading content and the photothermal conversion efficiency of the particles were confirmed with inductively coupled plasma mass spectrometry and laser instruments. In vitro studies showed that the PEG-BSA-AgNP/ICG could provide great photostability for ICG, and their applicability for PTT was verified from the cellular study results. Furthermore, when the PEG-BSA-AgNP/ICG were tested in vivo, study results exhibited that ICG could stably remain in the blood circulation for a markedly long period (plasma half-life: 112 min), and about 1.7% ID/g tissue could be accumulated in the tumor tissue at 4 h post-injection. Such nanoparticle accumulation in the tumor enabled tumor surface temperature to be risen to 50°C (required for photo-ablation) by laser irradiation and led to successful inhibition of tumor growth in the B16F10 s.c. syngeneic nude mice model, with minimal systemic toxicity.

Conclusion: Our findings demonstrated that PEG-BSA-AgNPs could serve as effective carriers for delivering ICG to the tumor tissue with great stability and safety.

Keywords: bovine serum albumin; cancer; indocyanine green; photothermal therapy; silver nanoparticle.

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Drug Delivery Systems / methods
  • Drug Stability
  • Dynamic Light Scattering
  • Half-Life
  • Humans
  • Indocyanine Green / chemistry
  • Indocyanine Green / pharmacokinetics
  • Melanoma, Experimental / drug therapy
  • Metal Nanoparticles / chemistry*
  • Mice, Inbred ICR
  • Mice, Nude
  • Microscopy, Electron, Transmission
  • Photochemotherapy / methods*
  • Photosensitizing Agents / chemistry*
  • Polyethylene Glycols / chemistry
  • Serum Albumin, Bovine / chemistry
  • Silver / chemistry
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Antineoplastic Agents
  • Photosensitizing Agents
  • Serum Albumin, Bovine
  • Silver
  • Polyethylene Glycols
  • Indocyanine Green

Grants and funding

This work was financially supported by grants from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF- 2018R1D1A1A02047809 and 2018R1D1A1B07048818).