Galectin-1-based tumour-targeting for gold nanostructure-mediated photothermal therapy

Abstract

Purpose: To demonstrate delivery of Au nanocages to cells using the galectin-1 binding peptide anginex (Ax) and to demonstrate the value of this targeting for selective in vitro photothermal cell killing.

Materials and methods: Au nanocages were synthesised, coated with polydopamine (PDA), and conjugated with Ax. Tumour and endothelial cell viability was measured with and without laser irradiation. Photoacoustic (PA) mapping and PA flow cytometry were used to confirm cell targeting in vitro and in tissue slices ex vivo.

Results: Cell viability was maintained at ≥50% at 100 pM suggesting low toxicity of the nanocage alone. Combining the targeted construct (25 pM) with low power 808 nm laser irradiation for 10–20 min (a duration previously shown to induce rapid and sustained heating of Au nanocages [AuNC] in solution), resulted in over 50% killing of endothelial and tumour cells. In contrast, the untargeted construct combined with laser irradiation resulted in negligible cell killing. We estimate approximately 6 × 10⁴ peptides were conjugated to each nanocage, which also resulted in inhibition of cell migration. Binding of the targeted nanocage reached a plateau after three hours, and cell association was 20-fold higher than non-targeted nanocages both in vitro and ex vivo on tumour tissue slices. A threefold increase in tumour accumulation was observed in preliminary in vivo studies.

Conclusions: These studies demonstrate Ax’s potential as an effective targeting agent for Au-based theranostics to tumour and endothelial cells, enabling photothermal killing. This platform further suggests potential for multimodal in vivo therapy via next-generation drug-loaded nanocages.

Keywords:

• Targeted nanomedicine
• breast cancer
• photothermal
• photoacoustic microscopy
• gold nanocage

Acknowledgments

We thank Prof. M.S. Smeltzer, PhD for supplying the diode laser for these studies. We also thank E. Pollack and B. Shaulis for help with the ICP-MS study at the Arkansas Mass Spectrometry facility, which is supported by the Arkansas Biosciences Institute.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This research was supported in part by a grant from the Arkansas Breast Cancer Research Programs and the Winthrop P. Rockefeller Cancer Institute, as well as by NIH grants R01CA131164 and R01EB017217, NSF grants OIA 1457888 and DBI 1556068, and the Translational Research Institute at UAMS.