Studies on effectiveness of PTT on 3D tumor model under microfluidic conditions using aptamer-modified nanoshells

Biosens Bioelectron. 2019 Feb 1:126:214-221. doi: 10.1016/j.bios.2018.10.069. Epub 2018 Nov 2.

Abstract

Herein, we present the research focused on the synthesis and application of aptamer-modified gold nanoshells for photothermal therapy (PTT). NIR-absorbing hollow gold nanoshells were synthetized and conjugated with anti-MUC1 aptamer (HGNs@anti-MUC1). MUC1 (Mucin 1) is a transmembrane glycoprotein, which is overexpressed in a variety of epithelial cancers (eg. breast, lung, pancreatic). In order to evaluate the efficiency of PTT with HGNs@anti-MUC1 we used 3D cell culture model - multicellular spheroids. The selected cell culture model is considered as the best in vitro model for cancer research (similar morphology, metabolite and oxygen gradients, cellular interactions and cell growth kinetics in the spheroids are similar to the early stage of a nonvascular tumor). We conducted our research on human normal (MRC-5, MCF-10A) and tumor (A549, MCF-7) cell lines using a microfluidic system. Aptamer-modified nanoparticles were accumulated selectively in tumor cells (A549, MCF-7) and this fact contributed to the reduction of tumor spheroids viability and size. It should be underlined, that it is the first example of photothermal therapy carried out in a microsystem on multicellular spheroids.

Keywords: 3D cell culture; Hollow gold nanoshells; Lab-on-a-chip; Microfluidic system; Photothermal therapy; Spheroids.

MeSH terms

  • A549 Cells
  • Aptamers, Peptide / chemistry*
  • Aptamers, Peptide / pharmacology
  • Biosensing Techniques*
  • Cell Proliferation / drug effects
  • Humans
  • MCF-7 Cells
  • Microfluidics
  • Mucin-1 / chemistry*
  • Mucin-1 / genetics
  • Nanoshells / chemistry
  • Neoplasms / diagnosis*
  • Neoplasms / pathology
  • Phototherapy
  • Spheroids, Cellular / drug effects

Substances

  • Aptamers, Peptide
  • MUC1 protein, human
  • Mucin-1