Gold nanoparticle mediated radiation response among key cell components of the tumour microenvironment for the advancement of cancer nanotechnology.

Scientific Reports
Kyle BrommaDevika B Chithrani

Abstract

One of the major issues in cancer radiotherapy (RT) is normal tissue toxicity. Introduction of radiosensitizers like gold nanoparticles (GNPs) into cancer cells to enhance the local RT dose has been tested successfully. However, it is not known how GNPs interact with other stromal cells such as normal fibroblasts (FBs) and cancer associated fibroblasts (CAFs) within the tumour microenvironment. It is known that FBs turn into CAFs to promote tumour growth. Hence, we used FBs and CAFs along with HeLa (our cancer cell line) to evaluate the differences in GNP uptake and resulting radiation induced damage to elucidate the GNP-mediated therapeutic effect in RT. The CAFs had the largest uptake of the GNPs per cell, with on average 265% relative to HeLa while FBs had only 7.55% the uptake of HeLa and 2.87% the uptake of CAFs. This translated to increases in 53BP1-related DNA damage foci in CAFs (13.5%) and HeLa (9.8%) compared to FBs (8.8%) with RT treatment. This difference in DNA damage due to selective targeting of cancer associated cells over normal cells may allow GNPs to be an effective tool in future cancer RT to battle normal tissue toxicity while improving local RT dose to the tumour.

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Citations

Feb 12, 2021·The Science of the Total Environment·Rawil FakhrullinGölnur Fakhrullina
Feb 20, 2021·International Journal of Nanomedicine·Liuyun GongSuxia Han
Mar 27, 2021·Physica Medica : PM : an International Journal Devoted to the Applications of Physics to Medicine and Biology : Official Journal of the Italian Association of Biomedical Physics (AIFB)·H RabusH Nettelbeck
Aug 17, 2021·Frontiers in Public Health·Charnay CunninghamCharlot Vandevoorde

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Methods Mentioned

BETA
dynamic light scattering
surface plasmon resonance
confocal microscopy
transfection

Software Mentioned

CytoViva
GraphPad Prism
ImageJ

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