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.
Highlights
One of the major issues in cancer radiotherapy (RT) is normal tissue toxicity
While the introduction of targeting methods such as volumetric modulated arc therapy (VMAT) and image guided radiotherapy (IGRT) has improved the efficacy of RT, there is a limit of improvement when it comes to the use of RT as a singular treatment m odality[9]
The efficacy of UV–VIS for measurement of gold nanoparticles (GNPs) concentration was independently verified through the use of inductively coupled plasma mass spectrometry (ICP-MS), which found that a concentration of 0.2 nM from UV–VIS led to a measured concentration of 0.204 nM
Summary
Introduction of radiosensitizers like gold nanoparticles (GNPs) into cancer cells to enhance the local RT dose has been tested successfully 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. 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. This study aims to investigate the GNP-mediated radiation sensitization in three main interrelated cell components in TME as illustrated in the thematic Fig. 1A
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