Tumor acidic environment directs nanoparticle impacts on cancer cells

Despite impressive progress in nanotechnology-based cancer therapy being made by in vitro research, few nanoparticles (NPs) have been translated into clinical trials. The wide gap between in vitro results and nanomedicine's clinical translation might be partly due to acidic microenvironment of cancer cells being ignored in in vitro studies. To check this hypothesis, we studied the biological impacts of two dif-ferent structures of NPs on cancer cells (MDA-MB 231) at acidic (pH: 6.5) low (pH: 7) and physiological pH (pH: 7.4). We uncovered that a slight change in the pH of the cancer cell microenvironment affects the cellular uptake efficacy and toxicity mechanism of nanographene sheets and SPION@silica nanospheres. Both nanostructures exerted more substantial toxic impacts (e. g. apoptosis, necrosis, membrane disrup-tion, and oxidative stress induction) against cancer cells at physiological pH compared to acidic niche. They also differently slowed or arrested phases of the cell cycle at different pH (S and G2/M at normal pH while G0/G1 at acidic/low pH). More specifically, cancer cells expressed higher levels of interleukins involved in cancer cell resistance at acidic pH than those incubated at physiological pH. This study revealed that a slight change in extracellular pH of cancer cells could strongly affect the therapeutic/toxic impact of nanomaterials and therefore, it should be considered in the future cancer nanomedicine research.(c) 2022 Published by Elsevier Inc.

Automated summary

This study investigates the biological impacts of different nanoparticles on cancer cells at different pH levels. The researchers found that a slight change in the pH of the cancer cell microenvironment significantly affects the cellular uptake efficacy and toxicity mechanism of the nanoparticles. The nanoparticles exhibited more toxic effects against cancer cells at physiological pH compared to acidic pH, and they also affected different phases of the cell cycle at different pH levels. Additionally, cancer cells expressed higher levels of interleukins involved in cancer cell resistance at acidic pH. The findings highlight the importance of considering the extracellular pH of cancer cells in future cancer nanomedicine research.