Molecular insights for the biological interactions between polyethylene glycol and cells

As the gold standard polymer for drug delivery system, polyethylene glycol (PEG) has excellent biocompatibility. It's reported that the low nonspecific interactions between PEG and body contribute to its biocompatibility. However, here we discover dynamic biological interactions exist between PEG and cells on the molecular level. PEG (2 kD) can induce metabolism modulations and survival autophagy by creating an intracellular hypoxic environment, which act as cellular survival strategies in response to the hypoxia. In the cellular adaption process during hypoxia, PEG-treated cells decrease energy consumption by reducing cell growth rate, increase energy supply by amino acid catabolism in a short period, and survival autophagy over a relatively long period, to keep energy homeostasis and survival. Our research provides molecular insights for understanding the mechanism underlying the excellent biocompatibility of PEG, which will be of fundamental importance for further related studies on other polymers and development of polymeric materials with improved characteristics.