ROS-responsive selenium-containing polyphosphoester nanogels for activated anticancer drug release

Nowadays, the stability and on-demand release of drug carriers are still to be solved. To meet the demand of these issues, we developed a reactive oxygen species (ROS) responsive selenium-containing polyphosphoesters nanogel (PSeP) by a facile one-step ring-opening polymerization of the novel monomer 4-selenoctane-1,8-diyl bis(propylphosphatelane) (Se-COP) with polyethylene glycol (mPEG) employed as the macroinitiator. Their structure was confirmed by NMR, FT-IR and GPC. The crosslinked core-shell structure imparted the nanogels with excellent dimensional stability according to the dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, the selenide groups endowed the nanogels with rich ROS responsiveness when subjected to the stimuli of H 2 O 2 , thus the drug-loaded PSeP nanogels displayed swollen behaviors leading to an activated doxorubicin hydrochloride (DOX · HCl) release. The release mechanisms fitted by the Ritger-Peppas power-law model also proved the swollen release process. MTT assays exhibited that the PSeP nanogels were nontoxic up to a tested concentration of 50 μg mL −1  by A549 and HEK293, and the DOX-loaded PSeP had a high anti-cancer behaviour against A549 cancer cells. Additionally, these nanogels possessed enhanced intracellular drug release by CLSM . Therefore, these results highlighted that the selenium-containing polyphosphoesters nanogels could be a potential platform for the ROS-sensitive drug delivery.