RT Journal Article T1 Characterization and Therapeutic Effect of a pH Stimuli Responsive Polymeric Nanoformulation for Controlled Drug Release. A1 Cano-Cortes, Maria Victoria A1 Laz-Ruiz, Jose Antonio A1 Diaz-Mochon, Juan Jose A1 Sanchez-Martin, Rosario Maria K1 cancer therapy K1 controlled drug delivery K1 covalent drug conjugation K1 polymeric nanoparticles K1 therapeutic nanodevice AB Despite the large number of polymeric nanodelivery systems that have been recently developed, there is still room for improvement in terms of therapeutic efficiency. Most reported nanodevices for controlled release are based on drug encapsulation, which can lead to undesired drug leakage with a consequent reduction in efficacy and an increase in systemic toxicity. Herein, we present a strategy for covalent drug conjugation to the nanodevice to overcome this drawback. In particular, we characterize and evaluate an effective therapeutic polymeric PEGylated nanosystem for controlled pH-sensitive drug release on a breast cancer (MDA-MB-231) and two lung cancer (A549 and H520) cell lines. A significant reduction in the required drug dose to reach its half maximal inhibitory concentration (IC50 value) was achieved by conjugation of the drug to the nanoparticles, which leads to an improvement in the therapeutic index by increasing the efficiency. The genotoxic effect of this nanodevice in cancer cells was confirmed by nucleus histone H2AX specific immunostaining. In summary, we successfully characterized and validated a pH responsive therapeutic polymeric nanodevice in vitro for controlled anticancer drug release. YR 2020 FD 2020-06-01 LK https://hdl.handle.net/10668/28419 UL https://hdl.handle.net/10668/28419 LA en DS RISalud RD Apr 12, 2025