Cano-Cortes, Maria VictoriaLaz-Ruiz, Jose AntonioDiaz-Mochon, Juan JoseSanchez-Martin, Rosario Maria2022-04-012022-04-012020-06-01Cano-Cortes MV, Laz-Ruiz JA, Diaz-Mochon JJ, Sanchez-Martin RM. Characterization and Therapeutic Effect of a pH Stimuli Responsive Polymeric Nanoformulation for Controlled Drug Release. Polymers. 2020 Jun 1;12(6):1265http://hdl.handle.net/10668/3515Despite 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Covalent drug conjugationTherapeutic nanodevicePolymeric nanoparticlesCancer therapyControlled drug deliverConcentración 50 InhibidoraNanopartículasConcentración de iones de hidrógenoMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Delivery Systems::Delayed-Action PreparationsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Toxicity Tests::Inhibitory Concentration 50Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic AgentsMedical Subject Headings::Technology and Food and Beverages::Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::NanoparticlesMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Hydrogen-Ion ConcentrationMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic AgentsMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell LineMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA DamageMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Alcohols::Glycols::Ethylene Glycols::Polyethylene Glycolsresearch article32492910Acceso abierto10.3390/polym120612652073-4360PMC7361709