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[Display omitted] • Synthesis and characterization of modified NH 2 -MCM-41 for drug release. • Performance of modified NH 2 -MCM-41 nanoparticles improved compared to MCM-41. • Analysis of Adriamycin, Metformin and Naproxen drugs release. The aim of this work is the preparation and characterization of modified mesoporous silica NH 2 -MCM-41 (NM-41) nanoparticles (NPs) in comparison to MCM-41 (M−41) with the aim of obtaining a pH-sensitive system for controlled drug release (CDR) applicable in cancer treatment. Three drugs were used for CDR studies including Adriamycin, Metformin and Naproxen, and loaded onto the mesoporous silica. The samples were prepared and analyzed by solid characterization methods including FTIR, XRD, SEM, TEM, BET, and DSC analyses. The SEM images clearly showed the increase in surface porosity of NM-41 nanocarriers (NCs) compared to M−41 NCs. The CDR behavior of the obtained NCs was investigated at pH 1.5–3.5 (simulated gastric fluid media-SGF), pH 6 (simulated intestine fluid media-SIF) and pH 7.35–7.45 (simulated body fluid media-SBF). The results showed that the performance of modified NM-41 NPs improved compared to M−41, and the performance of modified NM-41 NPs at SIF and SBF pHs is much higher than SGF, which shows the success in the preparation of drug pH-sensitive NCs for CDR. The results of drug loading showed that the amount of Adriamycin, Metformin and Naproxen drugs in modified NM-41 NPs is significantly higher than M−41. Furthermore, survival studies were conducted for the prepared systems and the results showed good biocompatibility of the prepared drug delivery systems (DDS). [ABSTRACT FROM AUTHOR]