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Title: Dual-Responsive Polyphosphoester-Doxorubicin Prodrug Containing a Diselenide Bond: Synthesis, Characterization, and Drug Delivery. Author: Ma G, Liu J, He J, Zhang M, Ni P. Journal: ACS Biomater Sci Eng; 2018 Jul 09; 4(7):2443-2452. PubMed ID: 33435108. Abstract: The development of novel stimuli-responsive and biodegradable polyphosphoester-anticancer prodrugs is of importance in designing water-soluble prodrugs utilized in the field of drug delivery. In this study, the focus is on the synthesis of biocompatible and biodegradable diselenide-containing polyphosphoester [PEEP-b-PBYP-Se]2 using reduction-responsive di(1-hydroxylundecyl) diselenide as an initiator to polymerize 2-(but-3-yn-1-yloxy)-2-oxo-1,3,2-dioxaphospholane (BYP) and 2-ethoxy-2-oxo-1,3,2-dioxaphospholane (EOP). After that, a doxorubicin (DOX) derivative containing an azide group was linked onto the side chain of [PEEP-b-PBYP-Se]2 via the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction to yield a pH/reduction-responsive polymeric prodrug, namely [PEEP-b-(PBYP-hyd-DOX)-Se]2. The chemical structures of various polymers were characterized by nuclear magnetic resonance spectroscopy, ultraviolet-visible spectrophotometer, Fourier transform infrared spectroscopy, and high-performance liquid chromatography. The self-assembly behavior measured by dynamic light scattering and transmission electron microscopy clearly supported the formation of the prodrug nanoparticles (NPs). The results indicated that the polymeric prodrug NPs were relatively uniform spheres that could maintain stability in a physiological condition but be cleaved in acidic or reductive medium. Furthermore, the pH- and reduction-responsive properties of the prodrug NPs were investigated via drug release in vitro in different media. It turned out that the drug was efficiently released in acidic or reductive medium compared with that under physiological conditions. The results of methyl thiazolyl tetrazolium assays confirmed the favorable biocompatibility of [PEEP-b-PBYP-Se]2. Moreover, the cell cytotoxicity and intracellular uptake experiments were carried out to verify the efficient cellular proliferation inhibition. This finding contributes to the design of a novel diselenide-containing polyphosphoester-doxorubicin prodrug.[Abstract] [Full Text] [Related] [New Search]