Eom, Taejun Yoo, Wonjae Kim, Sehoon Khan, Anzar 2024-01-19T21:30:16Z 2024-01-19T21:30:16Z 2021-09-04 2018-12 0142-9612 https://pubs.kist.re.kr/handle/201004/120646 Molecular design concepts are described for the preparation of azobenzene polymers capable of showing a tunable response to the rat liver microsome-induced side-chain self-immolation process under hypoxic conditions. It is shown that azobenzene nuclei carrying a donor/acceptor substitution pattern are the most active system towards the enzymatically triggered azobenzene cleavage reaction (half-life = t(1/12) = 6 min). Their activity is followed by azobenzene nuclei carrying donor/donor (t(1/2) = 20 min), electronically non-substituted (t(1/2) = 72 min), and acceptor (t(1/2) = 78 min) systems. This trend is preserved when a chemical stimulus, sodium dithionite, replaces the biological reducing conditions and demonstrates generality of the findings, and their potential in proteomics procedures. Furthermore, the established design concepts also permit for variation in polymer structure and topology while still maintaining the electronic substitution pattern. The steric constraints or the inherent character (hydrophilic/hydrophobic) of the azobenzene, however, does not alter the fate of the scission reaction. In all cases, the self-immolation process allows the polymer chain to convert from a chemically neutral to a cationic state. This structural transformation can be used as an activation mechanism (in vitro) to gain entry into cells through electrostatic interactions with the oppositely charged cell membrane and to deliver an anticancer drug. Interestingly, polymer structure now plays a role and bottlebrush-like copolymer show higher selectivity and faster cellular uptake. Finally, the best performing polymer allows for structural modulation into a fluorescent imaging probe. In vivo application to mice suffering from colitis confirms accumulation of the imaging probe in the diseased colon and cecum parts of the body where the endogenous microbial flora is known to produce the activation enzyme. This work, therefore, establishes general principles for the molecular design of biologically activatable and cleavable azobenzene-based polymeric scaffolds applicable to delivery and imaging applications. English ELSEVIER SCI LTD CELL-PENETRATING PEPTIDES OLIGO(ETHYLENE GLYCOL) METHACRYLATE SELF-IMMOLATIVE DENDRIMERS AZO-COUPLING REACTION TOBACCO-MOSAIC-VIRUS SURFACE MODIFICATION 2-(2-METHOXYETHOXY)ETHYL METHACRYLATE AZOREDUCTASE ACTIVITY CHEMICAL PROTEOMICS FLUORESCENT-PROBES Biologically activatable azobenzene polymers targeted at drug delivery and imaging applications Article 10.1016/j.biomaterials.2018.09.020 1 BIOMATERIALS, v.185, pp.333 - 347 BIOMATERIALS 185 333 347 scie scopus 000448494500026 2-s2.0-85054038385 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article CELL-PENETRATING PEPTIDES OLIGO(ETHYLENE GLYCOL) METHACRYLATE SELF-IMMOLATIVE DENDRIMERS AZO-COUPLING REACTION TOBACCO-MOSAIC-VIRUS SURFACE MODIFICATION 2-(2-METHOXYETHOXY)ETHYL METHACRYLATE AZOREDUCTASE ACTIVITY CHEMICAL PROTEOMICS FLUORESCENT-PROBES Polymer synthesis Reductive cleavage Activatable polymers Enzymatic reduction Self-immolative Redox active