Biologically activatable azobenzene polymers targeted at drug delivery and imaging applications

Taejun Eom, Wonjae Yoo, Sehoon Kim, Anzar Khan

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 = t1/2 = 6 min). Their activity is followed by azobenzene nuclei carrying donor/donor (t1/2 = 20 min), electronically non-substituted (t1/2 = 72 min), and acceptor (t1/2 = 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.

Original languageEnglish
Pages (from-to)333-347
Number of pages15
JournalBiomaterials
Volume185
DOIs
Publication statusPublished - 2018 Dec 1

Fingerprint

Azobenzene
Drug delivery
Polymers
Imaging techniques
Pharmaceutical Preparations
Substitution reactions
Chemical activation
Dithionite
Enzyme Activation
Cecum
Liver Microsomes
Colitis
Cell membranes
Coulomb interactions
Static Electricity
Fluorescent Dyes
Human Body
Scaffolds
Liver
Proteomics

Keywords

  • Activatable polymers
  • Enzymatic reduction
  • Polymer synthesis
  • Redox active
  • Reductive cleavage
  • Self-immolative

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Biologically activatable azobenzene polymers targeted at drug delivery and imaging applications. / Eom, Taejun; Yoo, Wonjae; Kim, Sehoon; Khan, Anzar.

In: Biomaterials, Vol. 185, 01.12.2018, p. 333-347.

Research output: Contribution to journalArticle

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