Synthesis and Application of Injectable Bioorthogonal Dendrimer Hydrogels for Local Drug Delivery

Leyuan Xu, Remy C. Cooper, Juan Wang, William Andrew Yeudall, Hu Yang

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

We developed novel dendrimer hydrogels (DHs) on the basis of bioorthogonal chemistry, in which polyamidoamine (PAMAM) dendrimer generation 4.0 (G4) functionalized with strained alkyne, i.e., dibenzocyclooctyne (DBCO), via a PEG spacer (Mn = 2000 g/mol) underwent strain-promoted azide-alkyne cycloaddition (SPAAC) with polyethylene glycol bisazide (PEG-BA) (Mn= 20 000 g/mol) to generate a dendrimer-PEG cross-linked network. This platform offers a high degree of functionality and modularity. A wide range of structural parameters including dendrimer generation, degree of PEGylation, loading density of clickable DBCO groups, PEG-BA chain length, as well as the ratio of clickable dendrimer to PEG-BA, and their concentrations can be readily manipulated to tune the chemical and physical properties of bioorthogonal DHs. We used this platform to prepare an injectable liquid DH. This bioorthogonal DH exhibited high cytocompatibility and enabled the sustained release of the physically loaded anticancer drug 5-fluorouracil (5-FU). Following intratumoral injection, the DH/5-FU formulation significantly suppressed tumor growth and improved the survival of HN12 tumor-bearing mice by promoting tumor cell death as well as by reducing tumor cell proliferation and angiogenesis.

Original languageEnglish (US)
Pages (from-to)1641-1653
Number of pages13
JournalACS Biomaterials Science and Engineering
Volume3
Issue number8
DOIs
Publication statusPublished - Aug 14 2017

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Keywords

  • chemotherapy
  • copper-free click chemistry
  • hydrogel
  • local drug delivery
  • nanomedicine

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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