Synthesis and Application of Injectable Bioorthogonal Dendrimer Hydrogels for Local Drug Delivery
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.
L. Xu et al., "Synthesis and Application of Injectable Bioorthogonal Dendrimer Hydrogels for Local Drug Delivery," ACS Biomaterials Science and Engineering, vol. 3, no. 8, pp. 1641-1653, American Chemical Society (ACS), Aug 2017.
The definitive version is available at https://doi.org/10.1021/acsbiomaterials.7b00166
Chemical and Biochemical Engineering
Keywords and Phrases
chemotherapy; copper-free click chemistry; hydrogel; local drug delivery; nanomedicine
International Standard Serial Number (ISSN)
Article - Journal
© 2017 American Chemical Society (ACS), All rights reserved.
14 Aug 2017