Tetrazine-Mediated Bioorthogonal System for Prodrug Activation, Photothermal Therapy, and Optoacoustic Imaging
Nanotubes
02 engineering and technology
Antineoplastic Agents, Phytogenic
Heterocyclic Compounds, 1-Ring
Mice
Photochemotherapy
Cell Line, Tumor
Neoplasms
Animals
Humans
Camptothecin
Prodrugs
Gold
0210 nano-technology
DOI:
10.1021/acsami.9b13374
Publication Date:
2019-10-23T18:10:13Z
AUTHORS (7)
ABSTRACT
Bioorthogonal "bond cleavage" reactions hold great promise in a variety of biological applications such as controlled activation of the drug and probe, while the application of these biocompatible reactions in living animals is still in its infancy and has yet to be further explored. Herein we demonstrate a nanosized and two-component bioorthogonal system for tumor inhibition through the combined action of chemo- and photothermal therapy. The trigger of the system was fabricated by immobilizing PEGylated tetrazine on the gold nanorods, and the bioorthogonal prodrug was synthesized by caging the drug camptothecin with vinyl ether, followed by encapsulating it with phospholipid liposomes. The tetrazine-based trigger effectively mediates the bioorthogonal reaction and triggers the release of camptothecin for chemotherapy, and the gold nanorods exhibit high photothermal capability for photothermal therapy and for three-dimensional optoacoustic imaging. Upon injection into tumor-bearing mice, the two components accumulate in the tumor region and carry out a bioorthogonal reaction therein, hence releasing the parent drug. The combined actions of chemo- and photothermal therapy greatly inhibited tumor growth in mice. This strategy may afford a promising approach for achieving controlled release of an active drug in vivo through an alternative external stimulus-a bioorthogonal reaction.
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