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Two-step tumor-targeting therapy via integrating metabolic lipid-engineering with in situ click chemistry

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Abstract

Highly efficient tumor-targeted therapy remains a great challenge due to the complexity and heterogeneity of tumor tissues. Herein, we developed an in vivo two-step tumor-targeting strategy by combining metabolic lipid-engineering with a stain-promoted azide–alkyne 1,3-dipolar cycloaddition (SPAAC) reaction, independent of the tumor microenvironment and cell phenotype. Firstly, exogenously-supplied azidoethyl-cholines (AECho) were metabolically incorporated into the cell membranes in tumor tissues through the intrinsic biosynthesis of phosphatidylcholine. The pre-inserted and accumulated azido groups (N3) could subsequently serve as ‘artificial chemical receptors’ for the specific anchoring of dibenzocyclooctyne (DBCO) modified biomimetic nanoparticles (DBCO-RBCG@ICG) via in situ click chemistry, resulting in significantly enhanced tumor-targeting and then an improved photothermal therapy effect. Such a two-step targeting strategy based on these cutting-edge techniques provided new insights into the universal and precise functionalization of living tissues for site-specific drug delivery in the diagnosis and treatment of various diseases.

Graphical abstract: Two-step tumor-targeting therapy via integrating metabolic lipid-engineering with in situ click chemistry

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Article information


Submitted
16 Jan 2020
Accepted
15 Feb 2020
First published
26 Feb 2020

Biomater. Sci., 2020, Advance Article
Article type
Paper

Two-step tumor-targeting therapy via integrating metabolic lipid-engineering with in situ click chemistry

G. Lu, L. Zuo, J. Zhang, H. Zhu, W. Zhuang, W. Wei and H. Xie, Biomater. Sci., 2020, Advance Article , DOI: 10.1039/D0BM00088D

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