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Dynamic Core–Shell Bioconjugates for Targeted Protein Delivery and Release
Author(s) -
Seidler Christiane,
Zegota Maksymilian Marek,
Raabe Marco,
Kuan Seah Ling,
Ng David Y. W.,
Weil Tanja
Publication year - 2018
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201800843
Subject(s) - bioorthogonal chemistry , chemistry , covalent bond , nanotechnology , nanomedicine , dynamic covalent chemistry , combinatorial chemistry , biophysics , drug delivery , phenylboronic acid , biochemistry , nanoparticle , click chemistry , materials science , molecule , organic chemistry , supramolecular chemistry , biology , catalysis
Dynamic covalent chemistry is a versatile and powerful tool that integrates both stable chemical bonds and stimulus responsiveness into the construction of smart biotherapeutics. With minimalistic molecular design, a dynamic covalent protein assembly that incorporates selective targeting and intracellular release upon pH stimulus is presented. The construct comprises an active enzymatic protein core (cytochrome c) self‐assembled with cancer cell targeting motifs (somatostatin) through boronic acid/salicylhydroxamate chemistry. The bioorthogonal assembly takes place rapidly under neutral aqueous conditions while the release of the protein is initiated under acidic conditions found within cellular vesicles during uptake. By demonstrating that these modular components act in synergy, we show the broad applicability of such chemical strategies to advance the frontier of modern nanomedicine.