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Title:
Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment | Nature Communications
Description:
Specific targeting and cellular internalization are key properties for carriers of antitumor therapeutic agents. Here, we develop a drug carrier through the attachment of substrate of endoprotease legumain, alanine–alanine–asparagine (AAN), to cell-penetrating peptides (TAT, trans-activating factor). The addition of the AAN moiety to the fourth lysine in the TAT creates a branched peptide moiety, which leads to a decrease in the transmembrane transport capacity of TAT by 72.65%. Legumain efficiently catalyses the release of TAT-liposome from the AAN-TAT-liposome and thereby recovers the penetrating capacity of TAT. Doxorubicin carried by the AAN-TAT-liposome led to an increase in the tumoricidal effect of doxorubicin and a reduction in its systemic adverse effects in comparison with doxorubicin carried by a control delivery system. Thus, the specific targeting and high efficiency of this delivery platform offers a novel approach to limit the toxicity of anticancer agents as well as increasing their efficacy in cancer therapy. Legumain is a protease found expressed in tumour cells and may be useful in the specific targeting of chemotherapeutics to tumour cells. Here, the authors design nanoparticles that are loaded with doxorubicin and contain a legumain cleavage site; once the nanoparticles enter tumour cells legumain activity results in the release of doxorubicin.
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legumain, cells, nanoparticles, tumour, cancer, article, doxorubicin, pubmed, aantatlipo, google, scholar, cas, fig, drug, breast, analysis, cell, tat, shown, results, expression, loaded, data, delivery, mouse, mice, substrate, macrophages, lysates, nature, targeting, aan, tissue, incubated, treatment, peptide, activity, liposomal, supplementary, china, usa, active, aantatlipodox, site, control, human, antibody, group, represent, model,
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nature portfolio 2-dioleoyl-sn-glycero-3-phospho-ethanolamine-n-[methoxy permissions reprints carbobenzyloxy–alanine–alanine–asparagine–ethylenediamine–etoposide privacy policy plv-ef1α-legumain-ires-bsd plasmid plv-ef1α-luciferase-ires-bsd middle line represents legumain-specific substrate ala–ala–asn author information authors jandel scientific software fitc-labelled aan-tat-lipo-dox luciferase-expressing mda-mb-231 cells fitc-labelled aan-tat-lipo nanoparticles aan-tat-lipo-dox administration group aan-tat-lipo-dox treatment group advertising nature aan-tat-lipo carrying biomacromolecules aan-tat-nanoparticles sheds light aan-tat-lipo-dox group scripps research institute aan-tat-lipo nanoparticles produced aan-tat-lipo nanoparticle structure doxorubicin-loaded aan-tat-lipo nanoparticles social media oriented central-tumor delivery aan-tat-lipo-egfp group ala–ala–asn–amc41 dir-labelled aan-tat-lipo ala–ala–asn–amc mda-mb-231 mouse model 2-dioleoyl-sn-glycero-3-phosphoethanolamine 2-dioleoyl-sn-glycero-3-phosphocholine aan-tat-lipo carrier system aan-tat-lipo enhances internalization commercial substrate z-aan-amc tat-lipo-dox experimental groups aan-tat-lipo increases accumulation cleaves aan-tat-lipo luciferase-expressing a549 cells tat-lipo-dox treatment groups luciferase-expressing 4t1 cells legumain substrate z-aan-amc japan full access establishing stable legumain-expressing aan-tan-lipo nanoparticles luciferase-expressing cell lines aan-tat-lipo-dox
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