Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Legumain protease-sheddable PEGylated, tuftsin-modified nanoparticles for selective targeting to tumour-associated macrophages
Ist Teil von
Journal of drug targeting, 2022-01, Vol.30 (1), p.82-93
Ort / Verlag
England: Taylor & Francis
Erscheinungsjahr
2022
Beschreibungen/Notizen
Tumour-associated macrophages (TAMs) represent an attractive cell target for anticancer therapy. However, selective and efficient targeting of TAMs remains difficult. Here, we constructed a novel dually functionalised nanoparticle platform (s-T
pep
-NPs) by surface co-modification of nanoparticles (NPs) with tuftsin (T
pep
) and legumain protease-sheddable polyethylene glycol 5k (PEG
5k
) to achieve selective targeted delivery to TAMs. The fluorescence resonance energy transfer experiment and in vitro cellular uptake assay confirmed that s-T
pep
-NPs can responsively shed PEG
5k
and transform into active T
pep
-NPs upon the cleavage of legumain that is overexpressed on TAM surfaces, which then promotes TAM phagocytosis through Fc receptor-mediated pathways. Owing to the shielding effect by legumain-sheddable PEG
5k
, s-T
pep
-NPs can effectively decrease the T
pep
-induced non-specific accumulation in mononuclear phagocyte system (MPS) organs during systemic circulation. Moreover, s-T
pep
-NPs can significantly enhance the tumoural accumulation and improve the specificity and efficiency of targeting to TAMs, as compared with both controls of T
pep
-NPs and non-sheddable ns-T
pep
-NPs. Overall, this study provides a robust nanoplatform with a novel avenue for improved selectivity of targeted delivery to TAMs.