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• W3094698532 endingPage "111442" @default.
• W3094698532 startingPage "111442" @default.
• W3094698532 abstract "• A tuftsin-based multi-target peptides (AT pep ) were successfully designed. • AT pep showed legumain-activated phagocytosis-stimulating activity. • AT pep -NPs can selectively target legumain-overexpressing TAMs and tumor cells. • Dual-targeting TAMs and cancer strategy greatly improves therapeutic efficacy. M2 tumor-associated macrophages (TAMs) play a pivotal role in cancer progression and therapy resistance. Inhibition of TAMs is of great significance to reshape the protumor environment to benefit therapeutic outcomes. In this work, we developed a novel TAMs and tumor cells dual-targeting nanoparticle (AT pep -NPs) system for cancer chemotherapy by integrating a docetaxel (DTX)-loaded nanocarrier and a multi-function peptide AT pep , which is composed of a phagocytosis-stimulating peptide-tuftsin (T pep ) fused with a substrate peptide-alanine-alanine-asparagine (AAN) of endoprotease legumain. In vitro protelytic and cellular uptake assays confirmed AT pep -NPs can be responsively activated into T pep -NPs by cleavage of legumain that is overexpressed in both tumor cells and TAMs, which then promoted tumor cells internalization and TAMs phagocytosis through neuropilin-1/Fc receptor pathways. Due to AAN deactivation effect, AT pep -NPs can effectively decrease the T pep -induced non-specific uptake by M1-polarized and normal macrophage during systemic circulation. Our results of in vivo experiments demonstrated AT pep -NPs outperformed T pep -NPs in tumor and TAMs dual-targeting delivery efficiency with markedly enhanced efficacy against both tumor growth inhibition and TAMs depletion. Overall, this study offers a novel approach for development of multitargeted delivery vehicle for improved cancer chemotherapy." @default.
• W3094698532 created "2020-11-09" @default.
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• W3094698532 date "2021-01-01" @default.
• W3094698532 modified "2023-10-17" @default.
• W3094698532 title "Legumain protease-activated tuftsin-functionalized nanoparticles for dual-targeting TAMs and cancer chemotherapy" @default.
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• W3094698532 doi "https://doi.org/10.1016/j.colsurfb.2020.111442" @default.
• W3094698532 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33166937" @default.
• W3094698532 hasPublicationYear "2021" @default.
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