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• W3014625810 abstract "Nanoparticles (NPs), such as liposomes, effectively evade the severe toxicity of unexpected accumulation and passively shuttle drugs into tumor tissues by enhanced permeability and retention. In the case of non-small cell lung cancer and pancreatic ductal adenocarcinoma, cancer-associated fibroblasts promote the aggregation of a gel-like extracellular matrix that forms a physical barrier in the desmoplastic stroma of the tumor. These stroma are composed of protein networks and glycosaminoglycans (GAGs) that greatly compromise tumor-penetrating performance, leading to insufficient extravasation and tissue penetration of NPs. Moreover, the presence of heparan sulfate (HS) and related proteoglycans on the cell surface and tumor extracellular matrix may serve as molecular targets for NP-mediated drug delivery. Here, a GAG-binding peptide (GBP) with high affinity for HS and high cell-penetrating activity was used to develop an HS-targeting delivery system. Specifically, liposomal doxorubicin (L-DOX) was modified by post-insertion with the GBP. We show that the in vitro uptake of L-DOX in A549 lung adenocarcinoma cells increased by GBP modification. Cellular uptake of GBP-modified L-DOX (L-DOX-GBP) was diminished in the presence of extracellular HS but not in the presence of other GAGs, indicating that the interaction with HS is critical for the cell surface binding of L-DOX-GBP. The cytotoxicity of doxorubicin positively correlated with the molecular composition of GBP. Moreover, GBP modification improved the in vivo distribution and anticancer efficiency of L-DOX, with enhanced desmoplastic targeting and extensive distribution. Taken together, GBP modification may greatly improve the tissue distribution and delivery efficiency of NPs against HS-abundant desmoplastic stroma-associated neoplasm." @default.
• W3014625810 created "2020-04-10" @default.
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• W3014625810 date "2020-01-01" @default.
• W3014625810 modified "2023-10-10" @default.
• W3014625810 title "Heparan sulfate targeting strategy for enhancing liposomal drug accumulation and facilitating deep distribution in tumors" @default.
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• W3014625810 doi "https://doi.org/10.1080/10717544.2020.1745326" @default.
• W3014625810 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7170378" @default.
• W3014625810 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32241176" @default.
• W3014625810 hasPublicationYear "2020" @default.
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