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Amin, Mohamadreza; Mansourian, Mercedeh; Burgers, Peter C; Amin, Bahareh; Jaafari, Mahmoud Reza; Ten Hagen, Timo L M
Pharmaceutics, 02/2022, Letnik: 14, Številka: 2Journal Article
Modification with polyethylene glycol (PEGylation) and the use of rigid phospholipids drastically improve the pharmacokinetics of chemotherapeutics and result in more manageable or reduced side-effects. A major drawback is retarded cellular delivery of content, which, along with tumor heterogeneity, are the two main obstacles against tumor targeting. To enhance cellular delivery and reach a bigger area of a tumor, we designed liposomes decorated with two ligands: one for targeting tumor vasculature via a cyclic-pentapeptide containing arginine-glycine-aspartic acid (RGD), which impacts tumor independent of passive accumulation inside tumors, and one for extravascular targeting of tumor cells via a cell-penetrating peptide derived from human immunodeficiency virus type 1 transactivator of transcription (TAT). Liposomes with different ligand combinations were prepared and compared with respect to performance in targeting. Intravital imaging illustrates the heterogeneous behavior of RGD-liposomes in both intravascular and extravascular distribution, whereas TAT-liposomes exhibit a predictable extravascular localization but no intravascular targeting. Dual-ligand modification results in enhanced vascular targeting and a predictable extravascular behavior that improves the therapeutic efficacy of doxorubicin-loaded liposomes but also an augmented clearance rate of liposomes. However, the dual-modified liposome could be a great candidate for targeted delivery of non-toxic payloads or contrast agents for therapeutic or diagnostic purposes. Here we show that the combination of vascular-specific and tumor cell-specific ligands in a liposomal system is beneficial in bypassing the heterogeneous expression of tumor-specific markers.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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