ArticleMolecular pharmaceutics2025
Comparison of Micelles Single- and Dual-Targeted with Folic Acid and Biotin as the Delivery System of Docetaxel─The Influence of the Type and Amount of the Ligand on Morphology, Physicochemical Properties, and Cytotoxicity.
Article in Molecular pharmaceutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Nanoparticles (NPs) dual-targeted with folic acid (FA) and biotin (BIO) are developed to overcome problems associated with conventional chemotherapy and tumor heterogeneity. Although some preliminary studies have been conducted to develop dual-targeted micelles for delivery of docetaxel (Dtx), a more detailed analysis is needed to discover their pharmaceutical potential. Therefore, this manuscript is focused on a comprehensive analysis of the influence of the type and density of targeting ligand on micelles' morphology, physicochemical properties, drug loading and release, cell internalization, cytotoxicity in vitro against several kinds of cells and in vivo on two mice cancer models. For this purpose, three kinds of micelles were obtained: decorated with one type of ligand (FA or BIO) and dual-targeted. The micelles contained different amounts of FA- and/or BIO-functionalized polymer (10, 25, and 50%). Additionally, the dual-targeted micelles were compared with a mixture of two kinds of single-targeted micelles. The study showed that the cytotoxic effect of micelles strongly depends on the type of cancer cells and their surface characteristics. The micelles with a higher density of ligands may have higher efficiency against cells with lower expression of cell surface receptors (SK-BR-3 and MCF-7). Conversely, micelles with lower ligand density may be advantageous against cancer cells with overexpression of surface receptors (HeLa, 4T1). Interestingly, the drug delivered in FA-targeted micelles showed higher cytotoxicity compared to dual-targeted micelles in which two ligands are present on the same NP. However, Dtx delivered in a mixture of micelles single-targeted with FA and BIO showed the highest cytotoxic effect, which was confirmed in vitro and in vivo on the mice model.
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