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Sialic Acid-anchored Micelles: a Hierarchical Targeting Device for Enhanced Tumor Tissue Accumulation and Cellular Internalization.

08:00 EDT 15th August 2018 | BioPortfolio

Summary of "Sialic Acid-anchored Micelles: a Hierarchical Targeting Device for Enhanced Tumor Tissue Accumulation and Cellular Internalization."

Targeted Drug Delivery Systems (TDDS) have attracted wide attention with reduced drug side effects and improved anti-tumor efficacy in comparison with traditional preparations. While targeting moiety in existing TDDS principally focused on recognition of receptors on the surface of tumor cells, accumulation into tumor tissue only could be performed by enhanced permeability and retention effect and active transportation into tumor cells. Doxorubicin (DOX)-loaded sialic acid-dextran (Dex)-octadecanoic acid (OA) micelles (SA-Dex-OA/DOX) were designed for targeting hepatocellular carcinoma effectively. The synthesized conjugates could self-aggregate to form micelles with a critical micelle concentration of 27.6 μg·mL-1 and diameter of 54.53±3.23 nm. SA-Dex-OA micelles incorporated with 4.36% DOX loading content could prolong in vitro drug release to 96 h with 80 % of final release. Cellular transportation studies revealed that SA-Dex-OA micelles mediated more efficient DOX delivery into Bel-7402 cells than those without SA modification. In vivo biodistribution test demonstrated that SA-Dex-OA/ICG micelles showed 3.05-fold higher accumulation into Bel-7402 tumors. The recognition of overexpressed E-selectin in inflammatory tumor vascular endothelial cells led to large accumulation of SA-Dex-OA/ICG micelles into tumor tissue, and the E-selectin upregulated on the surface of tumor cells contributed to active cellular transportation into tumor cells. Accordingly, SA-Dex-OA/DOX exhibited prior suppression on Bel-7402 tumor growth to Dex-OA/DOX micelles and free DOX (the tumor inhibition: 79.2 % vs 61.0 % and 51.3%). These results suggest that SA-functionalized micelles with dual targeting properties has high potential for liver cancer therapy.

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Name: Molecular pharmaceutics
ISSN: 1543-8392
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