Self-organized nanoparticles based on chitosan-folic acid and dextran succinate-doxorubicin conjugates for drug targeting

Abstract

Folic acid-decorated self-organized nanoparticles were fabricated to target folate receptor of cancer cells. Doxorubicin (DOX) was conjugated with carboxyl group of dextran backbone using succinic anhydride (DexSU-DOX). DOX-loaded self-organized nanoparticles were prepared by complexation with folic acid-grafted chitosan (ChitoFA) and DexSU-DOX. Nanoparticles in the aqueous environment have spherical shapes with average size less than 100 nm and their sizes were increased by coated with ChitoPEG or ChitoFA. At cell culture study with KB cells, ChitoFA coated nanoparticles (FADex NP) revealed folate-receptor mediated endocytosis to cancer cells and cell viability was significantly changed by folate receptor targeting. Tumor xenograft model of KB cells also showed similar results, i.e. FAdex NP efficiently inhibited growth of tumor compared to the treatment group with blocking of folate receptor. These results indicated that DOX-loaded nanoparticles of FADex NP are promising vehicle for anticancer drug targeting.

Design of liposomal formulations for cell targeting

“…Due to abnormal leaky (new or neo) vasculature and impaired lymphatic drainage, small non targeted particles (<400 nm) circulating in the blood tend to accumulate in the interstitial space of tumors and inflamed tis- [121][122][123][124][125][126][127][128][129][130] sues, a known hallmark of cancer (Fig. 2) [3].…”

Folic Acid Decorated Chitosan Nanoparticles and its Derivatives for the Delivery of Drugs and Genes to Cancer Cells

“…The results revealed that folic acid-dextran (FADex) nanoparticles effectively suppressed tumour growth by folate receptor targeting. These results suggested that DOX-loaded FADex nanoparticles are potential carriers for anticancer drug delivery 46 . The folate-grafted chitosan nanoparticles showed greater efficiency in cell uptake, approximately twice that of the non-folate grafted chitosan nanoparticles.…”

Folate-mediated chemotherapy and diagnostics: An updated review and outlook

“…However, the cellular uptake of FA-nanogels only reached about 50% of the initial in the presence of 0.5 mM FA and was further suppressed to 20–25% of the initial in the presence of 10 mM FA [50]. Similarly, it was shown that pre-treatment or the presence of free FA (1–2 mM) significantly reduced the cellular uptake or the cytotoxicity potency of FA-conjugated nanomedicines including FA-appended methyl-b-cyclodextrin (FA-M-β-CyD), FA-anchored cucumber mosaic virus (FA-CMV), or FA-decorated self-organized NPs (FADex NPs) [42, 47, 48]. …”