Mixed Micelles for Targeted and Efficient Doxorubicin Delivery to Multidrug‐Resistant Breast Cancer Cells

Abstract

For efficient treatment of multidrug-resistance (MDR) breast cancer cells, design of biocompatible mixed micelles with diverse functional moieties and superior stability is needed for targeted delivery of chemical drugs. In this study, polypropylene glycol (PPG)-grafted hyaluronic acid (HA) copolymers (PPG-g-HA) are used to make mixed micelles with different amounts of pluronic L61, named PPG-g-HA/L61 micelles. Optimized PPG-g-HA/L61 micelles with 3% pluronic L61 exhibit great stability in aqueous solution, superior biocompatibility, and significantly increased uptake into MCF-7 MDR cells via HA-CD44-specific interactions when compared to free doxorubicin (DOX) and other types of micelles. In addition, DOX in PPG-g-HA/L61 micelles with 3% pluronic L61 have toxicity in MCF-7 MDR cells but significantly lower toxicity in fibroblast L929 cells compared to free DOX. Thus, PPG-g-HA/L61 micelles with 3% pluronic L61 content can be a promising nanocarrier to overcome MDR and release DOX in a hyaluronidase-sensitive manner without any toxicity to normal cells.

I-motif-coated exosomes as a pH-sensitive carrier for anticancer drugs

“…Dox fluorescent signal at dsi-motif/Dox molar ratio of 1:1 was significantly reduced below 10% both at 24°C and at 37°C. More than 90% of initial Dox was intercalated within ds-i-motif, which is consistent to previous studies [17,18,22,24]. In this study, we used a one base pair mismatched DNA sequence (flare) as a complementary sequence for the i-motif.…”

“…Multi-drug-resistant breast cancer cells of the MCF-7 (MCF-7/MDR) cell line were maintained in RPMI 1640 supplemented with 10% FBS, 100 U/mL penicillin, and 100 lg/mL streptomycin at 37°C in a humidified atmosphere of 5% CO 2 , according to our previous study [22]. For the anti-proliferation study, cells were seeded at a density of 1 9 10 4 cells per well in a 96-well plate 24 h before treatment.…”

GLUT1‐Targeting and GSH‐Responsive DOX/L61 Nanodrug Particles for Enhancing MDR Breast Cancer Therapy

“…Past studies have shown that DOX not only inhibited DNA synthesis but also produced cytotoxic hydroxyl radicals. [ 19 ] Thus, intracellular ROS levels were further assessed by 2,7‐Dichlorodi‐hydrofluorescein diacetate (DCFH‐DA) probe. As shown in Figure a, bright green fluorescence was observed in MCF‐7 cells with treatment of free DOX or DOX‐NPs, indicating ROS generation.…”

Recent advances in hyaluronic acid-decorated nanocarriers for targeted cancer therapy

“…Therefore, PPG-g-HA/L61 micelles were the most selective cytotoxic delivery system tested by Jung et al for the selective treatment of cancer cells. Furthermore, by mixing the functional pluronic L61 polymer with CD44-targeted PPG-g-HA copolymers, Jung et al were able to create a novel formulation that utilizes both the targeting strategy of HA and the ability of pluronic L61 to combat MDR cancers via ATP depletion [102]. …”