Coating Solid Lipid Nanoparticles with Hyaluronic Acid Enhances Antitumor Activity against Melanoma Stem-like Cells

Abstract

Successful anticancer chemotherapy requires targeting tumors efficiently and further potential to eliminate cancer stem cell (CSC) subpopulations. Since CD44 is present on many types of CSCs, and it binds specially to hyaluronic acid (HA), we tested whether coating solid lipid nanoparticles with hyaluronan (HA-SLNs)would allow targeted delivery of paclitaxel (PTX) to CD44-overexpressing B16F10 melanoma cells. First, we developed a model system based on melanoma stem-like cells for experiments in vitro and in mouse xenografts, and we showed that cells expressing high levels of CD44 (CD44+) displayed a strong CSC phenotype while cells expressing low levels of CD44 (CD44-) did not. This phenotype included sphere and colony formation, higher proportion of side population cells, expression of CSC-related markers (ALDH, CD133, Oct-4) and tumorigenicity in vivo. Next we showed that administering PTX-loaded HA-SLNs led to efficient intracellular delivery of PTX and induced substantial apoptosis in CD44+ cells in vitro. In the B16F10-CD44+ lung metastasis model, PTX-loaded HA-SLNs targeted the tumor-bearing lung tissues well and subsequently exhibited significant antitumor effects with a relative low dose of PTX, which provided significant survival benefit without evidence of adverse events. These findings suggest that the HA-SLNs targeting system shows promise for enhancing cancer therapy.

Development of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose to brain delivery

“…The significant increase in particle size upon inclusion of hyaluronic acid in the aqueous phase is attributed to the hyaluronic acid coat on the particles (to be displayed in the electron microscopy pictures), in addition to the increased viscosity of the external phase of the nanoemulsion due to the presence of hyaluronic acid, leading to larger sized particles (Ibrahim et al, 2010). The increase in the negativity is also attributed to the presence of hyaluronic acid in the formulation (Shen et al, 2015).…”

Dermal delivery of doxorubicin-loaded solid lipid nanoparticles for the treatment of skin cancer

“…The topical administration of Dox-loaded SLNs for melanoma could reduce systemic side effects of Dox and increase the therapeutic effectiveness. It was reported that the small particles sizes of SLNs enhance drug penetration through the stratum corneum, the outermost layer of the epidermis which is responsible for the prevention of chemicals penetration into the skin (Kelidari et al, 2015;Shen et al, 2015). This study investigated the potential of Dox-loaded SLNs for topical delivery to the melanoma cancer induced BALB/C mice animal model.…”

CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and cancer cells using polymeric nanoparticles of salinomycin and paclitaxel

“…Coating of chitosan nanoparticles and PLGA nanoparticles with HA based on the same principle of physical adsorption, were reported in recent findings [30,53]. Shen et al also reported coating of HA onto PTX loaded solid lipid nanoparticles for enhanced anti tumor activity against melanoma stem like cells [54].…”