To the best of our knowledge, the present study is the first to statement of the potent activity of salinomycin against ovarian CSCs
To the best of our knowledge, the present study is the first to statement of the potent activity of salinomycin against ovarian CSCs. Although salinomycin has proven potent activity against ovarian CSCs, it has poor water solubility and low bioavailability. bound to CD133+ ovarian malignancy cells, resulting in an increased cytotoxic effect in CD133+ ovarian malignancy cells, compared with the untargeted SAL-NPs and salinomycin. CD133-SAL-NPs reduced the percentage of CD133+ ovarian CSCs in ovarian cells more effectively than treatment with salinomycin or SAL-NPs, suggesting that CD133-SAL-NP targeted CD133+ ovarian CSCs. In nude mice bearing ovarian malignancy xenografts, CD133-SAL-NPs exerted improved restorative effects compared with SAL-NPs and salinomycin. Thus, CD133 was demonstrated to be a encouraging target for drug HG6-64-1 delivery to ovarian CSCs, and may become useful as an agent to inhibit the growth of ovarian malignancy by focusing on CD133+ ovarian CSCs. CD133-SAL-NPs HG6-64-1 may consequently represent a encouraging approach for the treatment of ovarian malignancy. (1) used a murine model to demonstrate that CD133+ ovarian malignancy cells have similar characteristics to ovarian CSCs in terms of self-renewal, differentiation and tumorigenicity. Gupta (9) screened a series of chemicals to discover compounds that selectively target and inhibit breast CSCs, and proven that salinomycin, a polyether ionophore antibiotic, selectively inhibited CSCs and exerted potent effects against various types of CSC (9). The mechanisms underlying the anti-CSC activity of salinomycin include inhibition of the differentiation of CSCs, the Wnt/-catenin pathway and autophagy (9,10). These results suggest that salinomycin represents a encouraging agent capable of focusing on CSCs. To the best of our knowledge, no previous reports have investigated the therapeutic effectiveness of salinomycin against ovarian CSCs. Therefore, it is necessary to explore the restorative HG6-64-1 effectiveness of salinomycin against ovarian CSCs. There is another important issue with respect to salinomycin, which has to be resolved prior to medical software. Owing to its poor water solubility, salinomycin must be dissolved in ethanol prior to administration (11,12). Nanoparticles have emerged like a encouraging approach to improve the solubility of salinomycin (5,6). Several salinomycin-loaded nanoparticles have been developed for its delivery to CSCs, and these have achieved an improved therapeutic effect over free salinomycin (13,14). Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are widely used because of the security record in humans (15,16). PLGA nanoparticles are frequently revised with poly(ethylene glycol) (PEG) to increase their blood circulation. The PEGylation of nanoparticles significantly increases their passive HG6-64-1 focusing on of tumors (15). Considerable interest has been generated in antibody-conjugated nanoparticles, as these are widely used as targeted drug delivery systems (17). Several antibodies, including anti-human epidermal growth element receptor 2 (HER2) or anti-epidermal growth element receptor (EGFR) antibodies, have been used to promote the delivery of small interfering RNA nanoparticles to EGFR-overexpressing or HER2-overexpressing cancers (18,19). As cluster of differentiation (CD)133 is considered to be a marker for ovarian CSCs, our group hypothesized that this CD133 antibody may be able to promote the salinomycin delivery of nanoparticles to CD133-overexpressing ovarian CSCs. In the present study, the CSC-like properties of purified CD133+ cells from your OVCAR-3 and PA-1 ovarian malignancy cell lines were exhibited. Subsequently, salinomycin-loaded PLGA nanoparticles conjugated with CD133 antibodies (CD133-SAL-NP) were developed to target CD133+ ovarian CSCs. Materials and methods Materials Poly(lactide-co-glycolide)-b-poly(ethylene glycol)-COOH endcap (PLGA-PEG-COOH; ~17,000 Da, 3,400 Da) was purchased from Akina, Inc. (West Lafayette, IN, USA). Phycoerythrin (PE)-conjugated CD133 antibodies (cat. no. 130080801) HG6-64-1 and the CD133 MicroBead kit were provided by Miltenyi Biotec, Inc. (Auburn, CA, USA). CD133 antibodies were purchased from R&D Systems, Inc. (cat. no. MAB11331; Minneapolis, MN, USA). Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), B-27, insulin-transferrin-selenium (ITS), and TRIzol reagent Mmp7 were provided by Thermo Fisher Scientific, Inc. (Waltham, MA, USA). N-hydroxysuccinimide (NHS), 1-ethyl-3-3-dimethylaminopropyl carbodiimide (EDC), salinomycin, coumarin 6 and all analytical grade organic reagents were purchased from Sigma-Aldrich; Merck KGaA (Darmstadt, Germany). Cell Counting Kit-8 was purchased from Dojindo Molecular Technologies, Inc. (Kumamoto, Japan), and the Reverse Transcription System kit was provided by Promega Corporation (Madison, WI, USA). Cells and culture The OVCAR-3 and PA-1 ovarian.