Cabazitaxel and silibinin co-encapsulated cationic liposomes for CD44 targeted delivery: A new insight into nanomedicine based combinational chemotherapy for prostate cancer - 06/01/19
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Graphical abstract |
Schematic presentation of mechanism of cabazitaxel and silibinin in prosatate cancer, specific CD44 targeted combinational cancer chemotherapy is achieved by HA coated co-loaded cationic liposomal nanocarriers of cabazitaxel and silibinin that will act on cancer cells and cancer stem cells resulting in eradication of tumor and characterisation studies of liposomal nanocarriers.
Highlights |
• | Nanomedicine based combinational chemotherapy using chemotherapeutic drug and cancer stem cell inhibitor is one of the important strategy for cancer treatment. |
• | Co-loaded liposomes of cabazitaxel (chemotherapeutic drug) and silibinin (cancer stem cell inhibitor) with specific CD44 targeting was used to eradicate cancer cells and cancer stem cells. |
• | Hyaluronic acid, a biocompatible biopolymer was used as a ligand for specific targeting of CD44 receptors over expressed on cancer stem cells. |
• | Hyaluronic acid coated liposomes for delivery of cabazitaxel and silibinin is a promising strategy for the treatment of prostate cancer. |
Abstract |
Cancer stem cells (CSCs) are the promising targets for cancer chemotherapy that cannot be eliminated by conventional chemotherapy. In this study cationic liposomes of cabazitaxel (CBX) and silibinin (SIL) were prepared with an aim to kill cancer cells and CSCs for prostate cancer. CBX act as cancer cell inhibitor and SIL as CSC inhibitor. Hyaluronic acid (HA), an endogenous anionic polysaccharide was coated on cationic liposomes for targeting CD44 receptors over expressed on CSCs. Liposomes were prepared by ethanol injection method with particle size below 100 nm and entrapment efficiency of more than 90% at 10% w/w drug loading. Liposomes were characterized by dynamic light scattering, transmission electron microscopy, 1H nuclear magnetic resonance and scanning electron microscopy-energy dispersive x-ray spectroscopy. Liposomes were evaluated for their anticancer action in androgen independent human prostate cancer cell lines (PC-3 and DU-145). HA coated liposomes showed potential cytotoxicity over other groups with low IC50, significantly inhibited cell migration and induced apoptosis. Synergistic cytotoxic effect was also observed with HA coated liposomes that resulted in colony formation inhibition and G2/M phase arrest. Proficient cytotoxicity against CD44+ cells (14.87 ± 0.41% in PC-3 and 33.95 ± 0.68% in DU-145 cells) indicated the efficiency of HA coated liposomes towards CSC targeting. Hence, the outcome of this combinational therapy with CD44 targeting indicates the suitability of HA coated CBX and SIL co-loaded liposomes as a potential approach for eradicating prostate cancer and herein might provide a insight for future studies.
Le texte complet de cet article est disponible en PDF.Abbreviations : CBX, SIL, HA, PC, CSCs, HPLC, LP, DOTAP, Chol, TPGS, AO, EB, DMSO, RPMI, FBS, PBS, PDI, CS-Sol, CS-LP, HCS-LP, IC50, CI
Keywords : Cancer stem cells, CD44 receptors, Hyaluronic acid, Cabazitaxel, Silibinin
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Vol 110
P. 803-817 - février 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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