Cationic folate-mediated liposomal delivery of bis-arylidene oxindole induces efficient melanoma tumor regression
| Autor: | Chandra Kumar Elechalawar, Mohammed Yousuf, Rajkumar Banerjee, Abhishek Pal, Kathyayani Sridharan, Susanta Adhikari, Mohammed Tanveer Ahmed |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Indoles Melanoma Experimental Biomedical Engineering Down-Regulation Apoptosis Pharmacology Mice 03 medical and health sciences chemistry.chemical_compound Folic Acid Cell Line Tumor medicine Animals Humans Tissue Distribution General Materials Science Oxindole Caspase 8 Liposome Melanoma Folate Receptors GPI-Anchored Cancer Biological Transport Ligand (biochemistry) medicine.disease Oxindoles 030104 developmental biology chemistry Drug Resistance Neoplasm Folate receptor Liposomes Cancer cell NIH 3T3 Cells |
| Zdroj: | Biomaterials Science. 5:1898-1909 |
| ISSN: | 2047-4849 2047-4830 |
| DOI: | 10.1039/c7bm00405b |
| Popis: | The folate receptor (FR) is a well-validated and common target for cancer due to its high over-expression in many different cancer cells. Herein, we developed a new FR-targeting ligand (FA8) by conjugating folic acid and a cationic lipid. Owing to its favorable structural property FA8 as a ligand could be accommodated at an unusually higher molar ratio for a ligand-targeted liposome. We then encapsulated a drug-like molecule, bis-arylidene oxindole (NME2), in the targeted liposome. The resulting formulation induced potent caspase-8 up-regulation even in FR-moderately expressing melanoma cells. The NME2-associated non-targeted liposome (i.e., without FA8) or pristine NME2 could not up-regulate caspase-8. Caspase-8, an important apoptotic protein involved in the extrinsic pathway of apoptosis-signalling and inhibition of acquired drug resistance, was induced in cancer cells due to the combination treatment of liposomally associated FA8 and NME2 through the activation and subsequent cleavage of RIP-1. Consistently, in a melanoma tumor model too wherein FR is moderately expressed, significant tumour regression was obtained with this liposomal combination of FA8 and NME2. In conclusion, we demonstrate the development of a new FR-targeting ligand molecule whose higher level of inclusion (>10 mol%) in the liposomal formulation altered the mode of anticancer action of the encapsulated drug, thereby indicating a new therapeutic possibility involving FR targeted cancer treatment. |
| Databáze: | OpenAIRE |
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