Transferrin-conjugated polymeric nanomedicine to enhance the anticancer efficacy of edelfosine in acute myeloid leukemia |
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| Institution: | 1. Nanchang University, The First Clinical Medical College, Nanchang, Jiangxi, 330006, China;2. Department of Hematology, Shandong Jining No. 1 People’s Hospital, Shandong, 272011, China;1. Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing Medical University, No. 42 Baiziting Road, Nanjing 210009, China;2. Department of Medical Oncology, First People’s Hospital of Yunnan Province, No. 175 Jinbi Road, Kunming 650032, China;1. State Civil Servant Hospital (IAMSPE), São Paulo, Brazil;2. Oncology/Hematology Discipline, ABC Medical School, Santo André, São Paulo, Brazil;3. Paulista University, São Paulo, Brazil;4. Institute of Chemical and Pharmaceutical Sciences, UNIFESP, Diadema, São Paulo, Brazil;1. Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, PMB 12003, Idi-araba, Lagos, Nigeria;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos, Lagos, Nigeria |
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| Abstract: | In this study, transferrin (Tf)-conjugated polyethylene glycol (PEG)-poly-l-lysine (PLL)-poly(lactic-co-glycolic acid) (PLGA) (PEG-PLL-PLGA)-based micellar formulations were successfully prepared for the delivery of edelfosine (EDS) in leukemia treatment. The micelles were nanosized and presented spherical shaped particles. Our in vitro data suggest that the nanoformulations maintain the biological activity of drugs for longer periods and lead to a continuous release of active drug. The enhanced cellular uptake of EDS-TM resulted in significantly higher cytotoxic effect in K562 leukemia cells. Cell cycle analysis further demonstrated the significantly higher G2/M phase arrest of cancer cells. Immunoblot analysis clearly revealed the potential of EDS-TM in inducing apoptosis of cancer cells which could improve the anticancer efficacy in leukemia. Importantly, EDS-M and EDS-TM significantly prolonged the circulation profile of EDS throughout until 24 h, indicating the potential of targeted nanoparticulate delivery system. The prolonged blood circulation potential of micellar formulations might improve the therapeutic potential of drug by increasing its bioavailability in the serum. It would be worthwhile evaluating the effects of the EDS-loaded micelles on cancer cells in vivo for clinical application. |
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| Keywords: | Leukemia Edelfosine Anticancer efficacy Apoptosis Micelles |
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