Baomin Zhu1, Huanying Zhang2, Lianling Yu3. 1. Department of Blood Transfusion, Linyi People's Hospital, Linyi, Shandong, PR China. 2. Department of Respiratory Medicine, Affiliated Hospital of Shandong Medical College, Linyi, Shandong, PR China. 3. Department of Blood Transfusion, Linyi People's Hospital, Linyi, Shandong, PR China. Electronic address: lianl_yuly@163.com.
Abstract
PURPOSE: Childhood leukemia is a common malignant disease in children. Doxorubicin (DOX) was widely used for the treatment of leukemia. However, severe toxic side effects and drug resistance are the major limitations of DOX. Nanocarriers offer the opportunity to overcome these drawbacks, there are many attempts to enhance the activity of DOX against drug resistance. This study aimed to develop a novel transferrin (Tf) modified and doxorubicin (DOX) loaded Pluronic 85/lipid-polymeric nanoparticles for the treatment of leukemia. METHODS: In this study, a novel targeted ligand: transferrin-polyethylene glycol-oleic acid (Tf-PEG-OA) was synthesized. Tf modified and DOX loaded Pluronic 85/lipid-polymeric nanoparticles (Tf-DOX P85/LPNs) were prepared via the self-assembly of PLGA, P85, stearic acid and Tf-PEG-OA using the nanoprecipitation method. The physicochemical properties of LPNs were characterized. In vitro and in vivo anti-tumor efficacy of LPNs was evaluated in human promyelocytic leukemia cell line (HL-60 cells) and DOX resistance HL-60 cell line (HL-60/DOX cells) including the relevant animal models. RESULTS: Tf-DOX P85/LPNs displayed strong anti-tumor ability on both HL-60 cells and HL-60/DOX cells than other formulations used as contrast. Also, in HL-60/DOX bearing animal models, Tf-DOX P85/LPNs exhibited the highest efficiency as well as the lowest systemic toxicity. CONCLUSION: The results indicated that Tf P85/LPNs is a promising platform to enhance efficacy, reduce toxicity and overcome drug resistance of DOX for the treatment of leukemia.
PURPOSE: Childhood leukemia is a common malignant disease in children. Doxorubicin (DOX) was widely used for the treatment of leukemia. However, severe toxic side effects and drug resistance are the major limitations of DOX. Nanocarriers offer the opportunity to overcome these drawbacks, there are many attempts to enhance the activity of DOX against drug resistance. This study aimed to develop a novel transferrin (Tf) modified and doxorubicin (DOX) loaded Pluronic 85/lipid-polymeric nanoparticles for the treatment of leukemia. METHODS: In this study, a novel targeted ligand: transferrin-polyethylene glycol-oleic acid (Tf-PEG-OA) was synthesized. Tf modified and DOX loaded Pluronic 85/lipid-polymeric nanoparticles (Tf-DOX P85/LPNs) were prepared via the self-assembly of PLGA, P85, stearic acid and Tf-PEG-OA using the nanoprecipitation method. The physicochemical properties of LPNs were characterized. In vitro and in vivo anti-tumor efficacy of LPNs was evaluated in human promyelocytic leukemia cell line (HL-60 cells) and DOX resistance HL-60 cell line (HL-60/DOX cells) including the relevant animal models. RESULTS: Tf-DOX P85/LPNs displayed strong anti-tumor ability on both HL-60 cells and HL-60/DOX cells than other formulations used as contrast. Also, in HL-60/DOX bearing animal models, Tf-DOX P85/LPNs exhibited the highest efficiency as well as the lowest systemic toxicity. CONCLUSION: The results indicated that Tf P85/LPNs is a promising platform to enhance efficacy, reduce toxicity and overcome drug resistance of DOX for the treatment of leukemia.