Drug Design, Development and Therapy (Jan 2023)
Binary Nanodrug-Delivery System Designed for Leukemia Therapy: Aptamer- and Transferrin-Codecorated Daunorubicin- and Luteolin-Coloaded Nanoparticles
Abstract
Yuanyuan Zhu, Wei Zhang, Jing Chen Department of Pharmacy, Qingdao Hospital of Traditional Chinese Medicine, Qingdao Hiser Hospital Affiliated with Qingdao University, Qingdao, Shandong Province, People’s Republic of ChinaCorrespondence: Jing Chen, Department of Pharmacy, Qingdao Hospital of Traditional Chinese Medicine, Qingdao Hiser Hospital Affiliated with Qingdao University, 4 Renmin Road, Qingdao, Shandong Province, 266000, People’s Republic of China, Email [email protected]: This study aimed to develop a binary nanodrug-delivery system decorated with aptamers (APs) and transferrin (Tf) and loaded with daunorubicin (Drn) and luteolin (Lut) for the treatment of leukemia.Methods: Oligonucleotide AP- and Tf-contaiing ligands were designed and synthesized separately. AP-decorated Drn-loaded nanoparticles (AP-Drn NPs) and Tf-Lut NPs were prepared by self-assembly. An AP- and Tf-codecorated Drn- and Lut-coloaded nanodrug-delivery system (AP/Tf-Drn/Lut NPs) was prepared by self-assembly of AP-Drn NPs and Tf-Lut NPs. In vitro and in vivo efficiency of the system was evaluated on leukemia cell line and cell-bearing mouse model in comparison with single ligand–decorated, single drug–loaded and free-drug formulations.Results: AP/Tf-Drn/Lut NPs were spherical and nanosized (187.3± 5.3 nm) and loaded with about 85% of drugs. In vitro cytotoxicity of AP/Tf-Drn/Lut NPs was remarkably higher than single ligand–decorated ones. Double drug–loaded AP/Tf-Drn/Lut NPs exhibited higher tumor-cell inhibition than single drug–loaded ones, which showed a synergic effect of the two drugs. AP/Tf-Drn/Lut NPs achieved the most efficient antileukemic activity and absence of toxicity in vivo.Conclusion: The present study showed that AP/Tf-Drn/Lut NPs are a promising drug-delivery system for targeted treatment of leukemia, due to the synergic effect of the two drugs in this system. The limitations of this system include stability during large-scale production and application from bench to bedside.Keywords: acute myeloid leukemia, daunorubicin, luteolin, aptamer, transferrin, nanodrug-delivery system
