Binary Nanodrug-Delivery System Designed for Leukemia Therapy: Aptamer- and Transferrin-Codecorated Daunorubicin- and Luteolin-Coloaded Nanoparticles

Abstract

Objective 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.

Aptamers for the Delivery of Plant-Based Compounds: A Review

“…To perform that, anionic nanoparticles decorated with transferrin and loaded with luteolin, along with cationic nanoparticles decorated with the aptamer and loaded with daunorubicin, were prepared separately. Subsequently, the Apt/Tf-Dn/LUT delivery system was obtained through self-assembly, facilitated by electronic interaction [ 149 ].…”

“…The modified amino group of CD 117 aptamer was covalently bound to the carboxylic group of PEG-COOH through the NHS protocol [ 149 ]. The sequence of this aptamer consists of 35 oligonucleotides and adopts a G-quadruplex structure [ 166 ].…”

“…These findings suggest a superior efficacy of Apt/Tf-Dn/LUT compared with the two free drugs, whether combined with the aptamer or Tf individually, underscoring the synergistic effect of the drugs and dual targeting. Furthermore, Apt/Tf-Dn/LUT exhibited enhanced tumor distribution compared with other formulations [ 149 ].…”

Aptamers Versus Vascular Endothelial Growth Factor (VEGF): A New Battle against Ovarian Cancer

“…As a result of the two medications working synergistically, AP/Tf-Drn/Lut NPs demonstrated more inhibition to the tumor cells. The most potent anti-leukemic activity and lack of in vivo toxicity were presented by AP/Tf-Drn/Lut NPs [ 91 ].…”

“… ( A ) Classification of aptamers, ( B ) schematic illustration of the SELEX technique, and ( C ) aptamers in ovarian cancer diagnosis and treatment [ 18 , 51 , 91 ]. …”