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. 2023 Jan 6:17:1-13.
doi: 10.2147/DDDT.S387246. eCollection 2023.

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

Yuanyuan Zhu  1 , Wei Zhang  1 , Jing Chen  1
Affiliations

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

Yuanyuan Zhu et al. Drug Des Devel Ther. .

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.

Keywords: acute myeloid leukemia; aptamer; daunorubicin; luteolin; nanodrug-delivery system; transferrin.

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Conflict of interest statement

The authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Scheme (A) and TEM images (B) of AP/Tf-Drn/Lut NPs.
Figure 2
Figure 2
Changes in particle size (A) and EE (B) analyzed in PBS and culture medium (FBS). In vitro drug-release behavior of Drn (C) or Lut (D) from nanosystems evaluated by dialysis.
Figure 3
Figure 3
Cytotoxicity of AP/Tf-Drn/Lut NPs and other formulations evaluated with MTS assays.
Figure 4
Figure 4
In vivo AML therapy efficiency: Tumor size (A) and body weight (B).
Figure 5
Figure 5
In vivo Drn (A and C) and Lut (B and D) distribution in tissue after 1 h (A and B) and 48 h (C and D) of drug administration. *P<0.05.
See this image and copyright information in PMC

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