Self-assembled targeted nanoparticles based on transferrin-modified eight-arm-polyethylene glycol-dihydroartemisinin conjugate.

Kefeng Liu,Jiandu Lei,Chunxiao Li,Luying Wang,Jing Liu,Lin Dai

doi:10.1038/srep29461

Abstract

Poor delivery of insoluble anticancer drugs has so far precluded their clinical application. In this study, an efficient tumor targeted-nanoparticle delivery system, transferrin-eight-arm-polyethylene glycol–dihydroartemisinin nanoparticles (TF-8arm-PEG-DHA NPs) for the vehiculation of dihydroartemisinin (DHA) was first prepared and evaluated for its targeting efficiency and cytotoxicity in vitro and in vivo to Lewis lung carcinoma (LLC) cells, which overexpress transferrin receptors (TFRs). The synthesized TF-8arm-PEG–DHA NPs had high solubility (~102 fold of free DHA), relatively high drug loading (~10 wt% DHA), long circulating half-life and moderate particle size (~147 nm). The in vitro cytotoxicity and in vivo tumor growth inhibition studies in LLC-tumor bearing mice confirmed the enhanced efficacy of TF-modified 8arm-PEG-DHA NPs compared to free DHA and non-modified 8arm-PEG-DHA NPs. All these results together supported that the formulation developed in this work exhibited great potential as an effective tumor targeting delivery system for insoluble anticancer drugs.

Highlights

Show that the PEG with a comparatively low molecular weight may face the risk of being fast removed by kidney owe to its small size[18,19]
Transferrin (TF, MW 80 kDa) is a serum glycoprotein that helps to transport iron required as a cofactor for DNA synthesis into rapidly growing cells via the transferrin receptor (TFR)[31]
This leads to an increased expression of TFR on the surface of cancer cells that can be exploited for the purpose of active targeting of nanocarriers to these cells

Summary

Introduction

Show that the PEG with a comparatively low molecular weight may face the risk of being fast removed by kidney owe to its small size[18,19]. Because of the rapid rate of proliferation of cancer cells, their demand for iron is much greater than normal cells This leads to an increased expression of TFR on the surface of cancer cells that can be exploited for the purpose of active targeting of nanocarriers to these cells. Transferrin (TF), the targeting ligand, was conjugated to the side chain of 8arm-PEG-DHA NPs for target ability. This targeting delivery system can provide lower systemic toxicity and higher therapeutics efficiency. This paper reports the design, synthesis, in vitro and in vivo evaluation of TF-8arm-PEG-DHA NPs with TF as the targeting ligand to enhance the cellular uptake and anti-cancer activity through receptor-mediated endocytosis between TF and TFR

Methods

Results

Conclusion