Construction of a Novel Magnetic Targeting Anti-Tumor Drug Delivery System: Cytosine Arabinoside-Loaded Bacterial Magnetosome.

Qiongjia Deng,Yuangang Liu,Wenguo Wu,Shenjian Wu,Maobin Xie,Aizheng Chen,Shibin Wang

doi:10.3390/ma6093755

Abstract

To ease the side effects triggered by cytosine arabinoside (Ara-C) for acute leukemia treatment, a novel magnetic targeting anti-tumor drug delivery system was constructed through bacterial magnetosomes (BMs) from Magnetospirillum magneticum AMB-1 combined with Ara-C by crosslinking of genipin (GP). The results showed that Ara-C could be bonded onto the membrane surface of BMs effectively through chemical crosslinking induced by dual hand reagents GP. The average diameters of BMs and Ara-C-coupled BMs (ABMs) were 42.0 ± 8.6 and 72.7 ± 6.0 nm respectively, and the zeta potentials (−38.1 ± 9.1) revealed that these systems were stable, confirming the stability of the system. The optimal encapsulation efficiency and drug loading were 89.05% ± 2.33% and 47.05% ± 0.64% respectively when crosslinking reaction lasted for 72 h. The system also presented long-term stability and release behaviors without initial burst release (Ara-C could be released 80% within three months). Our results indicate that BMs have great potential in biomedical and clinical fields as a novel anti-tumor drug carrier.

Highlights

Cytosine arabinoside (Ara-C) is a pyrimidine anti-metabolism of chemotherapeutic agent, which is most commonly used in the treatment of acute myelogenous leukemia [1]
(42.0 ± 8.6 nm), the average particle size of Ara-C-coupled BMs (ABMs) increased to 72.7 ± 6.0 nm, which suggested that
Our results clearly show that bacterial magnetosomes (BMs) isolated from M. magneticum AMB-1 can be used as a carrier of anticancer drugs with the help of proteins and other functional groups embedded in its membrane

Summary

Introduction

Cytosine arabinoside (Ara-C) is a pyrimidine anti-metabolism of chemotherapeutic agent, which is most commonly used in the treatment of acute myelogenous leukemia [1]. It can induce cell death of rapidly proliferating cells via blocking the synthesis of nucleic acids from inhibition of the DNA polymerase [2]. Since the cytotoxicity associates with the concentration and action time [6], the controlled release of a low dosage of Ara-C at the damage location will provide an efficient way to reduce its severe adverse effects and subsequently enhance the curative effect. The drug loading was relatively low and targeted therapy was not reflected, which would limit the further application of Ara-C

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Conclusion