A Natural Bacterium-Produced Membrane-Bound Nanocarrier for Drug Combination Therapy.

Ruimin Long,Qiongjia Deng,Shibin Wang,Qinglei Dai,Yuangang Liu,Xia Zhou

doi:10.3390/ma9110889

Abstract

To minimize the non-specific toxicity of drug combination during cancer therapy, we prepared a new system synthesized from bacteria to deliver the anticancer drugs cytosine arabinoside (Ara-C) and daunorubicin (DNR). In this study, we selected genipin (GP) and poly-l-glutamic acid (PLGA) as dual crosslinkers. Herewith, we demonstrated the preparation, characterization and in vitro antitumor effects of Ara-C and DNR loaded GP-PLGA-modified bacterial magnetosomes (BMs) (ADBMs-P). The results show that this new system is stable and exhibits optimal drug-loading properties. The average diameters of BMs and ADBMs-P were 42.0 ± 8.6 nm and 65.5 ± 8.9 nm, respectively, and the zeta potential of ADBMs-P (−42.0 ± 6.4 mV) was significantly less than that of BMs (−28.6 ± 7.6 mV). The optimal encapsulation efficiency and drug loading of Ara-C were 68.4% ± 9.4% and 32.4% ± 2.9%, respectively, and those of DNR were 36.1% ± 2.5% and 17.9% ± 1.6%. Interestingly, this system also exhibits long-term release behaviour sequentially, without an initial burst release. The Ara-C drug continued to release about 85% within 40 days, while DNR release lasted only for 13 days. Moreover, similar to free drugs, ADBMs-Ps are strongly cytotoxic to cancer cells in vitro (HL-60 cells), with the inhibition rate approximately 96%. This study reveals that this new system has a potential for drug delivery application in the future, especially for combination therapy.

Highlights

Cancer is one of the most common causes of death in humans
We have reported that bacterial magnetosomes (BMs) can be successfully coupled to cytosine arabinoside (Ara-C) through the surface modification of BMs by poly-L-glutamic acid (PLGA) [17]
We developed a drug delivery system by the utilization of a natural dual functional crosslinker GP, which has the advantages of biocompatibility, low toxicity, and some pharmaceutical properties and will broaden the application of BMs

Summary

Introduction

Cancer is one of the most common causes of death in humans. The preferred clinical treatments for cancer include radiotherapy and chemotherapy. Combination drug therapy is administering two or more drugs that provide improved therapeutic efficacy than a single drug, and has become an expedient method of chemotherapy aimed at treating various types of cancers. Direct drug combination can often exert additional side effects due to their exposure to normal cells. The use of drug carriers can address this issue, as these compounds can eliminate the side effects associated with it and delivers drugs in a sustained fashion. Several drug carriers, including liposomes [1], polymer nanoparticles [2] and lipid nanoparticles [3]

Methods

Results

Conclusion