A natural bacterium-produced membrane-bound nanocarrier for drug combination therapy

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.