Targeted delivery of doxorubicin by nano-loaded mesenchymal stem cells for lung melanoma metastases therapy

Yuekui Zhao,Jiamin Guo,Zhaocong Yang,Yumeng Shen,Murad Alahdal,Shunxiu Cao,Li Zong,Minjie Sun,Liang Jin,Ran Mo,Fangfang Zhang,Shanshan Tang

doi:10.1038/srep44758

Abstract

Poor antigenic presentation of tumor tissues and a lack of specific targets currently limit the success of nanoparticle delivery system. Cellular carrier technique has been recently explored extensively as a substitutive or supplement for traditional targeting delivery system. Here, we demonstrate the usage of mesenchymal stem cells (MSCs) loaded with doxorubicin containing polymer nanoparticles in pulmonary melanoma metastases therapy, as a modified technique of targeted delivery system. The characterizations of prepared nanoparticles and MSCs sensitivity to DOX and PLGA-DOX were measured. In vitro tumor tropism, and in vivo distributions of nanoparticles loaded MSCs were also investigated. The findings have demonstrated that, the modified system not only integrates the controlled-release property of nanoparticles but also exhibits tumor tropism and penetrative characteristics of MSCs. Furthermore, the in vitro and in vivo anti-tumor study has demonstrated that drug loaded MSCs had potent efficacy in lung melanoma metastases treatment.

Highlights

Bone marrow-derived MSCs were transfected with adenovirus vector to express CX3CL1 and inhibit the development of B16F10 lung metastases, the number of metastatic nodules treated with MSCs-CX3CL1 was significantly reduced by 84% compared with PBS group[27]
We reported for the first time, the application of mice adipose-derived MSCs were loaded with doxorubicin-containing PLGA nanoparticles (PLGA-DOX) for the treatment of pulmonary B16F10 melanoma metastases
MSCs isolated from adipose tissue in C57BL6 mice were loaded with PLGA-DOX nanoparticles to treat pulmonary metastases

Summary

Introduction

MSCs engineered with chemotherapeutics have been widely established for their tumor tropic delivery. MSCs overexpression of drug efflux pumps often hampers intracellular accumulation of small molecule therapeutics[19]. We supposed that, doxorubicin (DOX) containing nanoparticles that were formulated with poly (d, l-lactic-co-glycolic acid) (PLGA) will achieve successful drug retention in MSCs. MSCs derived from C57BL6 mice adipose tissue and loaded with PLGA-DOX nanoparticles (NP-MSCs) could target lung metastases in C57BL6 mice, suggesting a more effective methodology to treat lung metastases tumor (Fig. 1)

Methods

Results

Discussion

Conclusion