A nanoselenium-coating biomimetic cytomembrane nanoplatform for mitochondrial targeted chemotherapy- and chemodynamic therapy through manganese and doxorubicin codelivery

Jianmin Xiao,Miao Yan,Geng Tian,Ke Zhou,Junchao Qian,Yuehao Gan,Biao Hong,Zhengyan Wu,Hui Chen,Zhaowei Xu,Guilong Zhang

doi:10.1186/s12951-021-00971-9

Abstract

The cell membrane is widely considered as a promising delivery nanocarrier due to its excellent properties. In this study, self-assembled Pseudomonas geniculate cell membranes were prepared with high yield as drug nanocarriers, and named BMMPs. BMMPs showed excellent biosafety, and could be more efficiently internalized by cancer cells than traditional red cell membrane nanocarriers, indicating that BMMPs could deliver more drug into cancer cells. Subsequently, the BMMPs were coated with nanoselenium (Se), and subsequently loaded with Mn2+ ions and doxorubicin (DOX) to fabricate a functional nanoplatform (BMMP-Mn2+/Se/DOX). Notably, in this nanoplatform, Se nanoparticles activated superoxide dismutase-1 (SOD-1) expression and subsequently up-regulated downstream H2O2 levels. Next, the released Mn2+ ions catalyzed H2O2 to highly toxic hydroxyl radicals (·OH), inducing mitochondrial damage. In addition, the BMMP-Mn2+/Se nanoplatform inhibited glutathione peroxidase 4 (GPX4) expression and further accelerated intracellular reactive oxygen species (ROS) generation. Notably, the BMMP-Mn2+/Se/DOX nanoplatform exhibited increased effectiveness in inducing cancer cell death through mitochondrial and nuclear targeting dual-mode therapeutic pathways and showed negligible toxicity to normal organs. Therefore, this nanoplatform may represent a promising drug delivery system for achieving a safe, effective, and accurate cancer therapeutic plan.

Highlights

Drug delivery systems (DDSs) are actively exploited to enhance the delivery efficiency of drugs and decrease their systemic side effects [1–6]
Hydrodynamic size results indicated that BMMP-Mn2+/Se was larger than BMMP-Mn2+, which might be attributed to the aggregation and vesicle fusion of nanoparticles (Fig. 1f )
The above results demonstrated that BMMP-Mn2+/Se nanoplatform had excellent stability in these media

Summary

Introduction

Drug delivery systems (DDSs) are actively exploited to enhance the delivery efficiency of drugs and decrease their systemic side effects [1–6]. The biosafety and simple fabrication of DDSs are critical factors for promoting their wide application in the biomedical field [7–9]. An increasing number of studies reported that some DDSs including metal-, silica-, carbon-, or polymer-based nanocarriers exhibited potential side effects [10–18], which significantly limited their clinical use. Biomimetic nanomaterials (BMNs) have attracted extensive attention in worldwide and exhibit great application potential for DDSs due to their excellent biocompatibility, long blood circulation time, and internalization efficiency [19–22]. Along with the wide application of the cell membrane in DDSs, some limitations have been gradually exposed, such as the complexity of preparation technology, uncontrollable morphology, and poor colloid stability, which seriously limit cell membrane-based DDSs in clinical use. It is highly important to develop methods for the preparation of biomimetic cell membranes in a simple and high-yield manner

Methods

Results

Conclusion