INTRODUCTION: Mesoporous bioactive glass nanoparticles (MBG NPs) have received a significant amount of interest for their potential to treat cancer cells with high drug loading capacity and excellent stability, providing a controlled drug release platform into the malignant tumor . Although enhanced permeability and retention (EPR) effects allow MBG NPs to accumulate at tumor sites, the inferior tumor targeting and ineffective immune escape performance of MBG NPs remain significant challenges. Herein, the tumor targeting and immune escape properties of MBG NPs that were camouflaged with tumor-derived cell membrane and macrophage-derived cell membrane were initially evaluated in vitro and in vivo. And the macrophage cell membrane bionic modified MBG NPs embedding glucose oxidase (QO) drug delivery system (RAW@MBG@QO DDS) was constructed based on its superior performance in immune escape. Finally, we systematically investigated the tumor treatment effect and biosafety of RAW@MBG@QO DDS in order to expand the clinical application of MBG NPs as a drug delivery.
METHODS: MBG NPs were synthesized by a sol-gel method combined with a hydrothermal reaction. For cell membrane camouflage, 4T1 cells and RAW 264.7 cells were separately suspended in a hypotonic lysing buffer and then disrupted using a Dounce homogenizer. The homogenized solution was secondary centrifuged. The two kinds of membranes were collected and mixed with MBG NPs under the sonication induced assembly, respectively. The tumor target and immune escape performance of both cytomembrane coated MBG NPs were analyzed using the in-vitro cell model and the in-situ tumor model, and the RAW 264.7 cells were filtered for developing RAW@MBG@QO DDS. The cytotoxicity, oxidative stress, and tumor suppressive effects mediated by RAW@MBG@QO DDS were further investigated.
RESULTS & DISCUSSION: In the present study, we have successfully constructed two kinds of cytomembrane coated MBG NPs, both of which showed significantly higher tumor targeting compared to MBG. MBG NPs coated with macrophage membrane were more effective at avoiding being phagocytosed and eliminated by the immune cells. Following that, our results indicated that RAW@MBG@QO DDS could release QOs in a controlled fashion to induce the oxidative stress and apoptosis on tumor cells using the catalytic reaction of glucose oxidase, and showed excellent tumor suppressive effect in vivo. Meanwhile, RAW@MBG@QO DDS had the advantage of QO-controlled release, which effectively mitigated blood homeostasis interference and avoided potential toxicological risks.
CONCLUSIONS: Our findings suggest that the cell membrane camouflage MBG NPs embedding glucose oxidase drug delivery system exhibits high efficiency for tumor suppression, which can promote the development of MBG NPs serving as as excellent drug delivery vehicles for cancer therapy.
ACKNOWLEDGEMENTS: This work was supported by grants from National Natural Science Foundation of China (31900956, 81971751) and Shanghai Sailing Program (19YF1427400).
 E. Sharifi, A. Bigham, S. Yousefiasl, M. Trovato, M. Ghomi, Y. Esmaeili, P. Samadi, A. Zarrabi, M. Ashrafizadeh, S.J.A.S. Sharifi, Mesoporous Bioactive Glasses in Cancer Diagnosis and Therapy: Stimuli‐Responsive, Toxicity, Immunogenicity, and Clinical Translation. Advanced Science, 2021: 2102678.