Co-delivery of Tim-3 mAb and sorafenib enhanced chemoimmunotherapy for hepatocellular carcinoma using "responsive shell-peeling" mesoporous silica nanoparticles / 药学学报

Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively. In vivo tumor inhibition study results demonstrated that ST-MSNs can significantly enhance synergistic antitumor activity compared with sequential administration of free SF solution and Tim-3 mAb solution. Meanwhile, the expression of antitumor cytokines IFN-γ, IL-12 and the percentage of CD3+CD4+ cells, CD3+CD8+ cells in tumors were upregulated after the administration of ST-MSNs, demonstrating good immunomodulatory ability. In addition, within the dosage range, the ST-MSNs had low cytotoxicity and hemolysis, and no obvious tissue toxicity was observed. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Shandong University. In conclusion, this study provided a promising drug combination of chemoimmunotherapy with good application prospects for clinical HCC treatment, and exhibited a potential drug carrier for clinical chemoimmunotherapy.

Research progress in stimuli responsive mesoporous silica nanoparticles for cancer diagnosis and therapy / 中国药学杂志

Referring to the recent literatures, this review summarized the recent research progress of SR-MSNDDS which were responsive to different stimulus, including pH, reduction, temperature, light, magnetic field or biomolecules, etc. To review the recent research progress of stimuli responsive mesoporous silica nanoparticle (SR-MSNDDS) drug delivery systems and predict their application prospect. SR-MSNDDS could overcome the problem of controlling drug release from MSN and achieve tumor specific drug release, which has become a research hotspot in the field of tumor diagnosis and therapy.