Deep Penetration of Nanolevel Drugs and Micrometer-Level T Cells Promoted by Nanomotors for Cancer Immunochemotherapy.

The ability of nanomotors to promote the deep penetration of themselves and the loaded drugs in diseased tissues has been proposed and confirmed. However, whether such motion behavior of the nanomotors can also promote deep penetration of micrometer-sized immune cells in the diseased microenvironment, which is important for the immunotherapy of some diseases, has not been mentioned. Herein, we construct a nitric oxide (NO)-driven nanomotor that can move in the tumor microenvironment, focusing on its motion behavior and the role of NO, the beneficial product released during movement from this kind of nanomotor, in regulating the infiltration behavior and activity of immune cells. It can be found that the drug-loaded nanomotors with both NO-releasing ability and motility can promote the normalization of the tumor vasculature system and the degradation of the intrinsic extracellular matrix (ECM), which can significantly improve the tumor infiltration ability of T cells in vivo. The efficiency of T-cell infiltration in tumor tissue in vivo increased from 2.1 to 28.2%. Both subcutaneous and intraperitoneal implantation tumor models can validate the excellent antitumor effect of drug-loaded NO-driven nanomotors. This combination of motility of the power source from nanomotors and their physiological function offers a design idea for therapeutic agents for the future immunotherapy of many diseases.

Platelet-derived porous nanomotor for thrombus therapy.

The treatment difficulties of venous thrombosis include short half-life, low utilization, and poor penetration of drugs at thrombus site. Here, we develop one kind of mesoporous/macroporous silica/platinum nanomotors with platelet membrane (PM) modification (MMNM/PM) for sequentially targeting delivery of thrombolytic and anticoagulant drugs for thrombus treatment. Regulated by the special proteins on PM, the nanomotors target the thrombus site and then PM can be ruptured under near-infrared (NIR) irradiation to achieve desirable sequential drug release, including rapid release of thrombolytic urokinase (3 hours) and slow release of anticoagulant heparin (>20 days). Meantime, the motion ability of nanomotors under NIR irradiation can effectively promote them to penetrate deeply in thrombus site to enhance retention ratio. The in vitro and in vivo evaluation results confirm that the synergistic effect of targeting ability from PM and motion ability from nanomotors can notably enhance the thrombolysis effect in both static/dynamic thrombus and rat model.