Objective: Osteoarthritis (OA) is a common subtype of arthritis. To date, treatment of OA focuses primarily on alleviating pain and improving joint function. The lack of a vascular system within synovial joints and the rapid removal of agents due to synovial exchange hinder continuous delivery of OA drugs. However, these obstacles are being addressed by promising nanoscale drugs.Methods: We synthesize and assemble a hydrogen peroxide [H2O2, belongs to the category of active oxygen species (ROS)]-sensitive nanomicelle, which is loaded with the anti-inflammation drug dexamethasone and chondrogenic differentiation factor cartilage-derivedmor-phogeneticprotein-1. The micelle can induce bone marrow mesenchymal stem cells to repair cartilage while inhibiting joint inflammation.Results: The prepared nanoparticles were of uniform size and displayed an obvious core-shell structure. Under H2O2 stimulation, the shell layer could be removed gradually. The drug-loaded micelle effectively inhibited proliferation of activated macrophages, induced macrophage apoptosis with an anti-inflammatory effect, and caused the BMSCs to differentiate into chondrocytes.Conclusion: This work provides an experimental and theoretical basis for further development of a drug-loaded micelle in the healing of osteoarthritis.
Circumventing immune resistance and boosting immune response is the ultimate goal of cancer immunotherapy . Herein, we reported a tumor-associated macrophage (TAM) membrane-camouflaged nanodecoy containing a self-amplifying reactive oxygen species (ROS)-sensitive prodrug nanoparticle for specifically inducing immunogenic cell death (ICD) in combination with TAM depletion. A versatile ROS-cleavable camptothecin (CPT) prodrug (DCC) was synthesized through a thioacetal linker between CPT and the ROS generator cinnamaldehyde (CA), which could self-assemble into a uniform prodrug nanoparticle to realize a positive feedback loop of “ROS-triggered CA/CPT release and CA/CPT-mediated ROS generation.” This DCC was further modified with the TAM membrane (abbreviated as DCC@M2), which could not only target both primary tumors and lung metastasis nodules through VCAM-1/α 4 β 1 integrin interaction but also absorb CSF-1 secreted by tumor cells to disturb the interaction between TAMs and cancer cells. Our nanodecoy could effectively induce ICD cascade and deplete TAMs for priming tumor-specific effector T cell infiltration for antitumor immune response activation, which represents a versatile approach for cancer immunotherapy. Statement of significance A tumor-associated macrophage (TAM) membrane-camouflaged nanodecoy containing a self-amplifying reactive oxygen species (ROS)-sensitive prodrug nanoparticle was fabricated for the first time. This ROS-cleavable camptothecin (CPT)/cinnamaldehyde (CA) prodrug (DCC) could self-assemble into a uniform nanoparticle to realize the positive feedback loop of “ROS-triggered CA/CPT release and CA/CPT-mediated ROS generation.” After TAM membrane coating, this system (DCC@M2) could not only target both primary tumors and lung metastatic nodules but also scavenge CSF-1 secreted by tumor cells for TAM depletion for sufficient chemotherapy-sensitized immunotherapy.
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