IL-1 Family Members in Bone Sarcomas.

IL-1 family members have multiple pleiotropic functions affecting various tissues and cells, including the regulation of the immune response, hematopoietic homeostasis, bone remodeling, neuronal physiology, and synaptic plasticity. Many of these activities are involved in various pathological processes and immunological disorders, including tumor initiation and progression. Indeed, IL-1 family members have been described to contribute to shaping the tumor microenvironment (TME), determining immune evasion and drug resistance, and to sustain tumor aggressiveness and metastasis. This review addresses the role of IL-1 family members in bone sarcomas, particularly the highly metastatic osteosarcoma (OS) and Ewing sarcoma (EWS), and discusses the IL-1-family-related mechanisms that play a role in bone metastasis development. We also consider the therapeutic implications of targeting IL-1 family members, which have been proposed as (i) relevant targets for anti-tumor and anti-metastatic drugs; (ii) immune checkpoints for immune suppression; and (iii) potential antigens for immunotherapy.

Programmable Release of Chemotherapeutics from Ferrocene-Based Injectable Hydrogels Slows Melanoma Growth.

Hydrogel-based injectable drug delivery systems provide temporally and spatially controlled drug release with reduced adverse effects on healthy tissues. Therefore, they represent a promising therapeutic option for unresectable solid tumor entities. In this study, a peptide-starPEG/hyaluronic acid-based physical hydrogel is modified with ferrocene to provide a programmable drug release orchestrated by matrix-drug interaction and local reactive oxygen species (ROS). The injectable ROS-responsive hydrogel (hiROSponse) exhibits adequate biocompatibility and biodegradability, which are important for clinical applications. HiROSponse is loaded with the two cytostatic drugs (hiROSponsedox/ptx) doxorubicin (dox) and paclitaxel (ptx). Dox is a hydrophilic compound and its release is mainly controlled by Fickian diffusion, while the hydrophobic interactions between ptx and ferrocene can control its release and thus be regulated by the oxidation of ferrocene to the more hydrophilic state of ferrocenium. In a syngeneic malignant melanoma-bearing mouse model, hiROSponsedox/ptx slows tumor growth without causing adverse side effects and doubles the relative survival probability. Programmable release is further demonstrated in a tumor model with a low physiological ROS level, where dox release, low dose local irradiation, and the resulting ROS-triggered ptx release lead to tumor growth inhibition and increased survival.