A synergistic approach for modulating the tumor microenvironment to enhance nano-immunotherapy in sarcomas

• DOI: 10.1016/j.neo.2024.100990
• Publication Date: 2024-03-22T10:27:50Z
• Authors: Fotios Mpekris; Myrofora Panagi; Antonia Charalambous; Chrysovalantis Vo...; Christina Michael; Antonia Papoui; Triantafyllos Sty...
• Keywords: 0301 basic medicine; 03 medical and health sciences; Nanomedicine; Mechanotherapeutics; Ultrasound; Sonopermeation; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Immune checkpoint inhibition; RC254-282; Original Research

The lack of properly perfused blood vessels within tumors can significantly hinder the distribution drugs, leading to reduced treatment effectiveness and having a negative impact on quality life patients with cancer. This problem is particularly pronounced in desmoplastic cancers, where interactions between cancer cells, stromal fibrotic matrix lead tumor stiffness compression most tumor. To address this issue, two mechanotherapy approaches-mechanotherapeutics ultrasound sonopermeation-have been employed separately treat vascular abnormalities have reached clinical trials. Here, we performed vivo studies sarcomas, explore conditions under which these strategies could be optimally combined enhance perfusion efficacy nano-immunotherapy. Our findings demonstrate that combination anti-histamine drug ketotifen, as mechanotherapeutic, sonopermeation effectively alleviates mechanical forces by decreasing 50 % collagen hyaluronan levels thus, reshaping microenvironment. Furthermore, therapy normalizes vasculature increasing two-fold pericytes coverage. not only improves six times but also enhances delivery. As result, vessel functionality enhanced, increased infiltration 40 immune cells (CD4