Journal
CHEMICAL ENGINEERING JOURNAL
Volume 450, Issue -, Pages -Publisher
ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2022.138210
Keywords
Mitochondrial targeting; Sonosensitizer; Sonodynamic therapy; Immunotherapy
Categories
Funding
- National Natural Science Foundation of China [21771065]
- Natural Science Foundation of Guangdong [2019A1515012021]
- Science and Technology Program of Guangzhou [2019050001]
- Major Program of Ningbo Science and Technology Innovation 2025, Zhejiang Province, China [2020Z093]
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In this study, a new sonosensitizer GdPorP was designed, which could efficiently produce ROS upon ultrasound irradiation and specifically accumulate in mitochondria. By combining the delivery of GdPorP with a pH-sensitive nanomedicine and an IDO inhibitor, the study successfully established a GdPorP-approved sonodynamic-immunotherapy (SDIT) that can specifically map and suppress liver tumors while enhancing systemic antitumor immune response.
Conventional sonodynamic therapy (SDT) is still limited in conquering localized tumors owing to its low reactive oxygen species (ROS)-based therapeutic effect and undesirably inhibiting effect of immunosuppressive tumor microenvironment (ITM). In this study, we reasonably designed a new sonosensitizer, gadolinium (III) por-phyrinate (GdPorP), which could efficiently produce ROS upon ultrasound irradiation and specifically accu-mulate in mitochondria. The GdPorP-based mitochondria-specific sonodamage could induce high-efficiency cell apoptosis and cascade to producing large-scale immunogenic cell death. After GdPorP systematically delivered together with the indoleamine 2,3-dioxygenase (IDO) inhibitor by a pH-sensitive nanomedicine, the localized liver tumor was specifically mapped by the switching-on MRI. And the nanomedicine could not only efficiently suppress the progression of primary liver tumors but also simultaneously boost the systematic antitumor immune effect via the inhibition of ITM. The GdPorP-approved sonodynamic-immunotherapy (SDIT) has thereby been established as a new paradigm for upgrading the efficacy of cancer SDT.
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