“Three‐in‐one”: A Photoactivable Nanoplatform Evokes Anti‐Immune Response by Inhibiting BRD4‐cMYC‐PDL1 Axis to Intensify Photo‐Immunotherapy

• DOI: 10.1002/adhm.202304093
• Publication Date: 2024-02-27T05:29:49Z
• Authors: Ayeskanta Mohanty; Mingyu Lee; Adityanarayan Moh...; Hwangjae Lee; Arathy Vasukutty; Seonguk Baek; Jae Young Lee; In‐Kyu Park
• Keywords: Immune checkpoint; Cancer Immunotherapy; Immunogenic cell death

Abstract Combinatorial immuno‐cancer therapy is recognized as a promising approach for efficiently treating malignant tumors. Yet, the development of multifunctional nanomedicine capable precise tumor targeting, remote activation, and immune‐regulating drug delivery remains significant challenge. In this study, nanoparticles loaded with an immune checkpoint inhibitor (JQ‐1) using polypyrrole/hyaluronic acid (PPyHA/JQ‐1) are developed. These offer active photothermal ablation near‐infrared light, laser‐controlled JQ‐1 release efficient breast cancer treatment. When molecular weight HA varies (from 6.8 kDa to 3 MDa) in PPyHA nanoparticles, it found that synthesized 1 MDa HA, referred (1 m ), show most suitable properties, including small hydrodynamic size, high surface contents, colloidal stability. Upon 808 nm laser irradiation, PPyHA/JQ‐1 elevates temperature above 55 °C, which sufficient thermal microenvironment (TME). Notably, controlled substantially inhibits expression cancer‐promoting genes. Furthermore, effectively suppresses programmed cell death ligand (PD‐L1) prolongs dendritic maturation CD8+ T activation against both vitro vivo. treatment simultaneously provides regression through blockade, leading durable antitumor‐immune response. Overall, “Three‐in‐one” immunotherapeutic photo‐activable have potential be beneficial targeted combinatorial TNBC.