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. 2023 Jun 16;14:3593. doi: 10.1038/s41467-023-39035-x

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a The chemical structure of the nanovesicles integrating a phospholipid prodrug of JQ1, photosensitizer pyropheophorbide a (PPa), and transforming growth factor β receptor 1 (TGFR1) inhibitor LY2157299 (LY). b Schematic illustration of the cascade drug release of the nanovesicles. Matrix metallopeptidase-2 (MMP-2) cleaved the poly(ethylene glycol) (PEG) corona and induced the LY release. PPa generated singlet oxygen upon near-infrared (NIR) laser irradiation to release JQ1-SH. c Diagram illustrating the mechanism of the nanovesicles to overcome immune resistance. The nanovesicles (ELJNV) breach the physical barrier and enhance the tumor-specific immune response upon the 671 nm laser irradiation to overcome the intrinsic immune resistance and simultaneously suppress the interferon-γ (IFN-γ)-induced inducible immune resistance in vivo. FI fluorescence imaging, PAI photoacoustic imaging, MRI nuclear magnetic resonance imaging, ROS reactive oxygen species, ECM extracellular matrix, CTLs cytotoxic T lymphocytes, α-SMA α-smooth muscle actin, PDT photodynamic therapy, ICD immunogenic cell death, PD-L1 programmed cell death 1, BRD4 bromodomain-containing protein 4, HMGB1 high mobility group box protein 1, CRT calreticulin, DC dendritic cell, CAFs cancer-associated fibroblasts, DPPC 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, JTP JQ1-thioketal (TK)-pPC, TGF-β1 transforming growth factor β1, ¹O₂ singlet oxygen, Gd³⁺ gadolinium ion.