TY - JOUR
T1 - Tailoring Aggregation Extent of Photosensitizers to Boost Phototherapy Potency for Eliciting Systemic Antitumor Immunity
AU - Zhao, Hao
AU - Xu, Jiabao
AU - Feng, Chan
AU - Ren, Jiayu
AU - Bao, Lin
AU - Zhao, Yanbing
AU - Tao, Wei
AU - Zhao, Yuliang
AU - Yang, Xiangliang
N1 - Funding Information:
This work was supported by the National Basic Research Program of China (Grant Nos. 2020YFA0710700, 2018YFA0208900 to X.L.Y.) and the National Natural Science Foundation of China (Grant Nos. 82172758 to Y.B.Z., and 81773653 to X.L.Y.). The authors thank Dingwen Shi, Chengyuan Sun, Le Jia, Xuan Tan, Qingqing Zhang, Yuxuan Xiong, Qiang Wang, Yiqian Wang, Jitang Chen, Ningbing Ye, Zelong Zhang, and Yuanyuan Ren from HUST for their help in animal experiments. The authors also thank the Analytical and Testing Center of HUST and the Research Core Facilities for Life Science (HUST) for the related analysis.
Funding Information:
This work was supported by the National Basic Research Program of China (Grant Nos. 2020YFA0710700, 2018YFA0208900 to X.L.Y.) and the National Natural Science Foundation of China (Grant Nos. 82172758 to Y.B.Z., and 81773653 to X.L.Y.). The authors thank Dingwen Shi, Chengyuan Sun, Le Jia, Xuan Tan, Qingqing Zhang, Yuxuan Xiong, Qiang Wang, Yiqian Wang, Jitang Chen, Ningbing Ye, Zelong Zhang, and Yuanyuan Ren from HUST for their help in animal experiments. The authors also thank the Analytical and Testing Center of HUST and the Research Core Facilities for Life Science (HUST) for the related analysis.
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022/2/24
Y1 - 2022/2/24
N2 - Phototherapy is effective for triggering the immunogenic cell death (ICD) effect. However, its efficacy is limited by low 1O2 generation and photothermal conversion efficacy due to two irreconcilable obstacles, namely the aggregation-caused-quenching (ACQ) effect and photobleaching. In this work, a discretely integrated nanofabrication (DIN) platform (Pt-ICG/PES) is developed by facile coordination coassembly of cisplatin (Pt), photosensitizer molecules (indocyanine green (ICG)), and polymeric spacer (p(MEO2MA-co-OEGMA)-b-pSS (PES)). By controlling the ICG/PES feeding ratio, the aggregation of ICG can be easily tailored using PES as an isolator to balance the ACQ effect and photobleaching, thereby maximizing the phototherapy potency of Pt-ICG/PES. With the optimized ratio of each component, Pt-ICG/PES integrates the complementarity of photodynamic therapy, photothermal therapy, and chemotherapeutics to magnify the ICD effect, exerting a synergistic antitumor immunity-promoting effect. Additionally, temperature-sensitive PES enables photothermally guided drug delivery. In a tumor-bearing mouse model, Pt-ICG/PES elicits effective release of danger-associated molecular patterns, dendritic cell maturation, cytotoxic T lymphocytes activation, cytokine secretion, M2 macrophage repolarization, and distal tumor suppression, confirming the excellent in situ tumor ICD effect as well as robust systematic antitumor immunity. Ultimately, a versatile DIN strategy is developed to optimize the phototherapeutic efficacy for improving antitumor effects and strengthening systemic antitumor immunity.
AB - Phototherapy is effective for triggering the immunogenic cell death (ICD) effect. However, its efficacy is limited by low 1O2 generation and photothermal conversion efficacy due to two irreconcilable obstacles, namely the aggregation-caused-quenching (ACQ) effect and photobleaching. In this work, a discretely integrated nanofabrication (DIN) platform (Pt-ICG/PES) is developed by facile coordination coassembly of cisplatin (Pt), photosensitizer molecules (indocyanine green (ICG)), and polymeric spacer (p(MEO2MA-co-OEGMA)-b-pSS (PES)). By controlling the ICG/PES feeding ratio, the aggregation of ICG can be easily tailored using PES as an isolator to balance the ACQ effect and photobleaching, thereby maximizing the phototherapy potency of Pt-ICG/PES. With the optimized ratio of each component, Pt-ICG/PES integrates the complementarity of photodynamic therapy, photothermal therapy, and chemotherapeutics to magnify the ICD effect, exerting a synergistic antitumor immunity-promoting effect. Additionally, temperature-sensitive PES enables photothermally guided drug delivery. In a tumor-bearing mouse model, Pt-ICG/PES elicits effective release of danger-associated molecular patterns, dendritic cell maturation, cytotoxic T lymphocytes activation, cytokine secretion, M2 macrophage repolarization, and distal tumor suppression, confirming the excellent in situ tumor ICD effect as well as robust systematic antitumor immunity. Ultimately, a versatile DIN strategy is developed to optimize the phototherapeutic efficacy for improving antitumor effects and strengthening systemic antitumor immunity.
KW - antitumor immunity
KW - chemotherapy
KW - discrete integration
KW - immunogenic cell death
KW - phototherapy
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U2 - 10.1002/adma.202106390
DO - 10.1002/adma.202106390
M3 - Article
C2 - 34783098
AN - SCOPUS:85122754892
SN - 0935-9648
VL - 34
JO - Advanced Materials
JF - Advanced Materials
IS - 8
M1 - 2106390
ER -