TY - JOUR
T1 - Cholesterol Metabolism Regulated Nanoliposome Ameliorates Chemo/Photothermal Therapy Reversing CD8+ T Cell Exhaustion
AU - Xue, Panpan
AU - Bai, Tingjie
AU - Zhuang, Huilan
AU - All, Angelo H.
AU - Yan, Shuangqian
AU - Zeng, Xuemei
N1 - Funding information:
The authors acknowledge the support from the National Natural Science Foundation of China (62275048, 82573561, and 32201153), the Science and Technology Planning Project of Fujian Province (2025J01668, 2023J01292, and 2021J05031), and the Cultivation Plan for Science and Technology Innovation Team from the College of Life Sciences, Fujian Normal University.
Publisher Copyright:
© 2025 The Author(s). Exploration published by Henan University and John Wiley & Sons Australia, Ltd.
PY - 2025/12/7
Y1 - 2025/12/7
N2 - Stimulating the immunogenic cell death (ICD) by chemical and photothermal agents triggers antitumor immune responses to tumor treatments. However, the abnormal cholesterol accumulation in cancer cells promotes tumor survival and metastasis, while the high concentration of cholesterol in the tumor microenvironment will result in T exhaustion. Herein, a cholesterol-regulable nanoliposome (ictLipo) that encapsulated with IR806, tirapazamine, and cholesterol oxidase (ChOx) was fabricated to boost chemo/photothermal-activated ICD and antitumor immune responses. Specifically, the released ChOx oxidizes cholesterol, accompanied by oxygen consumption and ATP reduction. Whereupon, tumoral anabatic hypoxia activates the toxicity of tirapazamine while ATP reduction strengthens photothermal therapy of the IR806 by suppression of HSP70. We found that this interactive strategy evokes robust ICD and reverses T-cell exhaustion. When combined with the immune checkpoint blockade, ictLipo can efficiently restrain breast cancer metastasis in two tumor models. The interactive strategy sheds new light on the immunological facet of cholesterol metabolism and may provide a new therapeutic strategy against breast cancer.
AB - Stimulating the immunogenic cell death (ICD) by chemical and photothermal agents triggers antitumor immune responses to tumor treatments. However, the abnormal cholesterol accumulation in cancer cells promotes tumor survival and metastasis, while the high concentration of cholesterol in the tumor microenvironment will result in T exhaustion. Herein, a cholesterol-regulable nanoliposome (ictLipo) that encapsulated with IR806, tirapazamine, and cholesterol oxidase (ChOx) was fabricated to boost chemo/photothermal-activated ICD and antitumor immune responses. Specifically, the released ChOx oxidizes cholesterol, accompanied by oxygen consumption and ATP reduction. Whereupon, tumoral anabatic hypoxia activates the toxicity of tirapazamine while ATP reduction strengthens photothermal therapy of the IR806 by suppression of HSP70. We found that this interactive strategy evokes robust ICD and reverses T-cell exhaustion. When combined with the immune checkpoint blockade, ictLipo can efficiently restrain breast cancer metastasis in two tumor models. The interactive strategy sheds new light on the immunological facet of cholesterol metabolism and may provide a new therapeutic strategy against breast cancer.
KW - checkpoint blockade
KW - cholesterol metabolism
KW - photothermal therapy
KW - T cell exhaustion
UR - https://www.scopus.com/pages/publications/105024115751
U2 - 10.1002/EXP.20240123
DO - 10.1002/EXP.20240123
M3 - Journal article
AN - SCOPUS:105024115751
SN - 2766-8509
JO - Exploration
JF - Exploration
M1 - 20240123
ER -
