Multifunctional Nanoplatform-Mediated Chemo-Photothermal Therapy Combines Immunogenic Cell Death with Checkpoint Blockade to Combat Triple-Negative Breast Cancer and Distant Metastasis

作者全名："Zhu, Hui; Yang, Ke; Yao, Huan; Chen, Xueying; Yan, Shujin; He, Yiman; Cao, Yang; Luo, Jie; Wang, Dong"

作者地址："[Zhu, Hui; Yao, Huan; Chen, Xueying; Yan, Shujin; He, Yiman; Luo, Jie; Wang, Dong] Chongqing Med Univ, Affiliated Hosp 1, Dept Ultrasound, Chongqing, Peoples R China; [Zhu, Hui; Yan, Shujin; He, Yiman; Cao, Yang] Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing, Peoples R China; [Yang, Ke] Chongqing Med Univ, Childrens Hosp, Pediat Res Inst, Chongqing, Peoples R China; [Luo, Jie; Wang, Dong] Chongqing Med Univ, Affiliated Hosp 1, Dept Ultrasound, 1 Youyi Rd, Chongqing 400042, Peoples R China"

通信作者："Luo, J; Wang, D (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Ultrasound, 1 Youyi Rd, Chongqing 400042, Peoples R China."

来源：INTERNATIONAL JOURNAL OF NANOMEDICINE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001008813400001

JCR分区：Q1

影响因子：6.6

年份：2023

卷号：18

期号：　

开始页：3109

结束页：3124

文献类型：Article

关键词：immunogenic cell death; immunotherapy; checkpoint blockade; chemo-photothermal therapy; triple-negative breast cancer

摘要："Background: Breast cancer has become the most common cancer in women. Compare with other subtypes of breast cancer, triple -negative breast cancer (TNBC) is more likely to relapse and metastasize. Highly effective therapeutic strategies are desperately needed to be explored. In this study, a multifunctional nanoplatform is expected to mediate chemo-photothermal therapy, which can combine immunogenic cell death with checkpoint blockade to combat TNBC and distant metastasis.Methods: Poly (lactic acid-glycolic acid)-Poly (ethylene glycol) (PLGA-PEG) nanoparticles (NPs), a type of polymeric NPs, loaded with IR780, a near-infrared (NIR) dye, and doxorubicin (DOX) as the chemotherapeutic drug, were assembled by an improved double emulsification method (designated as IDNPs). The characterization, intracellular uptake, biosafety, photoacoustic (PA) imaging performance, and biodistribution of IDNPs were studied. Chemo-photothermal therapeutic effect and immunogenic cell death (ICD) were evaluated both in vitro and in vivo. The potency of chemo-photothermal therapy-triggered ICD in combination with anti-PD-1 immune checkpoint blockade (ICB) immunotherapy in eliciting immune response and treating distant tumors was further investigated.Results: IR780 and DOX were successfully loaded into PLGA-PEG to form the IDNPs, with size of 243.87nm and Zeta potential of -6.25mV. The encapsulation efficiency of IR780 and DOX was 83.44% and 5.98%, respectively. IDNPs demonstrated remarkable on -site accumulation and PA imaging capability toward 4T1 TNBC models. Chemo-photothermal therapy demonstrated satisfactory therapeutic effects both in vitro and in vivo, and triggered ICD efficiently. ICD, in combination with anti-PD-1, provoked a systemic antitumor immune response against distant tumors.Conclusion: Multifunctional IDNPs were successfully synthesized to mediate chemo-photothermal therapy, which combines immu-nogenic cell death with checkpoint blockade to combat TNBC and distant metastasis, showing great promise preclinically and clinically."

基金机构：National Natural Science Foundation of China [82171949]; Chongqing Natural Science Foundation key project [cstc2019jcyj-zdxmX0019]; Chongqing Postgraduate Scientific Research and Innovation project [CYB21166]

基金资助正文："Acknowledgments This work was supported by the National Natural Science Foundation of China (No. 82171949) , Chongqing Natural Science Foundation key project (No. cstc2019jcyj-zdxmX0019) , and Chongqing Postgraduate Scientific Research and Innovation project (No. CYB21166) ."