Combination of MHI148 Targeted Photodynamic Therapy and STING Activation Inhibits Tumor Metastasis and Recurrence

作者全名：Yu, Huilin; Chen, Qiaoqi; Zheng, Min; Wang, Ruoyao; Wang, Haiyang; Cheng, Long; Hu, Yaqin; Dai, Mingyuan; Du, Chier; Luo, Wenpei; Tan, Mixiao; Cao, Yang; Guo, Yuan; Ran, Haitao

作者地址：[Yu, Huilin; Chen, Qiaoqi; Zheng, Min; Cheng, Long; Hu, Yaqin; Dai, Mingyuan; Du, Chier; Luo, Wenpei; Tan, Mixiao; Guo, Yuan; Ran, Haitao] Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, Chongqing 400010, Peoples R China; [Yu, Huilin; Chen, Qiaoqi; Zheng, Min; Wang, Ruoyao; Wang, Haiyang; Cheng, Long; Hu, Yaqin; Dai, Mingyuan; Du, Chier; Luo, Wenpei; Tan, Mixiao; Cao, Yang; Guo, Yuan; Ran, Haitao] Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China; [Yu, Huilin; Chen, Qiaoqi; Zheng, Min; Wang, Ruoyao; Wang, Haiyang; Cheng, Long; Hu, Yaqin; Dai, Mingyuan; Du, Chier; Luo, Wenpei; Tan, Mixiao; Cao, Yang; Guo, Yuan; Ran, Haitao] Chongqing Med Univ, State Key Lab Ultrasound Med & Engn, Chongqing 400010, Peoples R China; [Wang, Ruoyao] Chongqing Med Univ, Affiliated Hosp 2, Dept Breast & Thyroid Surg, Chongqing 400010, Peoples R China; [Wang, Haiyang] Chongqing Med Univ, Affiliated Hosp 2, Dept Abdominal Wall Hernia & Vasc Surg, Chongqing 400010, Peoples R China

通信作者：Guo, Y; Ran, HT (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, Chongqing 400010, Peoples R China.; Guo, Y; Ran, HT (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China.; Guo, Y; Ran, HT (通讯作者)，Chongqing Med Univ, State Key Lab Ultrasound Med & Engn, Chongqing 400010, Peoples R China.

来源：ACS APPLIED MATERIALS & INTERFACES

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001237806500001

JCR分区：Q1

影响因子：8.3

年份：2024

卷号：16

期号：23

开始页：29672

结束页：29685

文献类型：Article

关键词：photodynamic immunotherapy; stimulator of interferongenes agonist; nanomedicine; breast cancer; metastasis and recurrence

摘要：Metastasis and recurrence are notable contributors to mortality associated with breast cancer. Although immunotherapy has shown promise in mitigating these risks after conventional treatments, its effectiveness remains constrained by significant challenges, such as impaired antigen presentation by dendritic cells (DCs) and inadequate T cell infiltration into tumor tissues. To address these limitations, we developed a multifunctional nanoparticle platform, termed GM@P, which consisted of a hydrophobic shell encapsulating the photosensitizer MHI148 and a hydrophilic core containing the STING agonist 2 ' 3 '-cGAMP. This design elicited robust type I interferon responses to activate antitumor immunity. The GM@P nanoparticles loaded with MHI148 specifically targeted breast cancer cells. Upon exposure to 808 nm laser irradiation, the MHI148-loaded nanoparticles produced toxic reactive oxygen species (ROS) to eradicate tumor cells through photodynamic therapy (PDT). Notably, PDT stimulated immunogenic cell death (ICD) to foster the potency of antitumor immune responses. Furthermore, the superior photoacoustic imaging (PAI) capabilities of MHI148 enabled the simultaneous visualization of diagnostic and therapeutic procedures. Collectively, our findings uncovered that the combination of PDT and STING activation facilitated a more conducive immune microenvironment, characterized by enhanced DC maturation, infiltration of CD8(+) T cells, and proinflammatory cytokine release. This strategy stimulated local immune responses to augment systemic antitumor effects, offering a promising approach to suppress tumor growth, inhibit metastasis, and prevent recurrence.

基金机构：Chongqing Postdoctoral Science Foundation [82071926, 82302210, 82102053]; National Natural Science Foundation of China [2022MD713714]; China Postdoctoral Science Foundation [2021XM3111, CSTB2022NSCQ-BHX0620]; Chongqing Postdoctoral Science Foundation

基金资助正文：The authors sincerely acknowledge the financial support from the National Natural Science Foundation of China (Grant Nos. 82071926, 82302210, and 82102053), China Postdoctoral Science Foundation funded project (Grant No. 2022MD713714), and Chongqing Postdoctoral Science Foundation funded projects (Grant No. 2021XM3111 and CSTB2022NSCQ-BHX0620).