A Comprehensive Strategy Based on High Clinical Translational Nanosystem for Programmable Immunotherapy of Triple Negative Breast Cancer

Meng Meng; Jiayan Wu; Yuanji Feng; Lin Lin; Jie Chen; Xuan Pang; Yanhui Li; Kai Hao; Huayu Tian; Xuesi Chen

doi:10.1002/adma.202314309

A Comprehensive Strategy Based on High Clinical Translational Nanosystem for Programmable Immunotherapy of Triple Negative Breast Cancer

Adv Mater. 2024 Mar 23:e2314309. doi: 10.1002/adma.202314309. Online ahead of print.

Authors

Meng Meng^{1

2}, Jiayan Wu^{1

2}, Yuanji Feng³, Lin Lin^{1

2}, Jie Chen^{1

2}, Xuan Pang^{1

2}, Yanhui Li⁴, Kai Hao³, Huayu Tian^{1

2

3

5}, Xuesi Chen^{1

2}

Affiliations

¹ Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
² School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China.
³ State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
⁴ School of Materials Science and Engineering, Xiamen University of Technology, Xiamen, 361024, China.
⁵ Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen, 361005, China.

PMID: 38520284
DOI: 10.1002/adma.202314309

Abstract

Triple negative breast cancer (TNBCs), known as an immunologically cold tumor, is difficult to completely eliminate with existing monotherapies, let alone metastasis and recurrence. It is urgent to design a rational combination of multiple therapies to programmatically reconstitute tumor microenvironment (TME) and reverse the immune "cold" into "hot" inflammatory tumors to improve the therapeutic effect. Hence, in this work, a multifunctional nanosystem (FeSH NPs) that integrates metal-polyphenol coordination complex as a photothermal agent and polyphenol, salvianolic acid B (SAB) as immunomodulator is designed and fabricated for synergistic photothermal-immunotherapy of TNBCs combined with anti-PD-L1 antibody. Guided by photothermal/photoacoustic dual-mode imaging, photothermal therapy (PTT) caused by FeSH NPs induces immunogenic cell death (ICD) under 808 nm laser irradiation. Subsequently, the loaded SAB is released with the addition of deferoxamine mesylate (DFO) to remodel TME, specifically TGF-β inhibition and PD-L1 upregulation, and eliminate the primary tumors. The combination of PTT and TME reprogramming by FeSH NPs further synergizes with anti-PD-L1 antibody to eradicate recurrence and inhibit metastasis of TNBCs concurrently. Given the biosafety of FeSH NPs throughout the lifecycle, this work provides a protocol with high clinical translational promise for comprehensive programmed therapeutics of immunologically cold tumors TNBCs.

Keywords: immune checkpoint blockade; programmable photothermal‐immunotherapy; transforming growth factor β; triple negative breast cancer; tumor microenvironment reprogramming.

Abstract

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