Nguyen Lam-Duc-Huy, Cheng Sheng-Liang, Yen Yu-Ting, Lee Hsin-Mei, Wu Te-Haw, Wang Jane, Lin Shu-Yi, Chen Yunching
Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan.
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 34881, Taiwan.
Adv Sci (Weinh). 2025 Jul 11:e03238. doi: 10.1002/advs.202503238.
Triple-negative breast cancer (TNBC) is an aggressive malignancy with high mortality and limited treatment options. While surgical resection removes the primary tumor, it often fails to prevent recurrence or metastasis, and despite the promise of immunotherapy, response to immune checkpoint blockade remains poor. Here, a cryogel-based dendritic cell (DC) immunotherapy is developed incorporating gold nanodot-lipopolysaccharide (AuLPS)-loaded DCs, doxorubicin (Dox), and PD-1 immune checkpoint blockade (aPD-1+Dox+AuLPS@DC) to enhance post-surgical antitumor immunity. The AuLPS nanoparticles (NPs) stabilize LPS assembly, optimizing Th1 adjuvant activity and improving DC immunotherapy efficacy while minimizing adverse effects. The cryogel enables the sustained, localized release of therapeutic agents at the surgical site, preserving DC viability, migration, and functionality within the tumor microenvironment. This strategy enhances DC activation and potentiates robust T-cell activation in both tumor-draining lymph nodes and tumor beds, leading to durable antitumor immunity. When administered at the post-surgical site in an orthotopic TNBC model, the aPD-1+Dox+AuLPS@DC cryogel immunotherapy significantly delays tumor recurrence, reduces distant metastasis, and prolongs survival. These findings highlight cryogel-based DC immunotherapy as a promising post-surgical therapeutic strategy to enhance responses to immune checkpoint blockade and improve outcomes in TNBC.
