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基于冷冻凝胶的树突状细胞免疫疗法用于乳腺癌术后治疗

英文原题:Cryogel-Based Dendritic Cell Immunotherapy for Post-Surgical Breast Cancer Treatment.

查看英文原题

Cryogel-Based Dendritic Cell Immunotherapy for Post-Surgical Breast Cancer Treatment.

PubMed 2025/07/11(内容时间) Adv Sci (Weinh) Q1 · IF 14.1(JCR 2025)

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中文摘要

三阴性乳腺癌(TNBC)是一种侵袭性恶性肿瘤,死亡率高且治疗选择有限。虽然手术切除可去除原发肿瘤,但往往无法阻止复发或转移,且尽管免疫治疗前景可期,对免疫检查点阻断的应答仍然不佳。

在此,我们开发了一种基于冷冻凝胶的树突状细胞(DC)免疫疗法,该疗法整合了负载金纳米点-脂多糖(AuLPS)的DC、多柔比星(Dox)和PD-1免疫检查点阻断(aPD-1+Dox+AuLPS@DC),以增强术后抗肿瘤免疫。AuLPS纳米颗粒(NPs)可稳定LPS组装,优化Th1佐剂活性并提高DC免疫疗法疗效,同时最大限度减少不良反应。冷冻凝胶能够在手术部位持续、局部释放治疗药物,维持DC在肿瘤微环境中的活力、迁移和功能。该策略增强DC活化,并在肿瘤引流淋巴结和肿瘤床中均能激发强效的T细胞活化,从而产生持久的抗肿瘤免疫。在原位TNBC模型的术后部位给药时,aPD-1+Dox+AuLPS@DC冷冻凝胶免疫疗法可显著延缓肿瘤复发、减少远处转移并延长生存期。这些发现凸显了基于冷冻凝胶的DC免疫疗法作为一种有前景的术后治疗策略,可增强对免疫检查点阻断的应答并改善TNBC的预后。

展开英文摘要原文

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.

论文信息

作者
Nguyen LD、Cheng SL、Yen YT、Lee HM、Wu TH、Wang J、Lin SY、Chen Y
单位
Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan.Taiwan
期刊
Advanced science (Weinheim, Baden-Wurttemberg, Germany)2025 Oct
原文标识
PubMed 40642931 · DOI 10.1002/advs.202503238