基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
ROS 敏感纳米载体用于三阴性乳腺癌及其转移的协同 X-PDT/化疗/免疫治疗
英文原题：ROS-sensitive nanocarriers for synergistic X-PDT/chemo/immunotherapy of triple-negative breast cancer and metastasis.
查看英文原题
ROS-sensitive nanocarriers for synergistic X-PDT/chemo/immunotherapy of triple-negative breast cancer and metastasis.
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中文摘要
X 射线诱导的光动力疗法（X-PDT）因其不受限的组织穿透深度而在肿瘤治疗中展现出巨大前景，但需要将增敏剂递送至肿瘤。在此，我们设计了一种包裹光敏剂维替泊芬（VP）和 T 淋巴细胞活化杀伤细胞来源蛋白激酶（TOPK）抑制剂 OTS964 的聚合物纳米载体（VP/OTS964@NPs），用于有效的肿瘤 X-PDT、分子靶向治疗，并在与 PD-L1 阻断联合时诱导强效抗肿瘤免疫，以实现低免疫原性乳腺肿瘤及其肺转移的协同免疫治疗。VP/OTS964@NPs 呈单分散状态，可响应肿瘤微环境中高水平的活性氧（ROS）或 X-PDT 过程中产生的 ROS 而解组装释放药物。它能高效地将药物递送至 TOPK 高表达乳腺癌细胞，产生 ROS 并诱导 ICD 效应。通过 i.v. 注射，VP/OTS964@NPs 可高效蓄积于乳腺肿瘤中，并在 X-PDT 作用下有效根除肿瘤。
此外，VP/OTS964@NPs 可激活全身性抗肿瘤免疫应答，显著抑制远端乳腺肿瘤及乳腺肿瘤肺转移，并在与 PD-L1 阻断联合时提高生存率。
本研究提出了一种用于协同分子治疗、肿瘤 XDT 和免疫治疗的纳米载体工程化策略。意义声明：X-PDT 是一种有前景的癌症治疗手段。
然而，其临床应用受到合适增敏剂有限及其肿瘤靶向能力不足的制约。本研究旨在构建共载光敏剂维替泊芬和TOPK抑制剂OTS964的ROS敏感纳米载体，以实现对三阴性乳腺癌的协同X-PDT。通过进一步激活抗肿瘤免疫应答，该策略旨在抑制远端及转移性乳腺肿瘤。
总体而言，本研究为低免疫原性实体瘤的治疗提供了纳米药物平台和治疗策略。
展开英文摘要原文
X-ray-induced photodynamic therapy (X-PDT) shows significant promise in tumor treatments due to its unlimited tissue penetration but requires delivering sensitizers to tumors.
Here, we engineered photosensitizer verteporfin (VP) and T-lymphokine-activated killer cell-originated protein kinase (TOPK) inhibitor OTS964-encapsulated polymeric nanocarriers (VP/OTS964@NPs) for effective tumor X-PDT, molecule-targeted therapy and inducing robust antitumor immunity for synergistic immunotherapy of low immunogenic breast tumors and their lung metastases when combined with PD-L1 blockade.
The VP/OTS964@NPs are monodisperse and can be disassembled to release drugs in response to high reactive oxygen species (ROS) levels in the tumor microenvironment or generated during X-PDT. It can efficiently deliver drugs into the TOPK-high expression breast cancer cells, generate ROS and induce ICD effects. By i. v. injection, VP/OTS964@NPs efficiently accumulated in the breast tumors and effectively eradicated tumors upon X-PDT.
Additionally, the VP/OTS964@NPs activated the systemic antitumor immune responses, significantly inhibited the distant breast tumors and the lung metastasis of breast tumors, and enhanced the survival rates in combination with PD-L1 blockade.
This study presented a strategy for engineering nanocarriers for synergistic molecular therapy, tumor XDT and immunotherapy. STATEMENT OF SIGNIFICANCE: X-PDT is a promising therapeutic modality for cancer treatment.
However, its clinical application is hindered by the limited availability of suitable sensitizers and their insufficient tumor-targeting capability. This work aims to construct ROS-sensitive nanocarriers co-loaded with the photosensitizer verteporfin and the TOPK inhibitor OTS964 to achieve synergistic X-PDT for triple-negative breast cancer. By further activating antitumor immune responses, this strategy is designed to suppress the distant and metastatic breast tumors.
Overall, this work provides both a nanodrug platform and a therapeutic strategy for the treatment of poorly immunogenic solid tumors.
论文信息
- 作者
- Wei C、Feng L、Liu J、Xu M、Cui Y、Lin F、Yu H、Feng Z
- 第一作者单位
- Department of Radiology, Huaxi MR Research Center (HMRRC), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No.17 South Renmin Road, Chengdu, Sichuan, 610041, China.China
- 通讯作者单位
- Department of Radiology, Huaxi MR Research Center (HMRRC), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No.17 South Renmin Road, Chengdu, Sichuan, 610041, China; College of Polymer Science and Engineering, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: mi@scu.edu.cn.China
- 期刊
- Acta biomaterialia2026 Jan
- 原文标识
- PubMed 41412288 · DOI 10.1016/j.actbio.2025.12.035