Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, CAS Key Lab for Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, China.
Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, CAS Key Lab for Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Biomaterials. 2018 Sep;177:149-160. doi: 10.1016/j.biomaterials.2018.05.051. Epub 2018 May 31.
Metastatic triple-negative breast cancer (mTNBC) is an aggressive disease among women worldwide, characterized by high mortality and poor prognosis despite systemic therapy with radiation and chemotherapies. Photodynamic therapy (PDT) is an important strategy to eliminate the primary tumor, however its therapeutic efficacy against metastases and recurrence is still limited. Here, we employed a template method to develop the core-shell gold nanocage@manganese dioxide (AuNC@MnO, AM) nanoparticles as tumor microenvironment responsive oxygen producers and near-infrared (NIR)-triggered reactive oxygen species (ROS) generators for oxygen-boosted immunogenic PDT against mTNBC. In this platform, MnO shell degrades in acidic tumor microenvironment pH/HO conditions and generates massive oxygen to boost PDT effect of AM nanoparticles under laser irradiation. Fluorescence (FL)/photoacoustic (PA)/magnetic resonance (MR) multimodal imaging confirms the effective accumulation of AM nanoparticles with sufficient oxygenation in tumor site to ameliorate local hypoxia. Moreover, the oxygen-boosted PDT effect of AM not only destroys primary tumor effectively but also elicits immunogenic cell death (ICD) with damage-associated molecular patterns (DAMPs) release, which subsequently induces DC maturation and effector cells activation, thereby robustly evoking systematic antitumor immune responses against mTNBC. Hence, this oxygen-boosted immunogenic PDT nanosystem offers a promising approach to ablate primary tumor and simultaneously prevent tumor metastases via immunogenic abscopal effects.
转移性三阴性乳腺癌（mTNBC）是一种在全球范围内威胁女性健康的侵袭性疾病，尽管采用放疗和化疗等系统疗法，但其死亡率和预后仍较差。光动力疗法（PDT）是消除原发性肿瘤的重要策略，但其对转移和复发的治疗效果仍然有限。在这里，我们采用模板法制备了核壳型金纳米笼@二氧化锰（AuNC@MnO，AM）纳米颗粒作为肿瘤微环境响应性氧产生剂和近红外（NIR）触发的活性氧（ROS）发生器，用于增强 mTNBC 的免疫原性 PDT。在该平台中，MnO 壳在酸性肿瘤微环境 pH/HO 条件下降解并产生大量氧气，在激光照射下增强 AM 纳米颗粒的 PDT 效应。荧光（FL）/光声（PA）/磁共振（MR）多模态成像证实 AM 纳米颗粒在肿瘤部位有效积聚并充分氧合，以改善局部缺氧。此外，AM 的氧增强 PDT 效应不仅能有效破坏原发性肿瘤，还能引发免疫原性细胞死亡（ICD）和损伤相关分子模式（DAMPs）释放，进而诱导 DC 成熟和效应细胞激活，从而强烈引发针对 mTNBC 的系统性抗肿瘤免疫反应。因此，这种氧增强免疫原性 PDT 纳米系统为消融原发性肿瘤并通过免疫原性远隔效应同时预防肿瘤转移提供了一种有前途的方法。
