Zhang Haiyan, Liu Hongxin, Xie Zhigang, Du Jianshi, Jin Chunxiang
Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, China.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China.
J Nanobiotechnology. 2024 Dec 19;22(1):777. doi: 10.1186/s12951-024-03044-9.
Triple-negative breast cancer (TNBC) is recognized as a particularly aggressive subtype of breast cancer that is devoid of effective therapeutic targets. Immune checkpoint inhibitors (ICIs) have demonstrated promising results in TNBC treatment. Nonetheless, most patients either develop resistance to ICIs or fail to respond to them initially. Owing to its spatio-temporal precision and non-invasive nature, photoimmunotherapy offers a targeted therapeutic strategy for TNBC. Herein, we report hyaluronic acid (HA)-functionalized indocyanine green-based supramolecular nanoparticles (HGI NPs), with biodegradable characteristics, for high-performance photoacoustic imaging and targeted phototherapy for TNBC. Notably, HGI NPs can significantly gather in TNBC tissues because of the enhanced permeability and retention effect of the tumor, and the tumor-targeting properties of HA. The strong amplification of HGI nanoparticles triggers a significant immunogenic cell death (ICD) response when exposed to 808 nm light, thus shifting the immunosuppressive tumor microenvironment (iTME) into a tumor attack mode and 'hot' state. Antitumor experiments demonstrate the high efficiency of the supramolecular photosensitizers HGI NPs for TNBC elimination and good biosafety. This synergistic strategy reshapes the iTME and amplifies the antitumor immune response, providing a theoretical foundation for combining phototherapy and ICIs as potential treatments for TNBC.
三阴性乳腺癌（TNBC）被认为是一种侵袭性特别强的乳腺癌亚型，缺乏有效的治疗靶点。免疫检查点抑制剂（ICI）在TNBC治疗中已显示出有前景的结果。尽管如此，大多数患者要么对ICI产生耐药性，要么最初就对其无反应。由于其时空精确性和非侵入性，光免疫疗法为TNBC提供了一种靶向治疗策略。在此，我们报道了具有可生物降解特性的、基于透明质酸（HA）功能化吲哚菁绿的超分子纳米颗粒（HGI NPs），用于TNBC的高性能光声成像和靶向光疗。值得注意的是，由于肿瘤的高通透性和滞留效应以及HA的肿瘤靶向特性，HGI NPs可在TNBC组织中显著聚集。当暴露于808 nm光时，HGI纳米颗粒的强烈放大作用会引发显著的免疫原性细胞死亡（ICD）反应，从而将免疫抑制性肿瘤微环境（iTME）转变为肿瘤攻击模式和“热”状态。抗肿瘤实验证明了超分子光敏剂HGI NPs消除TNBC的高效性和良好的生物安全性。这种协同策略重塑了iTME并放大了抗肿瘤免疫反应，为将光疗和ICI联合作为TNBC的潜在治疗方法提供了理论基础。
