Hyaluronic acid-functionalized supramolecular nanophotosensitizers for targeted photoimmunotherapy of triple-negative breast cancer.

IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Haiyan Zhang, Hongxin Liu, Zhigang Xie, Jianshi Du, Chunxiang Jin
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引用次数: 0

Abstract

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.

用于三阴性乳腺癌靶向光免疫疗法的透明质酸功能化超分子纳米光敏剂
三阴性乳腺癌(TNBC)被认为是一种特别具有侵袭性的乳腺癌亚型,缺乏有效的治疗靶点。免疫检查点抑制剂(ICIs)在TNBC治疗中显示出有希望的结果。尽管如此,大多数患者要么对ICIs产生耐药性,要么最初对它们没有反应。光免疫治疗因其时空精确性和非侵入性,为TNBC提供了一种靶向治疗策略。在此,我们报道了透明质酸(HA)功能化的吲哚菁绿基超分子纳米粒子(HGI NPs),具有可生物降解的特性,用于TNBC的高性能光声成像和靶向光疗。值得注意的是,由于肿瘤的渗透性和滞留作用增强,以及HA的肿瘤靶向性,HGI NPs可以在TNBC组织中显著聚集。当暴露在808 nm光下时,HGI纳米颗粒的强扩增触发了显著的免疫原性细胞死亡(ICD)反应,从而将免疫抑制的肿瘤微环境(iTME)转变为肿瘤攻击模式和“热”状态。抗肿瘤实验表明,超分子光敏剂HGI NPs对TNBC的清除效率高,生物安全性好。这种协同策略重塑了iTME并增强了抗肿瘤免疫反应,为将光疗和ICIs结合作为TNBC的潜在治疗方法提供了理论基础。
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来源期刊
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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