三重阴性乳腺癌(TNBC)具有特殊的生物学行为和临床病理特征，其具有高侵袭性和转移淋巴结的倾向，导致预后较其他类型乳腺癌差。因此，开发有效的治疗方法对于提高TNBC患者的生存率至关重要。本研究成功制备了一种基于脂质体的治疗诊断纳米系统(ILA@Lip)，同时封装了光敏剂IR 780、抗血管生成剂lentatinib和低氧激活的促细胞凋亡药物AQ4N。ILA@Lip可用于TNBC及其淋巴结转移的近红外(NIR)荧光诊断成像和多模式治疗。ILA@Lip中的lentatinib通过切断氧供应来抑制血管生成，从而增加了缺氧水平。同时，当808 nm激光照射IR 780时，产生大量活性氧(ROS)，此过程也迅速耗尽肿瘤细胞中的氧气，加剧肿瘤缺氧现象。通过在TNBC中创造极度缺氧的环境，非毒性AQ4N转化为剧毒的AQ4的效率更高，用于低氧激活的化疗。ILA@Lip的细胞毒性实验显示与正常细胞和组织相比具有良好的生物相容性，但对于缺氧的乳腺癌细胞具有较高的毒性。此外，通过激光照射治疗的体内瘤肿在皮下瘤模型和原位瘤模型中得到显著抑制。利用ILA@Lip是创造极度缺氧的肿瘤微环境以提高低氧激活化疗的治疗效果的深刻策略，实现了对肿瘤生长的综合抑制，具有临床转化的潜力。© 2023. BioMed Central Ltd., part of Springer Nature.

Triple-negative breast cancer (TNBC) possesses special biological behavior and clinicopathological characteristics, which is highly invasive and propensity to metastasize to lymph nodes, leading to a worse prognosis than other types of breast cancer. Thus, the development of an effective therapeutic method is significant to improve the survival rate of TNBC patients.In this work, a liposome-based theranostic nanosystem (ILA@Lip) was successfully prepared by simultaneously encapsulating IR 780 as the photosensitizer and lenvatinib as an anti-angiogenic agent, together with banoxantrone (AQ4N) molecule as the hypoxia-activated prodrug. The ILA@Lip can be applied for the near-infrared (NIR) fluorescence diagnostic imaging of TNBC and its lymph node metastasis for multimodal therapy. Lenvatinib in ILA@Lip can inhibit angiogenesis by cutting oxygen supply, thereby leading to enhanced hypoxia levels. Meanwhile, large amounts of reactive oxygen species (ROS) were produced while IR 780 was irradiated by an 808 nm laser, which also rapidly exhausted oxygen in tumor cells to worsen tumor hypoxia. Through creating an extremely hypoxic in TNBC, the conversion of non-toxic AQ4N to toxic AQ4 was much more efficiency for hypoxia-activated chemotherapy. Cytotoxicity assay of ILA@Lip indicated excellent biocompatibility with normal cells and tissues, but showed high toxicity in hypoxic breast cancer cells. Also, the in vivo tumors treated by the ILA@Lip with laser irradiation were admirably suppressed in both subcutaneous tumor model and orthotopic tumor models.Utilizing ILA@Lip is a profound strategy to create an extremely hypoxic tumor microenvironment for higher therapeutic efficacy of hypoxia-activated chemotherapy, which realized collective suppression of tumor growth and has promising potential for clinical translation.© 2023. BioMed Central Ltd., part of Springer Nature.