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光激活乏氧敏感仿生型诱饵高效级联用于乳腺癌的光动力-化学治疗。

Light-activated hypoxia-sensitive biomimetic decoy efficiently cascading photodynamic-chemo therapy for breast cancer.

机构信息

Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Department of Oncology, Pinghu Second People's Hospital, Zhapu Town, Jiaxing City, Zhejiang Province, China.

出版信息

Colloids Surf B Biointerfaces. 2024 Nov;243:114145. doi: 10.1016/j.colsurfb.2024.114145. Epub 2024 Aug 6.

DOI:10.1016/j.colsurfb.2024.114145
PMID:39142000
Abstract

The hypoxic microenvironment within the tumor microenvironment of breast cancer imposes a challenge in overcoming chemotherapy resistance. In this investigation, we designed a novel strategy utilizing a light-controlled cascade targeting nanomedicine specifically tailored for enhanced immune therapy of breast cancer. Albumin nanoparticle was achieved by crosslinking, followed by loading TPZ and Ce6, and subsequent modification to enable selective binding with CD44 hyaluronic acid to form nanomedicine. Encouragingly, it was demonstrated the remarkable ability of the nanomedicine to effectively internalize into cellular entities, thereby inducing apoptosis in 4T1 cells efficiently in vitro when exposed to light irradiation. In vivo assessments showcased the exceptional aptitude of the nanomedicine not only for preferential accumulation within tumor tissues, but also for substantial suppression of tumor growth. Immune mechanisms have shown that nanomedicine treatment promoted the maturation of DCs in vivo, enhanced the proportion of CD8 T cells in the spleen and tumor, and simultaneously upregulated the ratio of M1 macrophages favorable for anti-tumor effects. These outcomes collectively advance a fresh perspective for the clinical breast cancer therapy.

摘要

乳腺癌肿瘤微环境中的缺氧微环境给克服化疗耐药性带来了挑战。在这项研究中,我们设计了一种利用光控级联靶向纳米医学的新策略,专门用于增强乳腺癌的免疫治疗。白蛋白纳米颗粒通过交联实现,然后负载 TPZ 和 Ce6,随后进行修饰以实现与透明质酸 CD44 的选择性结合,形成纳米药物。令人鼓舞的是,该纳米药物具有高效内化进入细胞实体的显著能力,从而在体外光照照射下有效地诱导 4T1 细胞凋亡。体内评估展示了该纳米药物不仅在肿瘤组织中优先积累,而且还能显著抑制肿瘤生长的卓越能力。免疫机制表明,纳米药物治疗促进了体内 DC 的成熟,提高了脾和肿瘤中 CD8 T 细胞的比例,同时上调了有利于抗肿瘤作用的 M1 巨噬细胞的比例。这些结果共同为临床乳腺癌治疗提供了新的视角。

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