Heavy-Atom-Modulated Supramolecular Assembly Increases Antitumor Potency against Malignant Breast Tumors via Tunable Cooperativity
Heavy-Atom-Modulated Supramolecular Assembly Increases Antitumor Potency against Malignant Breast Tumors via Tunable Cooperativity
复制标题
重原子调制的超分子组装通过可调节的协同性提高了针对恶性乳腺肿瘤的抗肿瘤效力
DOI：
10.1002/adma.202004225
复制
发表时间：
2020-12-03
影响因子：
29.4
通讯作者：
Chen, Huabing
中科院分区：
文献类型：
--
作者：
Guo, Zhengqing;He, Hui;Chen, Huabing
三阴性乳腺癌（TNBC）仍然是女性发病率和死亡率最高的疾病，合理建立针对TNBC的有效治疗方法是一个关键的瓶颈。本研究显示，重原子调制超分子的自组装胶束纳米结构具有高效的细胞质易位和可调节的光转化，可有效抑制原发性、转移性和复发性TNBC。多碘化硼二硝基甲烷胶束产生可调节的光转化为单线态氧和热效应，以及肿瘤的深穿透和随后的细胞质易位。四碘化硼二硝基甲基胶束（4- ibm）通过大量表达凋亡蛋白，有效抑制皮下和原位TNBC模型，并降低氧依赖性，特别显示出明显增强的抗肿瘤效率协同性。此外，与化疗和手术切除相比，4- ibm通过抑制转移相关蛋白、明显的免疫原性细胞死亡和M2巨噬细胞再教育为杀瘤M1表型，产生了更好的抗转移和抗复发效果。这些结果为超分子纳米结构的协同性提供了见解，以有效地光疗TNBC。
Triple-negative breast cancer (TNBC) remains with highest incidence and mortality rates among females, and a critical bottleneck lies in rationally establishing potent therapeutics against TNBC. Here, the self-assembled micellar nanoarchitecture of heavy-atom-modulated supramolecules with efficient cytoplasmic translocation and tunable photoconversion is shown, for potent suppression against primary, metastatic, and recurrent TNBC. Multi-iodinated boron dipyrromethene micelles yield tunable photoconversion into singlet oxygen and a thermal effect, together with deep penetration and subsequent cytoplasmic translocation at the tumor. Tetra-iodinated boron dipyrromethene micelles (4-IBMs) particularly show a distinctly enhanced cooperativity of antitumor efficiency through considerable expressions of apoptotic proteins, potently suppressing subcutaneous, and orthotopic TNBC models, together with reduced oxygen dependence. Furthermore, 4-IBMs yield preferable anti-metastatic and anti-recurrent efficacies through the inhibition of metastasis-relevant proteins, distinct immunogenic cell death, and re-education of M2 macrophages into tumoricidal M1 phenotype as compared to chemotherapy and surgical resection. These results offer insights into the cooperativity of supramolecular nanoarchitectures for potent phototherapy against TNBC.