Wei Dengshuai, Yu Yingjie, Huang Yun, Jiang Yuming, Zhao Yao, Nie Zongxiu, Wang Fuyi, Ma Wen, Yu Zhiqiang, Huang Yuanyu, Zhang Xiao-Dong, Liu Zhao-Qian, Zhang Xingcai, Xiao Haihua
Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
ACS Nano. 2021 Mar 23;15(3):5428-5438. doi: 10.1021/acsnano.1c00076. Epub 2021 Mar 9.
NIR-II (1000-1700 nm) fluorescence imaging is continually attracting strong research interest. However, current NIR-II imaging materials are limited to small molecules with fast blood clearance and inorganic nanomaterials and organic conjugated polymers of poor biodegradability and low biocompatibility. Here, we report a highly biodegradable polyester carrying tandem NIR-II fluorophores as a promising alternative. The polymer encapsulated a platinum intercalator (56MESS, (5,6-dimethyl-1,10-phenanthroline) (1,2-diaminocyclohexane) platinum(II)) and was conjugated with both a cell-targeting RGD peptide and a caspase-3 cleavable peptide probe to form nanoparticles for simultaneous NIR-II and apoptosis imaging. , the nanoparticles were approximately 4-1000- and 1.5-10-fold more potent than cisplatin and 56MESS, respectively. Moreover, , they significantly inhibited tumor growth on a multidrug-resistant patient-derived mouse model (PDX). Finally, through label-free laser desorption-ionization mass spectrometry imaging (MALDI-MSI), 56MESS release in the deeper tumors was observed. This work highlighted the use of biodegradable NIR-II polymers for monitoring drugs and therapeutic effect feedback in real-time.
近红外二区（1000 - 1700纳米）荧光成像一直吸引着强烈的研究兴趣。然而，目前的近红外二区成像材料仅限于血液清除快的小分子以及生物降解性差和生物相容性低的无机纳米材料和有机共轭聚合物。在此，我们报道了一种带有串联近红外二区荧光团的高生物可降解聚酯作为一种有前景的替代物。该聚合物包裹了一种铂嵌入剂（56MESS，(5,6 - 二甲基 - 1,10 - 菲咯啉)(1,2 - 二氨基环己烷)铂(II)），并与细胞靶向RGD肽和半胱天冬酶 - 3可裂解肽探针共轭，形成用于同时进行近红外二区和细胞凋亡成像的纳米颗粒。该纳米颗粒的效力分别比顺铂和56MESS高约4 - 1000倍和1.5 - 10倍。此外，它们在多药耐药患者来源的小鼠模型（PDX）上显著抑制了肿瘤生长。最后，通过无标记激光解吸 - 电离质谱成像（MALDI - MSI），观察到了56MESS在更深层肿瘤中的释放。这项工作突出了使用可生物降解的近红外二区聚合物进行实时监测药物和治疗效果反馈的应用。
