A Near-Infrared-II Polymer with Tandem Fluorophores Demonstrates Superior Biodegradability for Simultaneous Drug Tracking and Treatment Efficacy Feedback
Dengshuai Wei, Yingjie Yu, Yun Huang, Yuming Jiang, Yao Zhao, Zongxiu Nie, Fuyi Wang, Wen Ma, Zhiqiang Yu, Yuanyu Huang, Xiaodong Zhang, Zhaoqian Liu, Xingcai Zhang, Haihua Xiao
Abstract
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) (1S,2S-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. In vitro, the nanoparticles were approximately 4–1000- and 1.5–10-fold more potent than cisplatin and 56MESS, respectively. Moreover, in vivo, they significantly inhibited tumor growth on a multidrug-resistant patient-derived mouse model (PDXMDR). Finally, through label-free laser desorption-ionization mass spectrometry imaging (MALDI-MSI), in situ 56MESS release in the deeper tumors was observed. This work highlighted the use of biodegradable NIR-II polymers for monitoring drugs in vivo and therapeutic effect feedback in real-time.