Dual activatable self-assembled nanotheranostics for bioimaging and photodynamic therapy
作者：Yan Fu，Moon-Sun Jang，Nannan Wang，Yi Li，Te Peng Wu，Jung Hee Lee，Doo Sung Lee，Hong Yu Yang
關鍵字：PDT
論文來源：期刊
具體來源：https://doi.org/10.1016/j.jconrel.2020.07.045
發表時間：2020年
Multifunctional nanosystems that can transport therapeutic and diagnostic agents into tumor sites and activate their respective functions via tumor-microenvironment recognition are highly desirable for clinical applications. We fabricated pH and redox dual-activatable self-assembled nanotheranostics (named as DA-SNs) via coordination-driven self-assembly of chlorin e6 (Ce6) disulfide-linked pH sensitive polymer ligand, poly (isobutylene-alt-maleic anhydride-graft-methoxy-poly (ethyleneglycol)-graft-imidazole-graft-Cystamine-Ce6) [PIMA-mPEG-API-SS-Ce6], and gadolinium ions (Gd3+). DA-SNs exhibited uniform particle size of ~48 nm, excellent stability, and inherent biosafety. Negatively charged DA-SNs could prolong blood circulation time (t1/2 = 2.91 h) and improve tumor accumulation. Moreover, DA-SNs could undergo surface charge switch from negative charge to positive one in a slightly acidic tumor extracellular environment (pH 6.8), thus enhancing cellular uptake. After entering tumor cells, fluorescence, photodynamic therapeutic activity, and T1MR contrast from DA-SNs could be activated within this intracellular environment with lowered pH and high level of GSH. Importantly, human tumors implanted in mice could be successfully visualized via distinct pH and redox dual-sensitive T1MR contrast and fluorescence imaging, indicating that DA-SNs could serve as a dual-modal MR/fluorescence imaging probe for tumor-targeting diagnosis. In addition, DA-SNs exhibited superior photodynamic therapeutic efficiency with negligible side effects. Therefore, this DA-SN shows great promise for synergistic photodynamic therapy and diagnostic imaging.