Journal
THERANOSTICS
Volume 11, Issue 14, Pages 7045-7056Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.60586
Keywords
gamma-glutamyl transpeptidase; near-infrared probe; self-assembly; photothermal therapy; tumor microenvironment
Categories
Funding
- National Science Foundation of China [81601531, 81771900, 81971738]
- National Key Research and Development Program of China [2016YFA0203600]
- Double First-Class University Project [CPU2018GY24]
- 16th Six Talent Peaks Project of Jiangsu Province [SWYY-063]
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A GGT-responsive near-infrared nanoassembly was developed for tumor-specific imaging and therapy, showing excellent responsiveness and therapeutic efficacy in tumor cells.
Rationale: Precise treatment of tumors is attracting increasing attention. Molecular probes simultaneously demonstrating the diagnostic signal and pharmacological effect in response to tumor microenvironment are highly desired. gamma-glutamyl transpeptidase (GGT) is a biomarker with significantly up-regulated expression in the tumor area. We developed a GGT responsive near-infrared (NIR) nanoassembly for tumor-specific fluorescence imaging-guided photothermal therapy. Methods: The GGT responsive NIR probe was constructed by conjugating GGT-specific substrate gamma-glutamic acid (gamma-Glu) with cyanine fluorophore (NRh-NH2) via amide reaction. The resulting NRh-G spontaneously assembled into nanoparticles (NRh-G-NPs) around 50 nm. The NPs were characterized and the properties evaluated in the presence or absence of GGT. Subsequently, we studied fluorescence imaging and photothermal therapy of NRh-G-NPs in vitro and in vivo. Results: NRh-G-NPs, upon specific reaction with GGT, turned into NRh-NH2-NPs, showing a similar to 180-fold fluorescence enhancement and excellent photothermal effect recovery. NRh-G-NPs could selectively light up U87MG tumor cells while their fluorescence was weak in L02 human normal liver cells. The NPs also showed excellent tumor cell ablation upon laser irradiation. After intravenous injection into tumor-bearing mice, NRh-G-NPs could arrive in the tumor area and specifically light up the tumor. Following laser irradiation, the tumor could be completely erased with no tumor reoccurrence for up to 40 days. Conclusions: NRh-G-NPs were specifically responsive to GGT overexpressed in U87MG tumor cells and selectively lit up the tumor for imaging-guided therapy. Besides, the recovery of photothermal property in the tumor area could improve cancer therapy precision and decreased side effects in normal tissues.
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