Abstract
Purpose. To develop an L-PG-based imaging probe suitable for assessing the degradation of L-PG in vivo. Materials and Methods. Conjugates of L-PG and a near-infrared fluorescence (NIRF) dye, NIR813, were characterized with regard to quenching efficiency and degradability by cathepsin B (CB) and other proteases. The kinetics of L-PG-NIR813's degradation and its degradation in orthotopic human U87/TGL glioma in nude mice after intravenous injection was assessed using NIRF optical imaging (n=3). Results. The fluorescence signal from L-PG-NIR813 was efficiently quenched and activated at NIR813 loadings of 8-10%. Upon exposure to CB, the fluorescence intensity of L-PG-NIR813 increased 10-fold. L-PG-NIR813 was also degraded by another cysteine protease cathepsin L, but not by MMP-2, cathepsin E, cathepsin D, and plasmin. A selective CB inhibitor blocked the fluorescence activation. After intravenous injection, the degradation of L-PG-NIR813 was visualized primarily in the liver, which peaked at 4 h postinjection. Activation of L-PG-NIR813 but not D-PG-NIR813 was clearly seen in U87/TGL tumors. Conclusion. Our results indicate that L-PG-NIR813 may be used to monitor the in vivo degradation of L-PG-based polymeric drugs, and that this agent may prove useful in noninvasive imaging of protease activity, particularly that of cysteine proteases.
Original language | English (US) |
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Pages (from-to) | 1217-1224 |
Number of pages | 8 |
Journal | Pharmaceutical Research |
Volume | 24 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2007 |
Keywords
- Biodegradation
- Cathepsin B
- Molecular imaging
- Near-infrared optical imaging
- Poly(L-glutamic acid)
ASJC Scopus subject areas
- Biotechnology
- Molecular Medicine
- Pharmacology
- Pharmaceutical Science
- Organic Chemistry
- Pharmacology (medical)
MD Anderson CCSG core facilities
- Small Animal Imaging Facility