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Updated: Jul 16, 2026
Injectable Supramolecular Polymer-Nanoparticle Hydrogels for Cell and Drug Delivery Applications
Published on: February 7, 2021
A novel method for imaging in vivo degradation of poly(L-glutamic acid), a biodegradable drug carrier
Marites P Melancon1, Wei Wang, Yuetang Wang
1Department of Experimental Diagnostic Imaging-Box 57, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA, cli@di.mdacc.tmc.edu.
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.
