Near-Infrared Fluorescent and Magnetic Resonance Dual-Imaging Coacervate Nanoprobes for Trypsin Mapping and Targeted Payload Delivery of Malignant Tumors

Abstract

Trypsin-responsive near-infrared fluorescent (NIRF) and magnetic resonance (MR) dual-imaging composite nanoparticle/polypeptide coacervate nanoprobes with tunable sizes, have been constructed herein via electrostatic interaction-induced self-assembly. Considering the requirements of in vivo metabolism on nanoparticle size, three coacervate nanoprobes with diameters of around 100, 200, and 300 nm were fabricated with a polydispersity of around 0.2. These coacervate nanoprobes consist of Fe3O4 magnetic nanoparticles surface-decorated with poly acrylic acid and Cy5.5-modified poly-l-lysine (PLL-g-Cy5.5) serving as MR imaging and trypsin-responsive substrate/NIRF agents, respectively. The notable fluorescence signal from PLL-g-Cy5.5 is self-quenched due to the short distances between the fluorescent Cy5.5 molecules after construction of the coacervate nanoprobes. Remarkably, coacervate nanoprobes with a diameter of around 100 nm are selectively disintegrated into fragmented segments upon the hydrolysis of PLL by trypsin, resulting in an 18-fold amplification of the NIRF intensity in comparison with the self-assembled coacervate nanoprobes in the quenched state. Moreover, the MR imaging enhancement is also related to the disintegration of the coacervate nanoprobes. Cellular experiments and in vivo studies demonstrate that the coacervate nanoprobes exhibit remarkable trypsin-sensitive NIRF and MR dual-imaging capabilities and thus have excellent potential to serve as dual-imaging nanoprobes for the efficient mapping of malignant tumors in which trypsin is often overexpressed. In consideration of their excellent capability to enrich charged molecules, the coacervate nanoprobes provide a conceptually novel and promising platform toward in vivo trypsin mapping and controlled delivery of targeted payloads.

Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications

“…Near-infrared fluorescent (NIRF) and magnetic resonance dual-imaging coacervate nanoprobes were designed for trypsin mapping and targeted payload delivery of malignant tumors by Guo et al [ 167 ] ( Figure 12 ). These nanoprobes are composed of Fe 3 O 4 magnetic nanoparticles whose surface is decorated with polyacrylic acid and Cy5.5-modified poly- d / l -L (P- d / l -L-g-Cy5.5) leading to MR imaging and trypsin-responsive substrate/NIRF agents, respectively.…”

“… MR imaging and trypsin-responsive substrate/NIRF agents composed of Fe 3 O 4 magnetic nanoparticles whose surface is decorated with polyacrylic acid and Cy5.5-modified poly- d / l -L (P- d / l -L-g-Cy5.5). Reprinted with permission from Reference [ 167 ]. …”

Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application

“…Drug delivery to tumor sites and the therapeutic responses could be monitored in tumor-bearing nude mice injected with RGD-f-PNPs/EPI through near-infrared fluorescence imaging. Self-assembly of cy5.5-modifed poly-L-lysine (PLLs-g-Cy5.5) and PAA decorated Fe3O4 magnetic nanoparticles (MNPs@PAA) through electrostatic interactions, in the presence of crosslinker, produced NPs for NIR fluorescence and magnetic resonance imaging (MRI) ( Figure 21) [202]. The trypsin-responsive nanoparticles selectively disintegrated upon hydrolysis of PLL by trypsin, resulting in an 18-fold amplification of the NIR fluorescence and the enhancement of the MRI signal.…”

“… Self-assembly and trypsin-initiated disintegration of the nanoparticles for trypsin mapping of malignant tumors via NIR fluorescence and MR dual imaging. Adapted from [ 202 ], with permission. Copyright: 2020 American Chemical Society.…”

Engineering Intelligent Nanosystems for Enhanced Medical Imaging

“…While many efforts are dedicated to sensing pH and hydrogen peroxide, many more biomedically relevant analytes may be measured, such as levels of ions, [63,[234][235][236][237] reactive oxygen or nitrogen species, [238][239][240][241][242][243][244][245][246] enzymes, [81,[247][248][249][250][251][252][253][254] glutathione, [255][256][257][258][259][260] and other biomarkers. [261][262][263] An example is the ratiometric hypochlorite sensor developed by Zou et al for the detection of arthritis ( Figure 11A).…”