Fluorescence-Shadowing Nanoparticle Clusters for Real-Time Monitoring of Tumor Progression

Abstract

Monitoring tumor progression is important for elucidating appropriate therapeutic strategies in response to anticancer therapeutics. To fluorescently monitor the in vivo levels of tumor-specific enzymes, we prepared matrix metalloprotease (MMP)-responsive gold nanoparticle (AuNP) clusters to sense tumor microenvironments. Specifically, AuNPs and quantum dots (QDs) were surface-engineered with two poly(ethylene glycol)[PEG] shells and cyclooctyne moieties, respectively, for the copper-free click reaction. Upon "peeling off" of the secondary shell from the double-PEGylated AuNPs under MMP-rich conditions, shielded azide moieties of the AuNPs were displayed toward the QD, and those two particles were clicked into nanoparticle clusters. This consequently resulted in a dramatic size increase and fluorescence quenching of QDs via fluorescence energy transfer (FRET) due to the molecular proximity of the particles. We observed that FRET efficiency was modulated via changes in MMP levels and exposure time. Cancer cell numbers exhibited a strong correlation with FRET efficiency, and in vivo studies that employed solid tumor models accordingly showed that FRET efficiency was dependent on the tumor size. Thus, we envision that this platform can be tailored and optimized for tumor monitoring based on MMP levels in solid tumors.

Plasmonic quenching and enhancement: metal–quantum dot nanohybrids for fluorescence biosensing

“…A to D adapted with permission from ref. [87] Copyright 2022 American Chemical Society. (E) Schematic principle of a QD-AuNP NSET aptasensor for AMP quantification.…”

“…In one recent study, Yoo et al developed a rather unconventional NSET strategy, which employed target-specific in vitro and in vivo click chemistry for switching QD PL. 87 The NSET system consisted of AuNPs (diameter ∼27 nm) as acceptors and CdSSe/ZnS QDs ( λ em ∼ 520 nm) as donors (Fig. 6A).…”

Reactive oxygen species-responsive clicked assembly of gold nanoparticles to enhance photothermal therapy

“…Previous studies confirmed that AuNPs have a specific plasmon absorbance at approximately 520 nm; this peak can be red-shifted due to the increase in size by PEGylation, and the degree of PEGylation and the length of the decorated PEG can influence the red shift. 23,30 Although the FE-TEM images revealed a smaller particle size due to the collapsed PEG chains, combining the hydrodynamic size and spectroscopic results, it is clear that bare AuNPs were surface-engineered with double layers of PEG shells. 23…”

“…23,30 Although the FE-TEM images revealed a smaller particle size due to the collapsed PEG chains, combining the hydrodynamic size and spectroscopic results, it is clear that bare AuNPs were surface-engineered with double layers of PEG shells. 23…”

“…Under the overexpression of MMP at the tumor site, the secondary PEG shell was de-shielded, and the exposed azide moieties were directed towards the quantum dots, which enabled a click reaction between these two particles into nanoclusters. 23…”