Towards more accurate bioimaging of drug nanocarriers: turning aggregation-caused quenching into a useful tool

One of the current challenges in the monitoring of drug nanocarriers lies in the difficulties in discriminating the carrier-bound signals from the bulk signals of probes. Environment-responsive probes that enable signal switching are making steps towards a solution to this problem. Aggregation-caused quenching (ACQ), a phenomenon generally regarded as unfavorable in bioimaging, has turned out to be a promising characteristic for achieving environment-responsiveness and eliminating free-probe interference. So-called ACQ probes emit fluorescence when dispersed molecularly within the carrier matrix but quench immediately and absolutely once they are released into the ambient aqueous environment upon the degradation of the nanocarriers. Therefore, the fluorescence observed represents integral nanocarriers. Based on this rationale, the in vivo fates of various nanocarriers have been explored using live imaging equipment, with very interesting findings revealing the role of the particles. The current applications are however restricted to nanocarriers with highly hydrophobic matrices (lipid or polyester nanoparticles) or with a hydrophobic core-hydrophilic shell structure (micelles). The ACQ-based bioimaging strategy is emerging as a promising tool to achieve more accurate bioimaging of drug nanocarriers. This review article provides an overview of the ACQ phenomenon and the rationale for and examples of applications, as well as the limitations of the ACQ-based strategy, with a focus on improving the accuracy of bioimaging of nanoparticles.