Morphology Tuning of Aggregation-Induced Emission Probes by Flash Nanoprecipitation: Shape and Size Effects on in Vivo Imaging

Abstract

Aggregation-induced emission (AIE) imaging probes have recently received considerable attention because of their unique property of high performance in the aggregated state and their imaging capability. However, the tendency of AIE molecules to aggregate into micron long irregular shapes, which significantly limits their application in vivo, is becoming a serious issue that needs to be addressed. Here, we introduce a novel engineering strategy to tune the morphology and size of AIE nanoaggregates, based on flash nanoprecipitation (FNP). Quinolinemalononitrile (ED) is encapsulated inside properly selected amphiphilic block copolymers of varying concentration. This leads to a variety of ED particle morphologies with different sizes. The shape and size are found to have strong influences on tumor targeting both in vitro and in vivo. The current results therefore indicate that the FNP method together with optimal choice of an amphiphilic copolymer is a universal method to systematically control the aggregation state of AIE materials and hence tune the morphology and size of AIE nanoaggregates, which is potentially useful for precise imaging at specific tumor sites.

Near-Infrared Aggregation-Induced Emission-Active Probe Enables in situ and Long-Term Tracking of Endogenous β-Galactosidase Activity

“…In our strategy, QM is employed as the AIE building block along with generating modifiable sites for functionalization, which could perform controllable NIR emission via tuning electron–donor ability (Shi et al, 2013; Shao et al, 2014, 2015; Wang M. et al, 2018). Particularly, neighboring HBT moiety is covalent attached as hydrophobic π-conjugated backbone, efficiently extending emission wavelength to the NIR region.…”

“…Herein, we developed an elaborated NIR AIE-active β-gal probe for enabling in situ and long-term tracking of endogenous enzyme activity (Scheme 1). Firstly, we focus on our group-developed AIE building block of quinoline-malononitrile (QM) to overcome the enrichment quenching effect (Shi et al, 2013; Shao et al, 2014, 2015; Wang M. et al, 2018). Then, the lipophilic 2-(2-hydroxyphenyl) benzothiazole (HBT) moiety is covalently attached as an external π-conjugated backbone for extending the NIR emission.…”

High‐Performance Quinoline‐Malononitrile Core as a Building Block for the Diversity‐Oriented Synthesis of AIEgens

“…We further utilized the FNP method to regulate and control the size, shape, and orientation of AIE‐nanoparticles, and evaluated their rate, efficiency, and endocytic mechanism of the cellular uptake . We envisioned that the morphologies and sizes (nano‐sphere, nano‐rod, and micro‐rod) of AIE aggregates, and their sizes, ranging from one hundred nanometers to tens of micrometers, could be tuned by the nature and concentrations of the block copolymers.…”

“…The size and morphology (including bare nanoparticle, nanorod, microrod, and nanosphere) of ED particles can be tuned by the optimal polymer concentration and selection of the hydrophobic block. Intriguingly, as the aspect ratio is about 5, the nanorods show better cellular uptake and targeting capability in cancer cells, even better than nanospheres . More importantly, in a zebrafish model, the nanorod particles with polysaccharide (dextran) shell display excellent tumor‐targeting capability while the nanorod particles without such a polymer shell are randomly distributed (Figure b).…”

Nano-aggregates of furan-2-carbohydrazide derivatives displaying enhanced emission with a bathochromic shift

“…However, previous studies of the mechanism of the aggregation of molecules displaying ESIPT mainly focused on the p-p effect, which mainly blocks intramolecular rotational motion, but there have been few studies on the role of intramolecular H-bonding in the aggregation process. [21][22][23] In this work, we synthesized a new conjugated chromophore carrying a proton transfer segment, and this chromophore produced enol and keto double emission bands. The intensity of the keto emission became dramatically higher during aggregation of the chromophore, while the enol emission remained almost unchanged.…”