Far-Red and Near-IR AIE-Active Fluorescent Organic Nanoprobes with Enhanced Tumor-Targeting Efficacy: Shape-Specific Effects

We investigated the mechanism by which transferrin-coated gold nanoparticles (Au NP) of different sizes and shapes entered mammalian cells. We determined that transferrin-coated Au NP entered the cells via clathrin-mediated endocytosis pathway. The NPs exocytosed out of the cells in a linear relationship to size. This was different than the relationship between uptake and size. Furthermore, we developed a mathematical equation to predict the relationship of size versus exocytosis for different cell lines. These studies will provide guidelines for developing NPs for imaging and drug delivery applications, which will require "controlling" NP accumulation rate. These studies will also have implications in determining nanotoxicity.

Optically active nanomaterials promise to advance a range of biophotonic techniques through nanoscale optical effects and integration of multiple imaging and therapeutic modalities. Here, we report the development of porphysomes; nanovesicles formed from self-assembled porphyrin bilayers that generated large, tunable extinction coefficients, structure-dependent fluorescence self-quenching and unique photothermal and photoacoustic properties. Porphysomes enabled the sensitive visualization of lymphatic systems using photoacoustic tomography. Near-infrared fluorescence generation could be restored on dissociation, creating opportunities for low-background fluorescence imaging. As a result of their organic nature, porphysomes were enzymatically biodegradable and induced minimal acute toxicity in mice with intravenous doses of 1,000 mg kg(-1). In a similar manner to liposomes, the large aqueous core of porphysomes could be passively or actively loaded. Following systemic administration, porphysomes accumulated in tumours of xenograft-bearing mice and laser irradiation induced photothermal tumour ablation. The optical properties and biocompatibility of porphysomes demonstrate the multimodal potential of organic nanoparticles for biophotonic imaging and therapy.

A new class of organic nanoparticles (CN-MBE nanoparticles) with a mean diameter of ca. 30-40 nm, which exhibit a strongly enhanced fluorescence emission, were prepared by a simple reprecipitation method. CN-MBE (1-cyano-trans-1,2-bis-(4'-methylbiphenyl)ethylene) is very weakly fluorescent in solution, but the intensity is increased by almost 700 times in the nanoparticles. Enhanced emission in CN-MBE nanoparticles is attributed to the synergetic effect of intramolecular planarization and J-type aggregate formation (restricted excimer formation) in nanopaticles. On/off fluorescence switching for organic vapor was demonstrated with CN-MBE nanoparticles.