Perylene Diimide Nanoprobes for In Vivo Tracking of Mesenchymal Stromal Cells Using Photoacoustic Imaging.

Noninvasive bioimaging techniques are critical for assessing the biodistribution of cellular therapies longitudinally. Among them, photoacoustic imaging (PAI) can generate high-resolution images with a tissue penetration depth of ∼4 cm. However, it is essential and still highly challenging to develop stable and efficient near-infrared (NIR) probes with low toxicity for PAI. We report here the preparation and use of perylene diimide derivative (PDI) with NIR absorbance (around 700 nm) as nanoprobes for tracking mesenchymal stromal cells (MSCs) in mice. Employing an in-house synthesized star hyperbranched polymer as a stabilizer is the key to the formation of stable PDI nanoparticles with low toxicity and high uptake by the MSCs. The PDI nanoparticles remain within the MSCs as demonstrated by in vitro and in vivo assessments. The PDI-labeled MSCs injected subcutaneously on the flanks of the mice are clearly visualized with PAI up to 11 days postadministration. Furthermore, bioluminescence imaging of PDI-labeled luciferase-expressing MSCs confirms that the administered cells remain viable for the duration of the experiment. These PDI nanoprobes thus have good potential for tracking administered cells in vivo using PAI.

Formation of hydrophobic drug nanoparticles via ambient solvent evaporation facilitated by branched diblock copolymers.

Hydrophobic drug nanoparticles have been prepared by ambient solvent evaporation from ethanol at room temperature. Poly(ethylene glycol)-b-(N-isopropylacrylamide) (PEG-b-PNIPAm) branched diblock copolymers are employed to prevent drug crystallization during solvent evaporation and to stabilize the drug nanoparticles once suspended in aqueous media. After the initial solvent evaporation the dry materials obtained exhibit excellent stability during storage and can be readily dissolved in water to produce aqueous drug nanoparticles suspensions. Among the hydrophobic compounds investigated, Ketoprofen nanoparticles (Dh≈200nm, stable up to 9 months in solution) can be produced with a drug suspension yield of 96% at a drug:polymer ratio of 0.33:1 or a drug suspension yield of 80% at a drug:polymer ratio of 1:1. UV-vis spectroscopy has been used to determine the yield of drug suspended in aqueous media while cryo-TEM, dynamic light scattering (DLS) and powder x-ray diffraction (PXRD) are used to characterize the drug nanoparticles prepared.

Unimolecular branched block copolymer nanoparticles in methanol for the preparation of poorly water-soluble drug nanoparticles.

Spherical unimolecular amphiphilic branched A-B block copolymer nanoparticles in methanol are fabricated via thermal annealing using the methanolic upper critical solution temperature (UCST) of the hydrophobic block segment. These polymer nanoparticles are then used to produce an aqueous poorly water-soluble drug nanoparticle suspension with a mass : drug ratio of 1 : 1 and 100% nanoparticle yield. The drug nanoparticles in the suspension are stabilized by multiple polymer nanoparticles.

Highly Stable and Conductive Microcapsules for Enhancement of Joule Heating Performance.

Nanocarbons show great promise for establishing the next generation of Joule heating systems, but suffer from the limited maximum temperature due to precociously convective heat dissipation from electrothermal system to surrounding environment. Here we introduce a strategy to eliminate such convective heat transfer by inserting highly stable and conductive microcapsules into the electrothermal structures. The microcapsule is composed of encapsulated long-chain alkanes and graphene oxide/carbon nanotube hybrids as core and shell material, respectively. Multiform carbon nanotubes in the microspheres stabilize the capsule shell to resist volume-change-induced rupture during repeated heating/cooling process, and meanwhile enhance the thermal conductance of encapsulated alkanes which facilitates an expeditious heat exchange. The resulting microcapsules can be homogeneously incorporated in the nanocarbon-based electrothermal structures. At a dopant of 5%, the working temperature can be enhanced by 30% even at a low voltage and moderate temperature, which indicates a great value in daily household applications. Therefore, the stable and conductive microcapsule may serve as a versatile and valuable dopant for varieties of heat generation systems.

Nanoformulation and encapsulation approaches for poorly water-soluble drug nanoparticles.

During the last few decades the nanomedicine sector has emerged as a feasible and effective solution to the problems faced by the high percentage of poorly water-soluble drugs. Decreasing the size of such drug compounds to the nanoscale can significantly change their physical properties, which lays the foundation for the use of nanomedicine for pharmaceutical applications. Various techniques have been developed to produce poorly water-soluble drug nanoparticles, mainly to address the poor water-soluble issues but also for the efficient and targeted delivery of such drugs. These techniques can be generally categorized into top-down, bottom-up and encapsulation approaches. Among them, the top-down approaches have been the main choice for industrial preparation of drug nanoparticles while other methods are actively investigated by researchers. In this review, we aim to give a comprehensive overview and latest progress of the top-down, bottom-up, and encapsulation methods for the preparation of poorly water-soluble drug nanoparticles and how solvents and additives can be selected for these methods. In addition to the more industrially applied top-down approaches, the review is focused more on bottom-up and encapsulation methods, particularly covering supercritical fluid-related methods, cryogenic techniques, and encapsulation with dendrimers and responsive block copolymers. Some of the approved and mostly used nanodrug formulations on the market are also covered to demonstrate the applications of poorly water-soluble drug nanoparticles. This review is complete with perspectives on the development and challenges of fabrication techniques for more effective nanomedicine.

Drug nanoparticles by emulsion-freeze-drying via the employment of branched block copolymer nanoparticles.

A large percentage of drug compounds exhibit low water solubility and hence low bioavailability and therapeutic efficacy. This may be addressed by preparation of drug nanoparticles, leading to enhanced dissolution rate and direct use for treatment. Various methods have been developed to produce drug nanocrystals, including wet milling, homogenization, solution precipitation, emulsion diffusion, and the recently developed emulsion freeze-drying. The drawback for these methods may include difficult control in particles size, use of surfactants & polymer, and low ratio of drug to stabilizer. Here, biocompatible branched block copolymer nanoparticles with lightly-crosslinked hydrophobic core and hydrophilic surface groups are synthesized by the direct monomer-to-particle methodology, characterized, and then used as scaffold polymer/surfactant to produce drug nanoparticles via the emulsion-freeze-drying approach. This method can be used for model organic dye and different poorly water-soluble drugs. Aqueous drug nanoparticle dispersions can be obtained with high ratio of drug to stabilizer and relatively uniform nanoparticle sizes.