Photoswitchable Nanoparticles Research Articles

Reversible Light-Triggered Stretching of Small-Molecule Photochromic Organic Nanoparticles.

Functional organic nanomaterials are nowadays largely spread in the field of nanomedicine. In situ modulation of their morphology is thus expected to considerably impact their interactions with the surroundings. In this context, photoswitchable nanoparticles that are manufactured, amenable to extensive disassembling upon illumination in the visible, and reversible reshaping under UV exposure. Such reversibility turns to be strongly impaired for photochromic nanoparticles in close contact with a substrate. In situ atomic force microscopy investigations at the nanoscale actually reveal progressive disintegration of the organic nanoparticles under successive UV-vis cycles of irradiation, in the absence of intrinsic elastic forces. These results point out the dramatic interactions exerted by surfaces on the cohesion of non-covalently bonded organic nanoparticles. They invite to harness such systems, often used as biomarkers, to also serve as photoactivatable drug delivery nanocarriers.

Interaction of photoswitchable nanoparticles with cellulosic materials for anticounterfeiting and authentication security documents

Invisible high-security anticounterfeiting inks were developed by surface-modification of functionalized latex nanoparticles with spiropyran derivatives, which display both photochromism and fluorescence upon UV irradiation at the same time. The functionalized latex nanoparticles show different spherical, doughnut-like, and red blood cell-like morphologies depending on concentration and type of its functional groups. Microscopic investigation of the impregnated cellulosic papers with latex nanoparticles display that epoxy-functionalized spherical latex nanoparticles have considerable packing and stability on the surface of the cellulosic substrate by formation of hydrogen bonding. Epoxy-functionalized latex nanoparticles containing spiropyran were used for preparation of high-security photochromic/fluorescent anticounterfeiting inks for print-marking of different cellulosic security documents such as certificate, money, and passport with different marks. The printed marks and finger-prints on the cellulosic security documents display photochromism and red fluorescence emission upon UV irradiation with high intensity and brightness.

Live Cell Imaging Using Photoswitchable Diarylethene-Doped Fluorescent Polymer Dots.

Fluorescence photoswitching using nanomaterials has recently emerged as a promising approach for the imaging of biological targets. However, despite intensive research efforts during the last decade, practical microscopy of biological targets using photoswitchable nanoparticles in real time remains challenging. To address this problem, we have developed live macrophage cell imaging and single particle imaging methods, using photoswitchable fluorescent diarylethene-doped polymer nanoparticles (P-dots) under Xe lamp irradiation. We established a 34-times prolonged "off-state", using P-dots doped with a diarylethene-containing methoxy substituent, upon visible-light irradiation using a Xe lamp and a green fluorescent protein filter cube. To demonstrate the practicality of doped P-dots imaging, we imaged lysosomes in macrophage cells, and observed 11-times slower recovery of the fluorescence from the "off-state" to the "on-state", indicating their potential for cellular imaging.

The carbon nanoparticles grafted with copolymers of styrene and spiropyran with reversibly photoswitchable fluorescence

A kind of photoswitchable nanoparticles which are the fluorescent carbon nanoparticles grafted with the copolymers of styrene and spiropyran (f-CNP-g-poly(St-co-SP) is reported. The f-CNP-g-poly(St-co-SP) not only feature the reversibly photoswitchable fluorescence, but also have good processability. Their fluorescence could be reversibly switched between blue-green and red by using ultraviolet/visible light irradiation. Furthermore, they could be readily processed into nanofibers with reversibly photoswitchable fluorescence by electrospinning. They can be potentially applied in fabricating microdevice, optical switching, information storage, anti-counterfeiting as well as biological imaging.

Photoswitchable fluorescent nanoparticles and their emerging applications

Although fluorescence offers ultrasensitivity, real-world applications of fluorescence techniques encounter many practical problems. As a noninvasive means to investigate biomolecular mechanisms, pathways, and regulations in living cells, the intrinsic heterogeneity and inherent complexity of biological samples always generates optical interferences such as autofluorescence. Therefore, innovative fluorescence technologies are needed to enhance measurement reliability while not compromising sensitivity. In this review, we present current strategies that use photoswitchable nanoparticles to address these real-world challenges. The unique feature in these photoswitchable nanoparticles is that fundamental molecular photoswitches are playing the critical role of fluorescence modulation rather than traditional methods like modulating the light source. As a result, new innovative technologies that have recently emerged include super-resolution imaging, frequency-domain imaging, antiphase dual-color correlation, etc. Some of these methods improve imaging resolution down to the nanometer level, while others boost the detection sensitivity by orders of magnitude and confirm the nanoparticle probes unambiguously. These enhancements, which are not possible with non-photoswitching molecular probes, are the central topics of this review.

Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo.

Despite progress in detecting circulating tumor cells (CTCs), existing assays still have low sensitivity (1–10 CTC/mL) due to the small volume of blood samples (5–10 mL). Consequently, they can miss up to 103–104 CTCs, resulting in the development of barely treatable metastasis. Here we analyze a new concept of in vivo CTC detection with enhanced sensitivity (up to 102–103 times) by the examination of the entire blood volume in vivo (5 L in adults). We focus on in vivo photoacoustic (PA) flow cytometry (PAFC) of CTCs using label-free or targeted detection, photoswitchable nanoparticles with ultrasharp PA resonances, magnetic trapping with fiber-magnetic-PA probes, optical clearance, real-time spectral identification, nonlinear signal amplification, and the integration with PAFC in vitro. We demonstrate PAFC’s capability to detect rare leukemia, squamous carcinoma, melanoma, and bulk and stem breast CTCs and its clusters in preclinical animal models in blood, lymph, bone, and cerebrospinal fluid, as well as the release of CTCs from primary tumors triggered by palpation, biopsy or surgery, increasing the risk of metastasis. CTC lifetime as a balance between intravasation and extravasation rates was in the range of 0.5–4 h depending on a CTC metastatic potential. We introduced theranostics of CTCs as an integration of nanobubble-enhanced PA diagnosis, photothermal therapy, and feedback through CTC counting. In vivo data were verified with in vitro PAFC demonstrating a higher sensitivity (1 CTC/40 mL) and throughput (up to 10 mL/min) than conventional assays. Further developments include detection of circulating cancer-associated microparticles, and super-resolution PAFC beyond the diffraction and spectral limits.

Dynamic self-assembly of photo-switchable nanoparticles

Nanoparticles functionalized with photo-switchable ligands can be assembled into a broad range of structures by controlled light exposure. In particular, alternating light exposures provide the means to control formation of assemblies of various sizes and symmetries. Here, we use scaling arguments and Kinetic Monte Carlo simulations to study the evolution of reversible aggregates in a solution of periodically irradiated photo-switchable nanoparticles. Scaling estimates of the characteristic size and the mean separation of aggregates agree with the simulations. The transition probabilities in the Kinetic Monte Carlo scheme are derived from a renormalized master equation of the diffusion process. Simulations on a system of nanoparticles, interacting through Lennard-Jones pair potentials that change their character from repulsive to attractive depending on the light exposure, show that the slow diffusion of particles at low effective temperatures (where the attractions are much higher than the thermal energy) results in the formation of small, “kinetically frozen” aggregates. On the other hand, aggregation does not occur at high effective temperatures, where the attractions are comparable to the thermal energy. In the intermediate range of effective temperatures, “fluctuating” aggregates form that can be stabilized by applying light pulses of specific lengths and frequencies. The aggregate sizes increase by increasing the packing fraction and the aggregates undergo transition to a percolated “network” at high packing fractions. Light-control of inter-particle interactions can either inhibit or promote nucleation and growth, and can reduce gel and glass formation.

Photoswitchable Nanoparticles Enable High-Resolution Cell Imaging: PULSAR Microscopy

Beyond-diffraction-limit optical imaging of cells will reveal biological mechanisms, cellular structures, and physiological processes in nanometer scale. Harnessing the photoswitching properties of spiropyran fluorophores, we achieved nanoresolution fluorescence imaging using photoactuated unimolecular logical switching attained reconstruction (PULSAR) microscopy. The PULSAR microscope successfully resolved nanostructures and subcellular organelles when the photoswitchable nanoparticles containing spiropyran dyes were used as fluorescent probes.