Background: Spatiotemporal regulation is one of the major considerations for developing a controlled and targeted drug delivery system to treat diseases efficiently. Light-responsive plasmonic nanostructures take advantage due to their tunable optical and photothermal properties by changing size, shape, and spatial arrangement. Results: In this study, self-integrated plasmonic hybrid nanogels (PHNs) are developed for spatiotemporally controllable drug delivery through light-driven conformational change and photothermally-boosted endosomal escape. PHNs are easily synthesized through the simultaneous integration of gold nanoparticles (GNPs), thermo-responsive poly (N-isopropyl acrylamide), and linker molecules during polymerization. Wave-optic simulations reveal that the size of the PHNs and the density of the integrated GNPs are crucial factors in modulating photothermal conversion. Several linkers with varying molecular weights are inserted for the optimal PHNs, and the alginate-linked PHN (A-PHN) achieves more than twofold enhanced heat conversion compared with others. Since light-mediated conformational changes occur transiently, drug delivery is achieved in a spatiotemporally controlled manner. Furthermore, light-induced heat generation from cellular internalized A-PHNs enables pinpoint cytosolic delivery through the endosomal rupture. Finally, the deeper penetration for the enhanced delivery efficiency by A-PHNs is validated using multicellular spheroid. Conclusion: This study offers a strategy for synthesizing light-responsive nanocarriers and an in-depth understanding of light-modulated site-specific drug delivery. Graphical

Histones are closely related to the state of chromatin, and epigenetic modification of their tail results in regulation in cells. Therefore, developing various analytical tools to map the changes in position and distribution of histone modifications is helpful in studying underlying mechanisms. Herein, we propose a high-spatial and colourimetric imaging method using plasmonic nanoparticles as probes to visualize heterochromatin histone markers in a single nucleus. We visualized the reorganization between repressive histone markers, H3K9me3 and H3K27me3, caused by oncogene-induced senescence based on the scattering colours and spectral shift of plasmonic nanoprobes to longer wavelengths using their distance-dependent coupling effect. The measured scattering profiles were correlated with the computation results simulating the scattering spectra according to the arrangements and distances among the plasmonic nanoprobes. The plasmonic nanoprobe-based high-spatial hyperspectral imaging provides an advanced way to study the dynamics of histone modifications for predicting the progression of diseases or senescence.

Chemotherapy is an important method in the field of cancer treatment and often follows surgery and/or radiotherapy to remove as many tumor cells as possible. In particular, among the chemotherapy methods, treatment using electromagnetic-based actuation systems is considered an effective method owing to the remote control of nanorobots. The existing electromagnetic-based actuation systems, however, have certain disadvantages such as the lack of degrees of freedom and the difficulty of manipulating large numbers of nanorobots (i.e., nanorobot clusters). Herein, we report that nanorobot clusters can be manipulated with high degrees of freedom through a simple parameter alpha that easily controls the gradient of the magnetic field of a multi-coil electromagnetic actuation system. The simulation results show that the gradient of the magnetic field is controlled using an introduced parameter, alpha, and the corresponding velocity is also controlled. Not only the velocity of the nanorobot cluster but also the unrestricted spatial control is enabled in two- and three-dimensions. We believe this study highlights an efficient method of electromagnetic control for cluster-based drug delivery.

Reactive oxygen species (ROS) regulate various physiological and pathological conditions in cells by interacting with signaling molecules and inducing oxidative stress. Therefore, sensitive monitoring of ROS levels in living cells is important to track cellular state and study the complex role of ROS in the development of various pathologies. Herein, we present an optically tunable plasmonic interface covered with graphene to monitor cellular ROS levels with superior sensitivity and cellular comfortability. As a sensing principle, we employed plasmon resonance energy transfer (PRET)-based spectral quenching dips modulated by redox-active cytochrome c for real-time monitoring. By transferring graphene layers to plasmonic nanoparticles immobilized on a glass substrate, the scattering profiles of the nanoprobes were adjusted in terms of the position, width, and intensity of the peaks to determine the optimal conditions for measuring the PRET signal. Using the optimized graphene-covered plasmonic nanoprobe, we obtained calibration curves over a wide concentration range from femtomoles to millimoles for hydrogen peroxide based on the change in the PRET signal. Before monitoring cellular ROS, we confirmed that a high density of cells adhered well to the graphene-covered plasmonic interface by observing immunofluorescence images of the cytoskeleton of the immobilized cells. Finally, we monitored the real-time ROS generated by the cells under oxidative stress conditions by directly measuring the spectral changes of the probes around the cells. We believe that the proposed graphene-covered tunable plasmonic interface has versatile applicability for investigating cellular stress and disease progression by monitoring ROS levels under various cellular conditions.