Cubosome nanoparticles for enhanced delivery of mitochondria anticancer drug elesclomol and therapeutic monitoring via sub-cellular NAD(P) H multi-photon fluorescence lifetime imaging

Elesclomol (ELC) is an anticancer drug inducing mitochondria cytotoxicity through reactive oxygen species.Here,for the first time,we encapsulate the poorly water soluble ELC in monoolein-based cubosomes stabilized with Pluronic F127.Cellular uptake and nanocarrier accumulation close to the mitochondria with sub-micrometer distance is identified via three-dimensional (3D) confocal microscopy and edge-to-edge compartment analysis.To monitor the therapeutic effect of the ELC nanocarrier,we apply for the first time,label-free time-lapse multi-photon fluorescence lifetime imaging microscopy (MP-FLIM) to track NAD(P)H cofactors with sub-cellular resolution on live cells exposed to an anticancer nanocarrier.Improved in vitro cytotoxicity is verified when loading the pre-complexed ELC with copper (ELC-Cu).Importantly,for equivalent copper concentration,cubosomes loaded with ELC-Cu show higher cytotoxicity compared to the free drug.The novel nanocarrier shows promising features for systemic ELC-Cu administration,and furthermore we establish the MP-FLIM technique for the assessment of anticancer drug delivery systems.

Bound states in the continuum and Fano resonances in the strong mode coupling regime

The study of resonant dielectric nanostructures with a high refractive index is a new research direction in the nanoscale optics and metamaterial-inspired nanophotonics.Because of the unique optically induced electric and magnetic Mie resonances,high-index nanoscale structures are expected to complement or even replace different plasmonic components in a range of potential applications.We study a strong coupling between modes of a single subwavelength high-index dielectric resonator and analyze the mode transformation and Fano resonances when the resonator’s aspect ratio varies.We demonstrate that strong mode coupling results in resonances with high-quality factors,which are related to the physics of bound states in the continuum when the radiative losses are almost suppressed due to the Friedrich–Wintgen scenario of destructive interference.We explain the physics of these states in terms of multipole decomposition,and show that their appearance is accompanied by a drastic change in the far-field radiation pattern.We reveal a fundamental link between the formation of the high-quality resonances and peculiarities of the Fano parameter in the scattering cross-section spectra.Our theoretical findings are confirmed by microwave experiments for the scattering of high-index cylindrical resonators with a tunable aspect ratio.The proposed mechanism of the strong mode coupling in single subwavelength high-index resonators accompanied by resonances with high-quality factors helps to extend substantially functionalities of all-dielectric nanophotonics,which opens horizons for active and passive nanoscale metadevices.

Plasmon-assisted optical trapping and anti-trapping

The ability to manipulate small objects with focused laser beams has opened a venue for investigating dynamical phenomena relevant to both fundamental and applied science.Nanophotonic and plasmonic structures enable superior performance in optical trapping via highly confined near-fields.In this case,the interplay between the excitation field,re-scattered fields and the eigenmodes of a structure can lead to remarkable effects;one such effect,as reported here,is particle trapping by laser light in a vicinity of metal surface.Surface plasmon excitation at the metal substrate plays a key role in tailoring the optical forces acting on a nearby particle.Depending on whether the illuminating Gaussian beam is focused above or below the metal-dielectric interface,an order-of-magnitude enhancement or reduction of the trap stiffness is achieved compared with that of standard glass substrates.Furthermore,a novel plasmon-assisted anti-trapping effect(particle repulsion from the beam axis)is predicted and studied.A highly accurate particle sorting scheme based on the new anti-trapping effect is analyzed.The ability to distinguish and configure various electromagnetic channels through the developed analytical theory provides guidelines for designing auxiliary nanostructures and achieving ultimate control over mechanical motion at the microand nano-scales.