Theranostic lyotropic liquid crystalline nanostructures for selective breast cancer imaging and therapy.

Herein, we report the development of theranostic lyotropic liquid crystalline nanostructures (LCN's) loaded with unique MnO nanoparticles (MNPs) for selective cancer imaging and therapy. MNPs serves as a fluorescent agent as well as a source of manganese (Mn2+) and enables localized oxidative stress under the hallmarks of cancer (acidosis, high H2O2 level). In pursuit of synergistic amplification of Mn2+ antitumor activity, betulinic acid (BA) is loaded in LCN's. In this investigation, nano-architecture of LCN's phase interface is established via SAXS, Cryo-TEM and Cryo-FESEM. Intriguing in vitro studies showed that the LCN's triggered hydroxyl radical production and exhibited greater selective cytotoxicity in cancer cells, ensuring the safety of normal cells. Significant tumor ablation is realized by the 96.5 % of tumor growth inhibition index of LCN's as compared to control group. Key insights into on-site drug release, local anti-cancer response, and tumor location are gained through precise guidance of fluorescent MNPs. In addition, comprehensive assessment of the safety, pharmacokinetics and tumor distribution behavior of LCN's is performed in vivo or ex vivo. This work emphasizes the promise of modulating tumor microenvironment with smart endogenous stimuli sensitive nano systems to achieve advanced comprehensive cancer nano-theranostics without any external stimulus. STATEMENT OF SIGNIFICANCE: Effective diagnosis and treatment approaches with maximum anti-cancer activity and minimal side-effects are critical to ameliorate cancer therapy. Compared to radiation, photodynamic and photothermal therapy, the specific and selective activation of tumor microenvironmental endogenous stimuli for the logical generation of cytotoxic OH· free radicals serves as an efficient therapeutic strategy for chemodynamic-cancer treatment. In this investigation, MnO nanoparticles fulfill two needs (fluorescence-based optical imaging and a source of Mn2+ based chemodynamic therapy) in one unit. This approach also ensures the safety of normal cells, as the toxic OH· free radical activity is substantially suppressed under the mild alkaline/H2O2 conditions in normal cell microenvironment.

Self-assembled toron-like structures in inverse nematic gels.

A novel form of nematic gel (N-gel) wherein bright flower-like domains (BFDs) rich in gelator fibres are embedded in a matrix of liquid crystal (LC) molecules has been reported. These gels which we denote as inverse N-gels are unlike typical N-gels in which the LC is encapsulated within an aggregated network of gelator molecules. The self-organization of the helical gelator fibres within the BFDs leads to the creation of localized toron-like structures that are topologically protected due to their skyrmion director profile. Optical and confocal microscopy have been used to deduce the LC director configuration, in order to understand possible intermolecular interactions that can lead to the formation of the twisted structures and the inverse N-gels.

Clusters of B7 Fibers Reveal Origin of Blue Phase Stability in a Binary Mixture of Chiral Rod-like and Achiral Bent-Core Molecules.

Liquid crystal (LC) blue phases (BPs) have gained relevance because of their potential applicability as tunable photonic band gap materials. However, their narrow temperature range often restricts technical usage. Doping with an LC made of achiral bent-core (BC) molecules is one of the strategies employed to increase BP stability. It is now shown that mixing a BCLC exhibiting the polarization-modulated lamellar B7 phase, with a calamitic chiral LC made of rod-like (R) molecules, enhances the BP range considerably. The special feature in this system is the spontaneous expulsion of clusters of B7 fibers in the chiral nematic (N*) phase occurring below the BPs. This gives a clear indication that islands rich in BC molecules lie interspersed between the R molecules. Based on several experimental studies, it is shown that the BP stability may be attributed to an interplay of conformational and intrinsic chirality of the BC and R molecules across the interface of these islands. This study provides new insights from a molecular point of view and provides a novel technique for designing stable-induced BPs. The additional novelty is the occurrence of a phase transition within the fibers. Further, the electro-responsive fibers may also have a potential to form new materials.

Anisamide-Anchored Lyotropic Nano-Liquid Crystalline Particles with AIE Effect: A Smart Optical Beacon for Tumor Imaging and Therapy.

The prospective design of nanocarriers for personalized oncotherapy should be an ensemble of targeting, imaging, and noninvasive therapeutic capabilities. Herein, we report the development of the inverse hexagonal nano-liquid crystalline (NLC) particles that are able to host formononetin (FMN), a phytoestrogen with known anticancer activity, and tetraphenylethene (TPE), an iconic optical beacon with aggregation-induced emission (AIE) signature, simultaneously. Ordered three-dimensional mesoporous internal structure and high-lipid-volume fraction of NLC nanoparticles (NLC NPs) frame the outer compartment for the better settlement of payloads. Embellishment of these nanoparticles by anisamide (AA), a novel sigma receptor targeting ligand using carbodiimide coupling chemistry ensured NLC's as an outstanding vehicle for possible utility in surveillance of tumor location as well as the FMN delivery through active AIE imaging. The size and structural integrity of nanoparticles were evaluated by quasi-elastic light scattering, cryo field emission scanning electron microscopy small-angle X-ray scattering. The existence of AIE effect in the nanoparticles was evidenced through the photophysical studies that advocate the application of NLC NPs in fluorescence-based bioimaging. Moreover, confocal microscopy illustrated the single living cell imaging ability endowed by the NLC NPs. In vitro and in vivo studies supported the enhanced efficacy of targeted nanoparticles (AA-NLC-TF) in comparison to nontargeted nanoparticles (NLC-TF) and free drug. Apparently, this critically designed multimodal NLC NPs may establish a promising platform for targeted and image-guided chemotherapy for breast cancer.

Possible influence of layer deformation and chiral segregation on dielectric modes in the dark conglomerate liquid crystal.

Dielectric spectroscopy is used to investigate the structure, molecular dynamics, and relaxation phenomena in electric-field-induced switchable dark conglomerate (DC) phases in a bent-core liquid crystal. The DC phases are obtained by applying a high-frequency ac electric field in the B1rev phase or by cooling under a dc or an ac field from the isotropic phase. Although the DC phases exhibit good electro-optic switching properties, the dielectric parameters are different from those observed in typical lamellar SmCP phases and similar to those obtained in a non-switchable DC phase. We therefore propose that the dielectric response and reduced intensity of the relaxation modes may be a general feature in DC phases and may owe its origin to the deformed layer structure in which certain molecular motions are impeded. Further, we find that in the field-induced DC phases derived from the isotropic phase, the dielectric modes are affected by chiral segregation promoted by the applied field.