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Designing programmable biomaterials that could act as extracellular matrices and permit functionalization is a current need for tissue engineering advancement. DNA based hydrogels are gaining significant attention owing to their self-assembling properties, biocompatibility, chemical robustness and low batch to batch variability. The real potential of DNA hydrogels in the biomedical domain remains to be explored. In this work, a DNA hydrogel was coated on a glass surface and coupled to a synthetic IKVAV peptide by a chemical crosslinker. We observe enhanced neuronal differentiation, prolonged neurite length, dynamic movement of microtubules and cytoskeleton, and altered endocytic mechanisms in neuroblastoma-based stem cells for the peptide modified DNA hydrogel compared to the unmodified DNA hydrogel and controls. We anticipate that a peptide-modified DNA hydrogel could emerge as a promising scaffold coating material to develop nerve tissue conduits in the future for application in neuroscience and neuroregeneration.

We report the synthesis and characterization of the structures formed by self-assembly of 4-chloro-2(3H)-benzothiazolone (CBT) into panchromatic fibres and their application in cellular imaging. The aggregation properties of the synthesized compound were studied extensively under different solvents and concentrations and their morphologies examined at a supramolecular level by various microscopic techniques such as atomic force microscopy (AFM), fluorescence microscopy, and optical microscopy. Interestingly, the self-assembled structures formed by CBT reveal panchromatic emission properties and show blue, green, and red fluorescence under different excitation wavelengths. The mechanism of structure formation of the self-assemblies was studied through different techniques such as concentration-dependent 1H-NMR, ATR-FTIR, UV-visible spectroscopy, and fluorescence spectroscopy. Finally, the utility of CBT for cell imaging applications was demonstrated and it can be noted that CBT was efficiently taken up by mammalian cells and the cells revealed panchromatic emission in the blue, green, and red channels. The intensities of the fluorescence observed were blue > green > red and the dye interestingly does not exhibit any fluorescence quenching.

DNA-based nanotechnology has evolved into an autonomous, highly innovative, and dynamic field of research at the nexus of supramolecular chemistry, nanotechnology, materials science, and biotechnology. DNA-based materials, including origami nanodevices, have started to emerge as an ideal scaffold for use in cellular programming, tissue engineering, and drug delivery applications. We cover herein the applications for DNA as a scaffold for interfacing with, and guiding, the activity of biological systems like cells and tissues. Although DNA is a highly programmable molecular building block, it suffers from a lack of functional capacity for guiding and modulating cells. Coupling DNA to biologically active molecules can bestow bioactivity to these nanodevices. The main goal of such nanodevices is to synthesize systems that can bind to cells and mimic the extracellular environment, and serve as a highly promising toolbox for multiple applications in cellular programming and tissue engineering. DNA-based programmable devices offer a highly promising approach for programming collections of cells, tissue engineering, and regenerative medicine applications.

Localized cancer chemotherapy through injectable hydrogels is a next-generation advanced substitute for the currently operational systemic route of drug administration. Recently, several hydrogels have been developed for prospective drug delivery applications; however, no

Silk, a natural biopolymer, has been used clinically as suture material over thousands of years and has received much impetus for a plethora of biomedical applications in the last two decades. Silk protein isolated from both mulberry and nonmulberry silkworm varieties gained recognition as a potential biomaterial owing to its affordability and remarkable physicochemical properties. Molecular studies on the amino acid composition and conformation of silk proteins interpreted in the present review provide a critical understanding of the difference in crystallinity, hydrophobicity, and tensile strength among silkworm silk proteins. Meticulous silk fibroin (SF) isolation procedures and innovative processing techniques to fabricate gamut of two-dimensional (2D) and three-dimensional (3D) matrices including the latest 3D printed scaffolds have led SF for diverse biomedical applications. Crucial factors for clinical success of any biomaterial, including biocompatibility, immune response, and biodegradability, are discussed with particular emphasis on the lesser-known endemic nonmulberry silk varieties, which in recent years have gained considerable attention. The tunable biodegradation and bioresorbable attributes of SF enabled its use in drug delivery systems, thus proving it as an efficient and specific vehicle for controlled drug release and targeted drug delivery. Advancements in fabrication methodologies inspired biomedical researchers to develop SF-based

DNA has emerged as one of the smartest biopolymers to bridge the gap between chemical science and biology to design scaffolds like hydrogels by physical entanglement or chemical bonding with remarkable properties. We present here a completely new application of DNA-based hydrogels in terms of their capacity to stimulate membrane endocytosis, leading to enhanced cell spreading and invasion for cells in ex vivo 3D spheroids models. Multiscale simulation studies along with DLS data showed that the hydrogel formation was enhanced at lower temperature and it converts to liquid with increase in temperature. DNA hydrogels induced cell spreading as observed by the increase in cellular area by almost two-fold followed by an increase in the receptor expression, the endocytosis, and the 3D invasion potential of migrating cells. Our first results lay the foundation for upcoming diverse applications of hydrogels to probe and program various cellular and physiological processes that can have lasting applications in stem cell programming and regenerative therapeutics.

The major limitations of traditional methods of anticancer drug delivery include systemic distribution and frequent administration intravenously. To address these issues, in our present approach, we have fabricated a nano hybrid silk hydrogel system for localized, targeted, and on-demand delivery of anticancer drugs. The hybrid system contains a blend of two varieties of silk protein and doxorubicin (DOX)-loaded folic acid functionalized single-walled carbon nanotubes (SWCNT-FA/DOX). Owing to the single-walled carbon nanotube (SWCNT) incorporation, the mechanical strength of the hybrid silk hydrogel composite enhanced significantly. A slow and sustained DOX release was recorded over a 14 day study. The amount of DOX released was determined by concentration of the SWCNT-FA/DOX payload, rate of silk degradation, pH of the released medium, and incubation temperature. The intermittent exposure of near-infrared light to the hybrid gel system stimulated on-demand DOX release. The

DNA has emerged as one of the smartest biopolymers to bridge the gap between chemical science and biology to design scaffolds like hydrogels by physical entanglement or chemical bonding with remarkable properties. We present here a completely new application of DNA based hydrogels in terms of their capacity to stimulate membrane endocytosis, leading to enhanced cell spreading and invasion for cells in ex-vivo 3D spheroids models. Multiscale simulation studies along with DLS data showed that the hydrogel formation was enhanced at lower temperature and it converts to liquid with increase in temperature. DNA hydrogels induced cell spreading as observed by increase in cellular area by almost two-folds followed by increase in receptor expression, endocytosis and 3D invasion potential of migrating cells. Our first results lay the foundation for upcoming diverse applications of hydrogels to probe and program various cellular and physiological processes that can have lasting applications in stem cells programming and regenerative therapeutics.

We report for the very first time self-assembly of a red color dye 7-Amino-6h-anthra[9,1-cd][1,2]thiazol-6-one (AAT),its photophysical properties and its applications in cell imaging.Interestingly, AAT show intense red colour in visible light while it shows the orange colour fluorescence under UV light @312nm.Surprisingly, when this dye was used as cell imaging agent it revealed only green fluorescence inside cells and not red. Hence, the photophysical properties of this dye was very intriguing. Further, when self-assembling properties of this dye was examined it revealed formation of tree like branched structures which appeared red both under green and red filter which was again an unexpected result..Interestingly AAT self-assembly also show morphological transition and the branched tree like structures changes to straight fibres as the solvent is changed from DMSO to THF. Hence, the results of self-assembly and cell imaging were contrary to each other and the photophysical properties of this dye is very unusual as compared to conventional dyes. Our future endeavours willaim to understand this anomalous behaviour in greater details in future through various biophysical assays.

We report for the very first-time self-assembly of 4-(5-methoxythiazolo[4,5-b]pyridin-2-yl)-N,N-dimethylaniline (TPA) to fluorescent sunflower-like architectures. Interestingly, TPA exhibits blue fluorescence in visible light at 385 nm and the fluorescence is not affected by photo-induced quenching rather the fluorescence keeps on increasing with time under broad day light. The morphologies of self-assembled structures of TPA were studied at various concentrations in dimethyl sulphoxide (DMSO) and Tetrahydrofuran (THF). The microscopic studies through SEM and fluorescence microscopy reveal the formation of sunflower-like fluorescent self-assemblies. Further, our study revealed that the sunflower shaped assemblies formed by TPA exhibitfluorescence under blue, green, and red channels that can be evinced by the fluorescence spectroscopy and microscopy. Hence TPA exhibits panchromatic emission properties and it reveals tunable emission properties under different excitation wavelengths. Further, AIE properties of TPA were evinced by recording fluorescence in THF under varying concentrations of water and doing solvent chromic studies.Finally,the utility of TPA as a cell imaging agent was studied in human breast cancer cell lines (MDA-MB-231) which suggested TPA can penetrate the cell membrane and can be effectively used as a cell labeling dye.

We report the synthesis and characterization of self-assembled structures formed by4-Choro-2(3H)-benzothiazolone (VK) to panchromatic fibers and its application as cell imaging tool. The aggregation properties ofthe synthesized compounds have been studied extensively under different solvent and concentrationand theirmorphologies examined at supramolecular level was observed by microscopic techniques like optical microscopy, fluorescence microscopy, and atomic force microscopy(AFM). Interestingly, the self-assembled structures formed by VKreveal panchromatic emission properties andshow blue, green and red fluorescence under different excitation filters. The intensity of the fluorescence observed was blue>green>red and the dye interestingly do not show any fluorescence quenching, on the other hand reveal photoactive properties under green channel. The mechanisms of formation of the self-assemblies were studied through different techniques like concentration dependent NMR and,UV visible spectroscopy and fluorescencemicroscopic studies.Finally, the utility of VK for cell imaging applications is demonstrated and it can be noted that VK can be efficientlyup taken by mammalian cells and the stained cells reveal panchromatic emission under blue, green and red channel.

Conventional systemic chemotherapeutic regimens suffer from challenges such as nonspecificity, shorter half-life, clearance of drugs, and dose-limiting toxicity. Localized delivery of chemotherapeutic drugs through noninvasive spatiotemporally controllable stimuli-responsive drug delivery systems could overcome these drawbacks while utilizing drugs approved for cancer treatment. In this regard, we developed photoelectro active nanocomposite silk-based drug delivery systems (DDS) exhibiting on-demand drug release in vivo. A functionally modified single-walled carbon nanotube loaded with doxorubicin (DOX) was embedded within a cross-linker free silk hydrogel. The resultant nanocomposite silk hydrogel showed electrical field responsiveness and near-infrared (NIR) laser-induced hyperthermal effect. The remote application of these stimuli in tandem or independent manner led to the increased thermal and electrical conductivity of nanocomposite hydrogel, which effectively triggered the intermittent on-demand drug release. In a proof-of-concept in vivo tumor regression study, the nanocomposite hydrogel was administered in a minimally invasive way at the periphery of the tumor by covering most of it. During the 21-day study, drastic tumor regression was recorded upon regular stimulation of nanocomposite hydrogel with simultaneous or individual external application of an electric field and NIR laser. Tumor cell death marker expression analysis uncovered the induction of apoptosis in tumor cells leading to its shrinkage. Heart ultrasound and histology revealed no cardiotoxicity associated with localized DOX treatment. To our knowledge, this is also the first report to show the simultaneous application of electric field and NIR laser in vivo for localized tumor therapy, and our results suggested that such strategy might have high clinical translational potential.

Since their discovery, carbon nanotubes (CNTs) have been regarded as a fascinating feat of human contrivance. These lightweight materials feature a large aspect ratio and are bestowed with incredible mechanical properties, as well as high flexibility and high electrical conductivity, which have endeared them to be actively researched over the last decade in pertinence to high-end electrical and communication related applications. However, the use of CNTs in their bulk form results in a poor translation of their inherent properties, limiting technological advancement to macroscopic formats. To exploit their endogenous attributes, it becomes crucial to composite CNTs with engineering polymers (e.g., thermoplastics, elastomers, conjugated polymers) or natural polymers to obtain nanocomposites with augmented benefits. In this chapter, we present the different strategies adopted for surface modifications of CNTs, which are necessary for their efficient interactions with any polymer of interest. Also, insights into different strategies opted for the fabrication of nanocomposite matrices to achieve intercalative and exfoliative structures are also presented. The physical properties of thus fabricated polymer/CNT nanocomposites are also discussed with emphasis on their mechanical, thermal, electrical, rheological, and optical attributes. The chapter also focuses on a few recent advanced applications of these nanocomposites in the domains of microelectronics, including efficient energy storage devices and health care applications with special impetus on targeted drug delivery systems and tissue engineering applications.

A unique irregular hexagon was self-assembled using an organic donor clip (bearing terminal pyridyl units) and a complementary organometallic acceptor clip. The resulting metallamacrocycle was characterized by multinuclear NMR, mass spectrometry, and elemental analyses. Molecular modeling confirmed hexagonal shaped cavity for this metallamacrocycle which is a unique example of a discrete hexagonal framework self-assembled from only two building blocks. Cytotoxicity of the Pt-based acceptor tecton and the self-assembled PtII-based macrocycle was evaluated using three cancer cell lines and results were compared with cisplatin. Results confirmed a positive effect of the metallamacrocycle formation on cell growth inhibition.

Two new irregular hexagons (6 and 7) were synthesized from a pyrazine motif containing an organometallic acceptor clip [bearing platinum(II) centers] and different neutral donor ligands (4,4'-bipyridine or pyrazine) using a coordination-driven self-assembly protocol. The two-dimensional supramolecules were characterized by multinuclear NMR, mass spectrometry, and elemental analyses. Additionally, one of the macrocycles (6) was characterized by single-crystal X-ray analyses. Macrocycles are unique examples of [2 + 2] self-assembled ensembles that are hexagonal but irregular in shape. These hexagon frameworks require the assembly of only four tectons/subunits. The cytotoxicity of platinum(II)-based macrocycles was studied using various cell lines such as A549 (human lung carcinoma), KB (human oral cancer), MCF7 (human breast cancer), and HaCaT (human skin keratinocyte) cell lines, and the results were compared with those of cisplatin. The smaller macrocycle (7) exhibited a higher cytotoxic effect against all cell types, and its sensitivity was found to be comparable with that of cisplatin for A549 and MCF7 cells. Cell cycle analysis and live propidium iodide staining suggest that the macrocycles 6 and 7 induced a loss of membrane integrity that ultimately might lead to necrotic cell death.