Reji Varghese

There has always been a growing demand for the development of advanced materials with dynamic properties for multi‐level data encryption and anticounterfeiting. Herein, we report a facile one‐pot, aqueous synthesis of a high nuclearity, luminescent, and circularly polarised luminescence (CPL)‐active terbium‐threonine supramolecular chiral emitters ( Tb‐Thr _D/L ‐G NCs) from readily available precursors. An aqueous solution of Tb‐Thr _D/L ‐G NCs exhibits (i) 100% transparency, (ii) tunable luminescence and CPL, and (iii) pH feedback loop‐controlled “on‐off” of luminescence and CPL. By exploring these features, multi‐level data encryption with enhanced security is demonstrated. The remarkable features of our strategy include: (i) temporal control over encryption‐decryption, (ii) ability to expunge the stored information autonomously, and (iii) four distinct keys to decrypt the information, thereby offering enhanced security for the stored data. The potential of NCs as a covert anticounterfeiting ink for inkjet printing, and their excellent compatibility with commercially available polymer matrices such as polyvinyl alcohol, are also demonstrated. We believe that our rational strategy for the scalable synthesis of Tb‐Thr _D/L ‐G NCs with remarkable optical and chiroptical properties in aqueous media using readily available materials will pave the way for the facile synthesis of new lanthanide‐based chiral emitters with promising applications.

Achieving long‐range 1D organization of semiconductor nanocrystals without altering their inherent optical properties is highly challenging, yet crucial for their applications. Herein, we report on the secondary‐nucleation‐triggered supramolecular polymerization of an alkyl chain‐tethered tetraphenylethylene derivative ( TPE‐A ) in dodecane, leading to the formation of ultralong, rigid, bundled and straight 1D fibers. Supramolecular polymerization of TPE‐A in dodecane proceeds through a nucleation–elongation mechanism, resulting in non‐emissive 1D nanofibers as the primary kinetic aggregates ( Aggr _KP ). The non‐emissive characteristic of Aggr _KP suggests that the tetraphenylethylene (TPE) units within Aggr _KP are in a “monomer‐like” state. The TPE units and alkyl chains in Aggr _KP enable their interaction with free monomers in solution, thereby acting as “seed” for catalyzing secondary nucleation. This process leads to the temporal evolution of highly fluorescent, ultralong, rigid bundled fibers as the stable thermodynamic product ( Aggr _TP ). The enhanced fluorescence of Aggr _TP is attributed to the aggregation‐induced emission from the TPE during the bundling of the nanofibers. As a result of secondary‐nucleation‐triggered bundling, Aggr _TP creates multiple micrometer‐long, straight, parallel, 1D hydrophobic lanes. The potential of the hydrophobic lanes in Aggr _TP to serve as a supramolecular template for the long‐range 1D organization of semiconductor nanocrystals without compromising their inherent optical properties is demonstrated.

Achieving long‐range 1D organization of semiconductor nanocrystals without altering their inherent optical properties is highly challenging, yet crucial for their applications. Herein, we report on the secondary‐nucleation‐triggered supramolecular polymerization of an alkyl chain‐tethered tetraphenylethylene derivative ( TPE‐A ) in dodecane, leading to the formation of ultralong, rigid, bundled and straight 1D fibers. Supramolecular polymerization of TPE‐A in dodecane proceeds through a nucleation–elongation mechanism, resulting in non‐emissive 1D nanofibers as the primary kinetic aggregates ( Aggr _KP ). The non‐emissive characteristic of Aggr _KP suggests that the tetraphenylethylene (TPE) units within Aggr _KP are in a “monomer‐like” state. The TPE units and alkyl chains in Aggr _KP enable their interaction with free monomers in solution, thereby acting as “seed” for catalyzing secondary nucleation. This process leads to the temporal evolution of highly fluorescent, ultralong, rigid bundled fibers as the stable thermodynamic product ( Aggr _TP ). The enhanced fluorescence of Aggr _TP is attributed to the aggregation‐induced emission from the TPE during the bundling of the nanofibers. As a result of secondary‐nucleation‐triggered bundling, Aggr _TP creates multiple micrometer‐long, straight, parallel, 1D hydrophobic lanes. The potential of the hydrophobic lanes in Aggr _TP to serve as a supramolecular template for the long‐range 1D organization of semiconductor nanocrystals without compromising their inherent optical properties is demonstrated.

Synthesizing carbon dots (CDs) using therapeutic compounds as precursors has emerged as a promising strategy for biomedical applications, enabling simultaneous utilization of the beneficial properties of both nanoparticles and bioactive molecules without additional modification. In this work, we report the synthesis of novel CDs (ARI-NCDs) using citric acid, urea, and (E)-2-(2,5-dimethoxyphenyl)­methylenebutane-1,4-dioic acid via a green, one-step hydrothermal process at 200 °C for 10 h. Control CDs prepared from citric acid and urea (U-NCDs) were synthesized identically. Comprehensive characterization by TEM, FT-IR, Raman, XRD and XPS confirmed nitrogen-doped, oxygen-rich surfaces and successful aryl functionalization. ARI-NCDs exhibited bright, nearly excitation-independent blue emission and a higher quantum yield than U-NCDs. TGA revealed the enhanced thermal stability of ARI-NCDs compared with U-NCDs. Zeta potential measurements across pH 4–10 indicated a single well-defined negative surface charge for ARI-NCDs at neutral pH, consistent with superior colloidal stability and dispersion homogeneity, while U-NCDs displayed charge heterogeneity. In vitro assays using HeLa cells demonstrated efficient cellular internalization of ARI-NCDs and low cytotoxicity, highlighting their suitability for live cell imaging and other biomedical applications. Additionally, ARI-NCDs displayed pronounced antibacterial activity against both Gram-positive and Gram-negative bacteria with larger inhibition zones and lower minimum inhibitory concentrations relative to U-NCDs, attributable to the functional groups and structural attributes imparted by the aryl itaconic acid precursor. These findings underscore the versatility of ARI-NCDs for multifunctional biomedical applications, combining imaging capability with antimicrobial efficacy.

The efficacy of chemodynamic cancer therapy is drastically reduced due to the sluggish reaction kinetics of Fenton reactions inside the tumor microenvironment (TME). Hence, it is highly desirable to develop strategies that can improve the reaction kinetics of the Fenton reaction at the TME. Herein, a supramolecular approach for the crafting of a DNA-based chemodynamic therapy (CDT) agent containing dual Fenton reaction centers and a photothermal agent (DNA1some/PDMn/DNA2) for the targeted and enhanced chemodynamic cancer therapy is reported. The nanoformulation exhibited targeted cellular internalization via a receptor-mediated endocytosis mechanism and underwent disassembly at the lysosome, leading to the release of individual components of the nanoformulation, which include (i) Cu²⁺, (ii) Mn⁴⁺, and polydopamine. Reduction of Cu²⁺ and Mn⁴⁺ with intracellular GSH yielded two Fenton reaction centers, Cu⁺ and Mn²⁺, respectively, which underwent Fenton reaction with H₂O₂ to produce ^•OH. Further, photoirradiation of the nanoformulation using an 808 nm laser resulted in a photothermal effect due to the presence of polydopamine. This not only facilitates the cellular apoptosis via the photothermal effect but also improves the efficiency of both Cu⁺- and Mn²⁺-based Fenton reactions. The enhanced therapeutic outcome was due to the synergetic combination of PTT and CDT.

Lumazine synthase (LS), a bacterial protein that self-assembles into 60-mer icosahedral virus-like nanoparticles, has emerged as a promising platform for nanoparticle-based drug delivery and vaccine design. However, detailed biophysical characterization of the LS nanoparticle vaccine has not been well-studied. In this study, we generated LS nanoparticles fused with domain B of protein A (pA-LS), enabling their binding to the hFc-tagged S1 domain of the SARS-CoV-2 spike protein harboring two critical mutations (E484K and D614G) associated with increased infectivity and antibody escape. Biophysical analysis, such as transmission electron microscopy (TEM), revealed an extended size (∼45 nm) compared with the empty particle (∼15 nm). Similarly, atomic force microscopy (AFM) and dynamic light scattering (DLS) analyses confirmed increases in height and diameter. The spike-decorated nanoparticles demonstrated multivalent surface presentation by binding to the ACE2 receptor with a speckle-like appearance. Immunization of mice with pA-LS-S1-hFc elicited neutralizing antibodies against SARS-CoV-2 and its variants. Further, immunization followed by a live SARS-CoV-2 challenge (Wuhan-Hu-1, B.1.617.2 (Delta), or B.1.1.529 (Omicron)) in K18-hACE2 transgenic mice significantly reduced the lung viral load and pathology. Additionally, we generated mosaic nanoparticles displaying spike proteins from two epidemic coronaviruses, SARS-CoV-1 and MERS-CoV, which exhibited binding to their respective cellular receptors, ACE2 and DPP4, with similar binding patterns. Immunization with these mosaic nanoparticles elicited cross-reactive neutralizing antibodies against SARS-CoV-1 and MERS-CoV pseudoviruses. Our proof-of-concept data demonstrate the versatility of the LS nanoparticle platform for antigen presentation, supporting the development of multivalent vaccine designs targeting diverse antigens and contributing to immunogen design strategies.

Rubyrins have been judiciously designed and synthesised to achieve NIR absorption, photostability and reactive oxygen species (ROS) generation. The in vitro studies confirm the NIR light-triggered anticancer activity of these photosensitizers.

Recent years have witnessed the rapid growth of combination therapy for the treatment of cancer. Chemo and antisense DNA therapies are two clinically proven and efficient treatment modalities for cancer. However, direct delivery of both chemo and antisense oligonucleotides into the cancerous cells is challenging and hence there is a high demand for the development of new strategies that permit the direct delivery of chemo and antisense therapeutic agents in a targeted fashion. Herein, we show a supramolecular approach for the direct delivery of hydrophobic chemo drug and cell impermeable antisense oligonucleotide into a cancer cell in a targeted fashion. Synthesis of an amphiphile (DNA1‐CPT) consist of hydrophobic camptothecin (CPT) conjugated to an antisense oligonucleotide (DNA1) via glutathione‐responsive disulphide linker is reported. Self‐assembly of DNA1‐CPT results in the formation of GSH‐responsive NPs with CPT as the hydrophobic core and DNA1 as the hydrophilic shell. Self‐assembled NPs exhibits excellent cellular internalization via endocytosis pathway, and the high concentration of glutathione inside the cancer cells causes the cleavage of disulphide bond of the NPs and trigger the simultaneous release of CPT and DNA1a. Enhanced cytotoxicity is observed for the NPs due to the synergetic combination of chemo and antisense DNA therapies.

A CDT nanoagent loaded with a pH regulator for the improvement of CDT action by decreasing the pH at the TME for targeted cancer therapy is reported.

Floxuridine is a potential clinical anticancer drug for the treatment of various cancers. However, floxuridine typically causes unfavorable side effects due to its very poor tumor selectivity, and, hence, there is a high demand for the development of novel approaches that permit the targeted delivery of floxuridine into cancerous cells. Herein, the design and synthesis of an esterase-responsive multifunctional nanoformulation for the targeted delivery of floxuridine in esterase-overexpressed cancer cells is reported. Photopolymerization of floxuridine-tethered lipoic acid results in the formation of amphiphilic floxuridine-tethered poly(disulfide). Self-assembly of the amphiphilic polymer results in the formation of nanoparticles with floxuridine decorated on the surfaces of the particles. Integration of aptamer DNA for nucleolin onto the surface of the nanoparticle is demonstrated by exploring the base-pairing interaction of floxuridine with adenine. Targeted internalization of the aptamer-decorated nanoparticle into nucleolin-expressed cancer cells is demonstrated. Esterase triggered cleavage of the ester bond connecting floxuridine with the polymer backbone, and the subsequent targeted delivery of floxuridine into cancer cells is also shown. Excellent therapeutic efficacy is observed both in vitro and also in the 3D tumor spheroid model. This noncovalent strategy provides a simple yet effective strategy for the targeted delivery of floxuridine into cancer cells in a less laborious fashion.