Publications by authors named "Reji Varghese"

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Synergetic combination therapy is emerging as one of the most promising approaches for cancer treatment. Among the various therapeutic approaches, PDT has received particular attention due to its non-invasive nature. However, the therapeutic performance of PDT is severely affected by tumour hypoxia.

View Article and Find Full Text PDF

This work extensively studied the vasculature of mice mammary fat pads (BALB/c and C57BL/6) with special reference to haematogenous drainage routes. Mammary fat pads were five pairs (first cervical, second and third thoracic, fourth abdominal and fifth inguinal), bilaterally symmetrical, extending laterally and continuously with the subcutaneous fascia. The superficial cervical artery and vein primarily accomplished the blood vasculature of the first mammary fat pad, while the lateral thoracic and external thoracic arteries and veins supplied the second and third mammary fat pads.

View Article and Find Full Text PDF

Cancer is indisputably one of the major threats to mankind, and hence the design of new approaches for the improvement of existing therapeutic strategies is always wanted. Herein, the design of a tumor microenvironment-responsive, DNA-based chemodynamic therapy (CDT) nanoagent with dual Fenton reaction centers for targeted cancer therapy is reported. Self-assembly of DNA amphiphile containing copper complex as the hydrophobic Fenton reaction center results in the formation of CDT-active DNAsome with Cu-based Fenton catalytic site as the hydrophobic core and hydrophilic ssDNA protrude on the surface.

View Article and Find Full Text PDF

The therapeutic outcome of chemodynamic therapy (CDT) is greatly hindered by the presence of oxidative damage repair proteins (MTH1) inside cancer cells. These oxidative damage repair proteins detoxify the action of radicals generated by Fenton or Fenton-like reactions. Hence, it is extremely important to develop a simple strategy for the downregulation of MTH1 protein inside cancer cells along with the delivery of metal ions into cancer cells.

View Article and Find Full Text PDF

There is huge demand for developing guests that bind β-CD and can conjugate multiple cargos for cellular delivery. We synthesized trioxaadamantane derivatives, which can conjugate up to three cargos per guest. H NMR titration and isothermal titration calorimetry revealed these guests form 1 : 1 inclusion complexes with β-CD with association constants in the order of 10  M .

View Article and Find Full Text PDF

A supramolecular approach for the design of assembly-disassembly-driven F ON/OFF nanoparticles, triggered by specific molecular recognition, for the detection of DNA binding cancer biomarkers is reported. The key to our design strategy is the characteristic F NMR signal of the probe, which completely vanishes in the aggregated state due to the shortening of relaxation. However, molecular recognition of DNA by the cancer biomarkers through specific molecular recognition results in the disassembly of the nanoparticles, which causes the restoration of the characteristic F signal of the probe.

View Article and Find Full Text PDF

Two-component organogels offer several advantages over one-component gels, but their design is highly challenging. Hence, it is extremely important to design new approaches for the crafting of two-component organogels with interesting optical and mechanical properties. Herein, we report the design of a new class of two-component supergelators obtained from the assembly between acid functionalized tetraphenylethylene (TPE)-based dendrons and alkylated melamine.

View Article and Find Full Text PDF

Two major hurdles in NP-based catalysis are the aggregation of the NPs and their recycling. Immobilization of NPs onto a 2D support is the most promising strategy to overcome these difficulties. Herein, amphiphilicity-driven self-assembly of galactose-hexaphenylbenzene-based amphiphiles into galactose-decorated 2D nanosheet is reported.

View Article and Find Full Text PDF

Targeted photodynamic therapy (PDT) is one of the promising approaches for the selective killing of cancerous cells without affecting the normal cells, and hence designing new strategies for targeted PDT is extremely important. Herein we report the design and synthesis of a new class of nanosheets derived from the self-assembly of the iodo-BODIPY-biotin conjugate as a photosensitizer for targeted PDT applications. The nanosheet exhibits a high extinction coefficient in the NIR region, high singlet oxygen efficiency, no toxicity in the dark and cell targeting ligands (biotin) on the surface, which are necessary features required for an ideal photosensitizer.

View Article and Find Full Text PDF

The unparalleled ability of DNA to recognize its complementary strand through Watson and Crick base pairing is one of the most reliable molecular recognition events found in natural systems. This highly specific sequence information encoded in DNA enables it to be a versatile building block for bottom-up self-assembly. Hence, the decoration of functional nanostructures with information-rich DNA is extremely important as this allows the integration of other functional molecules onto the surface of the nanostructures through DNA hybridization in a highly predictable manner.

View Article and Find Full Text PDF

Design of phototheranostic agents in a single step approach is one of the challenges in cancer therapy. Herein, a one-step strategy based on amphiphilicity-driven self-assembly of DNA-BODIPY amphiphiles for the design of a new class of micelles, which offer all three phototheranostic functions, is reported. These include (i) strong emission at NIR (φf = 30%) for imaging, (ii) high photothermal conversion (η = 52%) for PTT and (iii) an ssDNA-based shell for the integration of cell targeting moieties.

View Article and Find Full Text PDF

Design and synthesis of physically (non-covalently) cross-linked nanoparticles through host-guest interaction between β-CD and adamantane is reported. Specific molecular recognition between β-CD functionalized branched DNA nanostructures (host) and a star-shaped adamantyl-terminated 8-arm poly(ethylene glycol) polymer (guest) is explored for the design of the nanoparticles. The most remarkable structural features of DNA nanoparticles include their excellent biocompatibility and the possibility of various non-covalent interactions with both hydrophobic and hydrophilic organic molecules.

View Article and Find Full Text PDF

Nanocarrier-based chemotherapy is one of the most efficient approaches for the treatment of cancer, and hence, the design of new nanocarriers is very important. Herein, the design of a new class of physically cross-linked nanoparticles (nanogel) solely made of biomolecules including DNA, protein, and biotin as a nanocarrier for the targeted cancer therapy is reported. A specific molecular recognition interaction between biotin and streptavidin is explored for the cross-linking of a DNA nanostructure for the crafting of a nanogel.

View Article and Find Full Text PDF

High aspect ratio, sugar-decorated 2D nanosheets are ideal candidates for the capture and agglutination of bacteria. Herein, the design and synthesis of two carbohydrate-based Janus amphiphiles that spontaneously self-assemble into high aspect ratio 2D sheets are reported. The unique structural features of the sheets include the extremely high aspect ratio and dense display of galactose on the surface.

View Article and Find Full Text PDF

Crafting of chiral plasmonic nanostructures is extremely important and challenging. DNA-directed organization of nanoparticle on a chiral template is the most appealing strategy for this purpose. Herein, we report a supramolecular approach for the design of DNA-decorated, helically twisted nanoribbons through the amphiphilicity-driven self-assembly of a new class of amphiphiles derived from DNA and hexaphenylbenzene (HPB).

View Article and Find Full Text PDF

Preventing the aggregation of NPs and their recovery are the two major hurdles in NP based catalysis. Immobilization of NPs on a support has proven to be a promising strategy to overcome these difficulties. Herein we report the design of high aspect ratio two-dimensional (2D) crystalline DNA nanosheets formed from the amphiphilicity-driven self-assembly of DNA-tetraphenylethylene amphiphiles and also demonstrate the potential of DNA nanosheets for the immobilization of catalytically active NPs.

View Article and Find Full Text PDF

Design and synthesis of high aspect ratio 2D nanosheets with surface having ultradense array of information-rich molecule such as DNA is extremely challenging. Herein, we report a universal strategy based on amphiphilicity-driven self-assembly for the crafting of high aspect ratio, 2D sheets that are densely surface-decorated with DNA. Microscopy and X-ray analyses have shown that the sheets are crystalline.

View Article and Find Full Text PDF

Nanogels made of biomolecules are one of the potential candidates as a nanocarrier for drug delivery applications. The unique structural characteristics and excellent biocompatibility of DNA suggest that DNA nanogels would be an ideal candidate. Herein, a general design strategy for the crafting of DNA nanogels with controllable size using the multivalent host-guest interaction between β-CD functionalized branched DNA nanostructures as the host and a star-shaped adamantyl-terminated 8-arm poly(ethylene glycol) polymer as the guest is reported.

View Article and Find Full Text PDF

A pH-responsive DNAsome derived from the amphiphilicity-driven self-assembly of DNA amphiphile containing C-rich DNA sequence is reported. The acidification of DNAsome induces a structural change of C-rich DNA from random coil to an i-motif structure that triggers the disassembly of DNAsome and its subsequent morphological transformation into an open entangled network. The encapsulation of a hydrophobic guest into the membrane of DNAsome and its pH-triggered release upon acidification of DNAsome is also demonstrated.

View Article and Find Full Text PDF

DNA nanostructures have found potential applications in various fields including nanotechnology, materials science and nanomedicine, hence the design and synthesis of DNA nanostructures is extremely important. Self-assembly of DNA amphiphiles provides an efficient strategy for the crafting of soft DNA nanostructures. However, the synthesis of DNA amphiphiles is always challenging.

View Article and Find Full Text PDF