Browsing by Author "Resmi, AN"

Now showing 1 - 7 of 7
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    Bifunctional cysteine gold nanocluster for β-amyloid fibril inhibition and fluorescence imaging: A distinctive approach to manage Alzheimer's disease
    (Journal of Materials Chemistry B, 2023-04) Resmi, AN; Rekha, CR; Dhushyandhun, ME; Sarathkumar, E; Shenoy, SJ; Gulia, KK; Jayasree, RS
    Alzheimer's disease (AD) is a progressive complex neurodegenerative disorder affecting millions of individuals worldwide. Currently, there is no effective treatment for AD. AD is characterized by the deposition of amyloid plaques/fibrils. One major strategy for managing this disease is by slowing the progression of AD using different drugs which could potentially limit free-radical formation, oxidative stress and lipid peroxidation and promote the survival of neurons exposed to β-amyloid. Inhibition of amyloid fibrillization and clearance of amyloid plaques/fibrils are essential for the prevention and treatment of AD. The thiophilic interaction between the side chain of an aromatic residue in a polypeptide and a sulphur atom of the compound can effectively inhibit amyloid fibril formation. In this work, we have synthesized cysteine-capped gold nanoclusters (Cy-AuNCs) which exhibit inherent red emission and can disintegrate amyloid fibrils through the aforementioned thiophilic interactions. Herein, we also used molecular docking to study the thiophilic interactions between the sulphur atom of Cy-AuNCs and the aromatic rings of the protein. Finally, the gold cluster was functionalized with a brain targeting molecule, Levodopa (AuCs-LD), to specifically target the brain and to facilitate passage through the blood brain barrier (BBB). Both Cy-AuNCs and AuCs-LD showed good biocompatibility and the inherent fluorescence properties of nanoclusters enabled real time imaging. The efficacy of the nanoclusters to disintegrate amyloid fibrils and their ability to cross the BBB were demonstrated both in vitro and in vivo in the BBB model and the AD animal model respectively. Our results imply that nanoparticle-based artificial molecular chaperones may offer a promising therapeutic approach for AD.
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    Doxorubicin-Polysorbate 80 conjugates: targeting effective and sustained delivery to the brain
    (RSC pharmaceutics, 2024-05) Ram Prasad, S; Leena, SS; Deepthi, A; Resmi, AN; Jayasree, RS; Sandhya, KS; Jayakrishnan, A
    Targeting therapeutic agents to the brain to treat the central nervous system (CNS) diseases is a major challenge due to the blood-brain-barrier (BBB). In this study, an attempt was made to deliver a model drug such as doxorubicin (DOX) to the brain in a mice model through DOX-Polysorbate 80 (DOX-PS80) conjugates. DOX was successfully conjugated with the non-ionic surfactant Polysorbate 80 (PS80) by carbamate linkage and the conjugate was characterized by different spectroscopic techniques such as FTIR, UV-Visible and NMR. The DOX conjugation efficacy was found to be 43.69 ± 4.72 %. The in vitro cumulative release of DOX from the conjugates was found to be 4.9 ± 0.8 % in PBS of pH 7.3 and 3.9 ± 0.6 % in simulated cerebrospinal fluid (CSF) of pH 7.3 at the end of 10 days. In vitro BBB permeability assay was carried out using bEnd.3 cells and DOX-PS80 conjugate showed a 3-fold increase in BBB permeability compared to controls. In vitro cytotoxicity assay using U251 human glioblastoma cells showed an IC50 value of 38.10 µg/mL for DOX-PS80. Cell uptake studies revealed that DOX-PS80 was effectively taken up (90%) by the bEnd.3 and U251 cells and localized in cytoplasm at the end of 24 h. Tumor spheroid assay and in vivo experiments in Swiss albino mice demonstrated the possibility of DOX-PS80 conjugate crossing the BBB and delivering the drug molecules to the target site for treating CNS disorders.
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    Enhancing chemical signal transformation in lateral flow assays using aptamer-architectured plasmonic nanozymes and para-phenylenediamine
    (Nanoscale, 2025-01) Sarathkumar, E; Jibin, K; Sivaselvam, S; Sharma, AS; Alexandar, V; Resmi, AN; Velswamy, P; Jayasree, RS
    The widespread adoption and commercialization of lateral flow assays (LFAs) for clinical diagnosis have been hindered by limitations in sensitivity, specificity, and the absence of quantitative data. To address these challenges, we developed aptamer-architectured gold nanoparticles as nanozymes that catalytically convert para-phenylenediamine (PPD) into Bandrowski's base (BB), thereby amplifying signal strength and sensitivity. The physiochemical properties of the nanozymes were characterized and their specific binding efficiency was demonstrated using experimental studies. The nanozymes and PPD-based LFA test strips were evaluated for the detection of the COVID-19 spike protein in both test and clinical samples. Notably, we achieved a significant visual detection limit of 168 pg mL−1, with a signal quality enhancement of over 20-fold within 15-minute timeframe. Moreover, we rigorously tested 25 clinical samples to assess the transformative potential of the product, demonstrating a semi-quantitative analysis efficiency exceeding 90%. This performance outstripped commercially available LFA kits (87.5%). Notably, the colorimetric system exhibited an R2 value of 0.9989, a critical factor for clinical testing and industry integration. The incorporation of nanozymes and PPD in LFAs offers a cost-effective solution with significantly improved sensitivity, enabling the detection of ultra-low concentrations (picograms) of spike protein. By addressing key challenges in LFA-based diagnostics, the current technique underscores the potential of this transformative biomedical sensor for industry integration. It also highlights its suitability for commercialization, positioning it as a universal platform for diagnostic applications.
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    Fluorescent carbon dots tailored iron oxide nano hybrid system for in vivo optical imaging of liver fibrosis
    (Methods and Applications in Fluorescence, 2023-03) Nazeer, SS; Saraswathy, A; Nimi, N; Sarathkumar, E; Resmi, AN; Shenoy, SJ; Jayasree, RS
    Hybrid nanoparticles are innovative invention of last decade designed to overcome limitations of single-component nanoparticles by introducing multiple functionalities through combining two or more different nanoparticles. In this study, we are reporting development of magneto-fluorescent hybrid nanoparticles by combining iron oxide and carbon nanoparticles to enablein vivofluorescence imaging which also has all the required characteristic properties to use as Magnetic Resonance Imaging (MRI) contrast agent. In order to achieve dual-functional imaging, alginate and pullulan coated super paramagnetic iron oxide nanoparticles (ASPION and PSPION) and Carbon dots (Cdts) were synthesised separately. ASPIONs and PSPIONs were further chemically conjugated with Cdts and developed dual-functional nanohybrid particles ASPION-Cdts and PSPION-Cdts. Subsequently, evaluation of the materials for its size, functionalisation efficiency, fluorescence and magnetic properties, biocompatibility and cellular uptake efficiency has been carried out. Fluorescence imaging of liver fibrosis was performedin vivoin rodent model of liver fibrosis using the two nanohybrids, which is further confirmed by high fluorescence signal from the harvested liver.
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    Multifunctional amino functionalized graphene quantum dots wrapped upconversion nanoparticles for photodynamic therapy and X-ray CT imaging.
    (Inorganic Chemistry Communications,, 2023-03) Anjusha, AJ; Thirunavukkarasu, S; Resmi, AN; Jayasree, RS; Dhanapandian, S; Krishnakumar, N
    Herein, we designed and developed a multifunctional nanocomposites by complexing NaGdF4:Yb/Er nanoparticles (UCNPs) with amino functionalized graphene quantum dots (af-GQDs). In the as-prepared nanocomposite (af-GQD/UCNPs), properties of UCNPs and af-GQDs were incorporated into a single nanoplatform to endow therapeutic and diagnostic functions. The UCNPs were employed as an imaging probe and a contrast agent for CT imaging, and the af-GQDs served as a therapeutic agent and photosensitizer (PS) by generating singlet oxygen for photodynamic therapy (PDT). Furthermore, the nanocomposites were investigated by electron microscopy, FTIR spectroscopy, zeta potential measurement, UV–vis spectroscopy, upconversion luminescence measurement, and cytotoxicity assessment. The in vitro experiments displayed excellent X-ray attenuation ability and PDT effects of af-GQD/UCNPs. Hence, the proposed multifunctional nanocomposites, which possesses upconversion luminescence, photodynamic, and X-ray attenuation properties, might be a viable option for application in bio-imaging and photodynamic therapy.
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    Nanoarchitectonics of fluorescent gold nanoclusters: A platform for image guided photodynamic therapy of hypoxic tumor
    (Applied Materials Today, 2024-06) Resmi, AN; Sivaselvam, S; Papasouli, E; Kunnumpurathu, J; Praveen, CS; Koukaras, EN; Rerat, M; Karamanis, P; Jayasree, RS
    Metal nanoclusters are atomically precise materials comprising metal core of few atoms exhibiting unique photoluminescence properties, unlike their bigger counterparts. Some metal nanocluster with ligand-to-metal charge transfer, long-lived excited state and excited triplet state contribute to inherent photosensitizing (PS) property. However, the therapeutic efficacy of PDT is hindered by the insufficient oxygen supply (O2) in tumor microenvironment. In the present work, cysteine-capped gold nanocluster (AuC) are studied for their unique molecular architecture for PS efficiency. The co-existence of monodispersed and self-assembled structures contribute to the photoluminescence from the quantum confinement of electronic states and aggregation-induced emission (AIE) based PS property, respectively. In-silico model was performed to study the interaction of cysteine to gold cluster, its ground and excited-state properties and the charge transfer mechanism. The AuC as PS generates cytotoxic radicals in both Type I and Type II photodynamic pathways and the dominant radical species involved were elucidated by EPR spectroscopy. In vitro analysis in HeLa cells showed excellent biocompatibility and bioimaging properties. The intracellular ROS production and Live/Dead assay confirmed the generation of ROS in HeLa cells upon laser irradiation. The image-guided photodynamic property with synergistic Type I and Type II PDT reactions of AuC promises its potential application in cancer therapy in both hypoxic and normoxic conditions
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    Ultrasensitive Detection of Blood-Based Alzheimer’s Disease Biomarkers: A Comprehensive SERSImmunoassay Platform Enhanced by Machine Learning
    (ACS Chemical Neuroscience, 2024-11) Resmi, AN; Nazeer, SS; Dhushyandhun, ME; Paul, Willi; Chacko, BP; Menon, RN; Jayasree, RS
    Accurate and early disease detection is crucial for improving patient care, but traditional diagnostic methods often fail to identify diseases in their early stages, leading to delayed treatment outcomes. Early diagnosis using blood derivatives as a source for biomarkers is particularly important for managing Alzheimer’s disease (AD). This study introduces a novel approach for the precise and ultrasensitive detection of multiple core AD biomarkers (Aβ40, Aβ42, p-tau, and t-tau) using surface-enhanced Raman spectroscopy (SERS) combined with machine-learning algorithms. Our method employs an antibody-immobilized aluminum SERS substrate, which offers high precision, sensitivity, and accuracy. The platform achieves an impressive detection limit in the attomolar (aM) range and spans a wide dynamic range from aM to micromolar (μM) concentrations. This ultrasensitive and specific SERS immunoassay platform shows promise for identifying mild cognitive impairment (MCI), a potential precursor to AD, from blood plasma. Machine-learning algorithms applied to the spectral data enhance the differentiation of MCI from AD and healthy controls, yielding excellent sensitivity and specificity. Our integrated SERS-machine-learning approach, with its interpretability, advances AD research and underscores the effectiveness of a cost-efficient, easy-to-prepare Al-SERS substrate for clinical AD detection.