Browsing by Author "Santhakumar, H"

Now showing 1 - 7 of 7
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    Engineering of Tripeptide-Stabilized Gold Nanoclusters with Inherent Photosensitizing Property for Bioimaging and Photodynamic Therapy
    (ACS Sustainable Chem. Eng, 2023-01) Santhakumar, H; Nair, RV; Govindachar, DM; Periyasamy, G; Jayasree, RS
    Gold nanoclusters have the characteristics of small size, unique optical properties, and eco-friendly synthesis that make them promising candidates for biomedical applications, especially for bioimaging. However, their inherent photochemical activity and therapeutic efficiency are largely unknown and remain unexplored. Here, we report a simple one-step green synthesis procedure for the preparation of two tripeptide-stabilized silver-doped gold nanoclusters (TPGNCs) and their photodynamic therapeutic effect on cancer cells and simultaneous imaging. The custom-designed tripeptides were used for the preparation of silver-doped gold nanoclusters with enhanced fluorescence emission. These TPGNCs exhibited strong red fluorescence with high quantum yield, large Stokes shift, good photostability, and excellent biocompatibility toward normal cells. TPGNCs imparted minimum dark toxicity toward breast cancer cells. These TPGNCs exhibited appreciable photosensitization to generate ROS within the cancer cells triggering loss of mitochondrial membrane potential, leading to apoptotic cell death. The photosensitizing ability of TPGNCs will be a new avenue in the area of photoinduced cancer therapy with negligible side effects.
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    Gold nanorod decorated with cancer drug for multimodal imaging and therapy
    (Faraday Discussions, 2017-12) Nair, RV; Santhakumar, H; Jayasree, RS
    Cancer, a condition with uncontrolled cell division is the second leading cause of death worldwide. The currently available techniques for the imaging and treatment of cancer have their own limitations and hence a combination of more than one modality is expected to increase the efficacy of both diagnosis and treatment. In the present study, we have developed a multimodal imaging and therapeutic system by incorporating a chemotherapeutic drug, mitoxantrone(MTX) onto PEG coated gold nanorods (GNR). Strong absorption in the near-infrared and visible region qualifies GNR as an efficient photo thermal (PTT) agent upon irradiation with either NIR or visible laser. Additionally, enhanced electric field of GNR makes it a suitable substrate for surface enhanced Raman scattering (SERS). Modification of GNR with amino PEG offers biocompatability without affecting its optical property. In order to achieve tumor specificity, GNR-PEG was conjugated with tumor specific marker that can target cancer cells, leaving the normal cells unaffected. The incorporation of fluorescent chemotherapeutic drug mitoxantrone onto GNR-PEG facilitates the chemo therapy as well as fluorescence imaging. The therapeutic efficacy of the developed GNR based system is tracked using fluorescence imaging and Raman imaging. Careful designing of the system also facilitates the controlled release of the drug by photothermal triggering. Llikewise, the imaging modality could be chosen as either Raman or fluorescence to monitor drug release in accordance with irradiation. The physico-chemical properties, and drug release profile under different physiological conditions have been well studied. Finally, the developed system was tested for the therapeutic efficacy using cancer cells, in vitro. The receptor mediated cell uptake was more effective in the folate over expressed cancer cells than in the normal and low expressed cells. Accordingly the percentage of cell death was more in folate over expressed cancer cells which further enhanced due to the effect of dual therapeutic approach. The cell uptake and treatment efficacy was monitored using the fluorescence microscopy and SERS. In conclusion, the developed GNR-PEG-MTX system is found to be an efficient multimodal therapeutic agent against cancer which could be tracked using two different techniques.
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    Luminescent Gold Nanorod to enhance the NIR emission of Photosensitizer for Targeted Cancer Imaging and Dual therapy: Experimental and Theoretical Approach.
    (Chemistry:A European Journal., 2019-11) Nair, RV; Nair, LV; Govindachar, DM; Santhakumar, H; Nazeer, SS; Rekha, CR; Shenoy, SJ; Periyasamy, G; Jayasree, RS
    The strong plasmon absorption in the near‐infrared (NIR) region render gold nano rods (GNR) amenable for biomedical applications, particularly for photo‐thermal therapy. However, these nanostructures have not been explored for their imaging potential because of their weak emission profile. In this study, the weak fluorescence emission of GNR is tuned to match with the absorption of a photosensitizer molecule (PS), and the energy transfer from GNR to PS enhances emission profile of GNR‐PS combination. GNR complexes generally quench the fluorescence emission of nearby chromophores. However, in the present study, through a competition of energy transfer, the complex retains or rather enhances the fluorescence. The excitation dependent energy transfer has been explained experimentally and theoretically using DFT calculations and CIE chromaticity diagram and power spectrum. The final GNR‐PS complex modified for tumor specificity serves as an excellent organ specific theranostic probe for bioimaging and dual modal therapy, both in vitro and in vivo. Principal component analysis designates photodynamic therapy as a better candidate than the photothermal therapy for long term efficacy, in vivo.
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    Nanotheranostic Probe Built on Methylene Blue Loaded Cucurbituril [8] and Gold Nanorod: Targeted Phototherapy in Combination with SERS Imaging on Breast Cancer Cells
    (Journal of Physical Chemistry B, 2021-12) Narayanan, N; Kim, JH; Santhakumar, H; Joseph, MK; Karunakaran, V; Shamjith, S; Saranya, G; Sujai, PT; Jayasree, RS; Burman, I; Maiti, KK
    Recent advancements in a nanoarchitecture platform for safe and effective targeted phototherapy in a synergistic fashion is an absolute necessity in localized cancer therapy. Photothermal and photodynamic therapies (PTT and PDT) are considered as the most promising localized therapeutic intervention for cancer management as they have no long-term side effects and are minimally invasive and affordable. Herein, we have demonstrated a tailor-made nanotheranostic probe in which macrocyclic host cucurbituril [8] (CB[8]) is placed as a glue between two gold nanorods (GNRs) within ∼3 nm gaps in linear nanoassemblies with exquisitely sensitive plasmonics that exert combined phototherapy to investigate the therapeutic progression on human breast cancer cells. Photosensitizer methylene blue was positioned on CB[8] to impart the PDT effect, whereas GNR was responsible for PTT on a single laser trigger ensuring the synchronized phototherapy. Furthermore, the nanoconstruct was tagged with targeting anti-Her2 monoclonal antibody (MB-CB[8]@GNR-anti-Her2) for localized PTT and PDT on Her2 positive SKBR3 cells, subsequent cellular recognition by surface-enhanced Raman spectroscopy (SERS) platform, and further assessment of the combined intracellular phototherapy. Hence, the current strategy is definitely marked as a proof-of-concept straightforward approach that implies the perfect nature of the combined phototherapy to achieve an efficient cancer treatment.
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    Near infrared-emitting multimodal nanosystem for in vitro magnetic hyperthermia of hepatocellular carcinoma and dual imaging of in vivo liver fibrosis
    (Scientific Reports, 2023-08) Nazeer, SS; Saraswathy, A; Nimi, N; Santhakumar, H; Radhakrishnapillai Suma, P; Shenoy, SJ; Jayasree, RS
    Prolonged usage of traditional nanomaterials in the biological field has posed several short- and long-term toxicity issues. Over the past few years, smart nanomaterials (SNs) with controlled physical, chemical, and biological features have been synthesized in an effort to allay these challenges. The current study seeks to develop theranostic SNs based on iron oxide to enable simultaneous magnetic hyperthermia and magnetic resonance imaging (MRI), for chronic liver damage like liver fibrosis which is a major risk factor for hepatocellular carcinoma. To accomplish this, superparamagnetic iron oxide nanoparticles (SPIONs) were prepared, coated with a biocompatible and naturally occurring polysaccharide, alginate. The resultant material, ASPIONs were evaluated in terms of physicochemical, magnetic and biological properties. A hydrodynamic diameter of 40 nm and a transverse proton relaxation rate of 117.84 mM−1 s−1 pronounces the use of ASPIONs as an efficient MRI contrast agent. In the presence of alternating current of 300 A, ASPIONs could elevate the temperature to 45 °C or more, with the possibility of hyperthermia based therapeutic approach. Magnetic therapeutic and imaging potential of ASPIONs were further evaluated respectively in vitro and in vivo in HepG2 carcinoma cells and animal models of liver fibrosis, respectively. Finally, to introduce dual imaging capability along with magnetic properties, ASPIONs were conjugated with near infrared (NIR) dye Atto 700 and evaluated its optical imaging efficiency in animal model of liver fibrosis. Histological analysis further confirmed the liver targeting efficacy of the developed SNs for Magnetic theranostics and optical imaging as well as proved its short-term safety, in vivo.
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    Real Time Imaging and Dynamics of Hippocampal Zn2+ under Epileptic Condition Using a Ratiometric Fluorescent Probe
    (Sci Rep. 2018, 2018-06) Santhakumar, H; Nair, RV; Philips, DS; Shenoy, SJ; Thekkuveettil, A; Ajayaghosh, A; Jayasree, RS
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    Semi-Supervised Nonnegative Matrix Factorization of Wide-Field Fluorescence Microscopic Images for Tissue Diagnosis
    (Microscopy and Microanalysis, 2020-04) Soman, SM; Rekha, CRP; Santhakumar, H; Narendrakumar, U; Jayasree, RS
    This study tests the use of a constrained nonnegative matrix factorization (NMF) algorithm to explore the comparatively new field of chemometric microscopy to support tissue diagnosis. The algorithm can extract the spectral signature and the absolute concentration map of endogenous fluorophores from wide-field microscopic images. The resultant data distinguished normal and fibrous calvarial tissues, based on the changes in their spectral signatures. The absolute concentration map of endogenous fluorophores, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), and lipofuscin were derived from microscopic images and compared with the fluorescence from pure fluorophores. While the absolute concentration of NADH increased, the same of FAD and lipofuscin decreased from a normal to fibrous calvarial condition. An increase in the optical redox ratio, possibly due to the metabolic changes during the development of fibrosis, was observed. Differentiating tissue types using the absolute concentration map was found to be considerably more precise than that achievable with relative concentration. The quantification of fluorophores with reference to the absolute concentration map can eliminate uncertainties due to system responses or measurement details, thereby generating more biologically apposite data. Wide-field microscopy augmented with a constrained NMF algorithm could emerge as an advanced diagnostic tool, potentially heralding the emergence of chemometric microscopy.