Publications by authors named "P M Gopinath"

269 Publications

Nanoemulsions: the rising star of antiviral therapeutics and nano-delivery system - current status and prospects.

Curr Opin Colloid Interface Sci 2021 Mar 30:101458. Epub 2021 Mar 30.

Centre for Nanobiotechnology, VIT University, Vellore-632014, Tamil Nadu, India.

Nanoemulsions (NEs) of essential oil (EO) have significant potential to target microorganisms, especially viruses. They act as a vehicle for delivering antiviral drugs and vaccines. Narrowing of drug discovery pipeline and the emergence of new viral diseases, especially, COVID-19 have created a niche to use nanoemulsions (NEs) for augmenting currently available therapeutic options. Published literature demonstrated that EOs have an inherent broad spectrum of activity across bacterial, fungal, and viral pathogens. The emulsification process significantly improved the efficacy of the active ingredients in the EOs. This article highlights the research findings and patent developments in the last two years especially, in EO antiviral activity, antiviral drug delivery, vaccine delivery, viral resistance development, and repurposing EO compounds against SARS-CoV2.
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http://dx.doi.org/10.1016/j.cocis.2021.101458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007535PMC
March 2021

Reliability Analysis Of Radiological And Intra-operative Loosening In Total Elbow Arthroplasty.

J Shoulder Elbow Surg 2021 Apr 1. Epub 2021 Apr 1.

Shoulder and Elbow Unit, Northern General Hospital, Sheffield, Yorkshire, England.

Background: Revision of Total Elbow Arthroplasties (TEA) are commonly performed due to prosthetic loosening. National Joint Registry (NJR) data shows TEA revisions are becoming increasingly common with 123 TEA revisions performed in 2018 and 76 the previous year. TEA radiological assessment is based on subjective interpretation with no published criteria. We defined TEA loosening by the presence of at least one of the following criteria:1. Progressive widening of bone-cement, bone-prosthesis or cement-prosthesis interface 2. Fragmentation or fracture of cement 3. Prosthetic component migration 4. Bead shedding in porous coated prostheses. Using this definition, we looked at inter-observer and intra-observer agreement of radiological loosening and compared this assessment with intra-operative findings.

Methods: In our tertiary center we conducted a retrospective review to identify TEA revisions performed between November 2008 and July 2018. Radiological implant loosening was independently assessed by 5 orthopedic surgeons. Inter-observer agreement (kappa coefficient) was calculated. The majority's view of radiological loosening was compared with intra-operative findings.

Results: Ninety-three sets of radiographs were identified with implant stability clearly documented in their operation note. Kappa coefficient between assessors for humeral implant loosening was 0.87 (almost perfect). Kappa coefficient for ulna loosening was 0.75 (substantial). Kappa coefficient for radiological and intra-operative findings for humeral loosening and ulna loosening were 0.67 and 0.71, respectively (substantial). Intra-observer reliability for humeral loosening was almost perfect ( = 0.86) and substantial for ulna loosening ( = 0.74).

Conclusion: Our definition of loosening provides a reproducible inter-observer and intra-observer agreement of radiographic component loosening. In our center's experience, radiological findings may not translate to intra-operative findings and we would advise surgical strategies for TEA revision should include the possibility of needing to perform a dual implant exchange.
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http://dx.doi.org/10.1016/j.jse.2021.03.139DOI Listing
April 2021

Thermochemical digestate fertilizer from solid waste: Characterization, labile carbon dynamics, dehydrogenase activity, water holding capacity and biomass allocation in banana.

Waste Manag 2021 Mar 28;123:1-14. Epub 2021 Jan 28.

Kerala Agricultural University - College of Agriculture, Trivandrum 695 522, Kerala, India.

Thermochemical digestion is a rapid technology of biowaste management resulting in the instant production of organic fertilizer. Characterization and assessment of its suitability as an organic fertilizer is essential for recommendation for crop application. Biowaste and the thermochemical digestate were subjected to physicochemical and biochemical characterization and the compost maturity parameters assessed. The product integrated with inorganic fertilizers was tested in an Ultisol grown with banana in comparison with farmyard manure based fertilizers. Temporal variation in soil reaction, water holding capacity, carbon dynamics, dehydrogenase activity and plant biomass were determined. The thermochemical digestate fertilizer had a bulk density (0.76 Mg m), pH (neutral), C:N ratio (16.26), CEC (85.70 cmol kg), CEC/ TOC ratio (3.99), Fertilizing index (4.7) and a Clean index (5.0). Field evaluation revealed enhanced water holding capacity (38.75-83.17%). Total carbon increased with consistently high labile (R = 0.9551) and non labile carbon fractions and the lowest average lability index (0.78). Dehydrogenase activity at harvest enhanced by 72.81%. An even biomass allocation resulted in 38.84% more biomass production in the fruit over farmyard manure based treatments. In addition to ensuring the safety of the environmental ecosystem, the thermochemical digestate conformed to be a quality resource favoring microbial proliferation and carbon sequestration, thereby restraining carbon dioxide emission. The thermochemical digestate fertilizer based nutrition serves the key deliverables of natural resource management, ecofriendly rapid disposal of biowaste and quality organic fertilizer for banana in Ultisols.
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http://dx.doi.org/10.1016/j.wasman.2021.01.002DOI Listing
March 2021

Nitrogen-doped carbon quantum dots conjugated isoreticular metal-organic framework-3 particles based luminescent probe for selective sensing of trinitrotoluene explosive.

Mikrochim Acta 2020 09 1;187(9):536. Epub 2020 Sep 1.

CSIR- Central Scientific Instruments Organization, Chandigarh, 160030, India.

Amine group-containing isoreticular metal-organic framework (IRMOF-3) particles are utilized for the first time as a trinitrotoluene (TNT) sensing material. IRMOF-3 particles are synthesized using zinc nitrate as a metal precursor and 2-amino-1,4-benzenedicarboxylic acid as a linker. The nitrogen-doped carbon quantum dots (NCQDs) are synthesized from citric acid and ethylenediamine as carbon and nitrogen precursor, respectively. The NCQDs are conjugated with IRMOF-3 particles as IRMOF-3/NCQDs. The TEM micrograph revealed the average size of IRMOF-3 particles to be 363.66 nm. The photoluminescence emission intensity of IRMOF-3 particles at λ 430 nm is highly increased in the presence of NCQDs (λ 330 nm). Both the as-synthesized IRMOF-3 and IRMOF-3/NCQD particles are explored for TNT detection to compare the effect of NCQDs on the IRMOF-3 particle surface. Lower limit of detection (7.5 × 10 M) and higher Stern-Volmer constant (4.46 × 10 M) are achieved by IRMOF-3/NCQD particles. The association constant also increased from 5.3 × 10 to 2.78 × 10 M after the conjugation of IRMOF-3 particles with NCQDs. Moreover, enhanced selectivity for TNT over trinitrophenol is achieved using the IRMOF-3/NCQD particles. Graphical Abstract.
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http://dx.doi.org/10.1007/s00604-020-04496-0DOI Listing
September 2020

Development of Sunlight-Driven Reduced Graphene Oxide (rGO)/CeO₂-CuO Nanofibrous Photocatalyst for Efficient Removal of Organic Dyes.

J Nanosci Nanotechnol 2020 Dec;20(12):7480-7494

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India.

A hybrid nanofibrous membrane photocatalysts was developed through electrospinningcarbonization method. In this work, the hybrid membrane with - hetero-structure consisting of CeO₂ and CuO metal-oxide nanoparticles was prepared by a hierarchical and facile approach through electrospun technique and stabilized by hydrothermal process. The obtained heterogeneous photocatalyst membrane was studied for its catalytic properties by performing several experiments using test solutions of anionic Congo red (CR) and cationic methylene blue (MB) dyes, respectively. The as-prepared Graphene-CeO₂/CuO intercalated polyacrylonitrile nanofibrous (GCPNs) membrane is characterized by using various analytical techniques and its photocatalytic degradation properties was studied by conducting batch studies and validated using the kinetics models. Furthermore, the functional group transformation, electronic transition state, binding energy values and chemical oxidation state of the GCPNs membrane before and after degradation was investigated by spectroscopic studies. The optical properties of the GCPNs membrane was further analysed by UV-VIS diffuse reflectance spectroscopy (DRS). Also, the enhanced photo-degradation behaviour of the - hetero-structure due to the suppression of the recombination rate of the photogenerated electron-hole pairs was confirmed by photoluminescence studies (PL). These investigations implied that the developed photocatalyst GCPN membrane follows the pseudo first-order kinetics having higher reaction rate constant. Comprehensively, the GCPN has varying dye removal capacity of 90-98% for Congo red and 30-90% for Methylene blue in which the photocatalytic degradation capacity increases with increase in dye concentration and time. The reusability studies supported the sustainability and durability of the photocatalytic membrane for longer lifetime and practical value. Henceforth, nanotechnology-based cutting-edge technology offers novel hybrid nanomaterials having excellent properties that are pre-requisite for the development of sunlight mediated nano-photocatalytic reactors in the commercial applications.
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http://dx.doi.org/10.1166/jnn.2020.18739DOI Listing
December 2020

Revision total elbow arthroplasty: Is it safe to perform a single-stage revision for presumed aseptic loosening based on clinical assessment, normal inflammatory markers, and a negative aspiration?

J Shoulder Elbow Surg 2021 Jan 10;30(1):140-145. Epub 2020 Jun 10.

Shoulder and Elbow Orthopaedic Department, Northern General Hospital, Sheffield, UK.

Background: Revision total elbow arthroplasty (TEA) is a challenging procedure that is becoming increasingly common. In our unit, we regard it as essential to exclude infection as the underlying cause of TEA loosening. In all patients with arthroplasty loosening, we undertake a careful history and examination, perform radiographs, monitor inflammatory markers, and undertake a joint aspiration. If any investigation suggests infection as the etiology, then a 2-stage revision is undertaken. Open biopsies are not routinely performed. The aim was to ascertain from our outcomes whether it is safe to perform a single-stage revision for presumed aseptic loosening using these criteria.

Methods: A retrospective review of a consecutive series of revision TEAs was performed in our unit over a 10-year period (2008-2018). Single-stage revisions performed for presumed aseptic loosening were identified. Case notes, radiographs, bloods, aspiration results, and microbiology of tissue samples taken at revision were reviewed.

Results: A total of 123 revision elbow arthroplasty cases were performed in the study period. Sixty cases were revised for preoperatively proven infection, instability, or implant failure and were excluded from this study. In 63 cases, aseptic loosening was diagnosed based on history, clinical examination, blood markers, and aspiration. There were 21 dual-component and 42 single-component revisions. In the dual-component revision group, tissue samples taken at the time of revision were positive in only 1 case (5%). In the single-component revision group, positive culture samples were present in 3 cases (7%). χ analysis showed no significant difference between single- and dual-component revisions (P = .76). No cases with positive culture samples from either group have required subsequent revision surgery.

Conclusion: Given the results of this study, we conclude that is safe to perform single-stage revision arthroplasty for implant loosening based on history, examination, normal inflammatory markers, and negative aspiration results without the need for open biopsy.
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http://dx.doi.org/10.1016/j.jse.2020.05.017DOI Listing
January 2021

Dual palladium-photoredox catalyzed chemoselective C-H arylation of phenylureas.

Chem Commun (Camb) 2020 Jun;56(44):5985-5988

Department of Chemistry, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517507, India.

A highly chemoselective C-H arylation of phenylureas has been accomplished using dual palladium-photoredox catalysis at room temperature without any additives, base or external oxidants. Regioselective C-H arylation of N,N'-diaryl substituted unsymmetrical phenylureas has also been accomplished by a careful choice of aryl groups.
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http://dx.doi.org/10.1039/d0cc01443eDOI Listing
June 2020

Systematic approach of chromone skeleton for detecting Mg, ion: Applications for sustainable cytotoxicity and cell imaging possibilities.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Jul 21;235:118290. Epub 2020 Mar 21.

Department of Biotechnology, Indian Institute of Technology-Roorkee, Roorkee 247667, India.

The systematic studies of chromone appended novel chemosensors, favored to Mg ion detection, these were analyzed and characterized by different spectroscopic techniques such as NMR, mass spectroscopy, FTIR and optical techniques. The binding demeanor of the ligands was executed with the library of metal ions and shown the good coordination with Mg ion to the ligand's cavity. Both ligands demonstrated good binding behavior with Mg ion. The ligands represented 1: 1 stoichiometry with Mg ions through Job's plot. The low limit of detection of Mg ion was determined as 2.56 × 10 and 1.28 × 10 for L and L respectively. No interference was occurred in Inference study by foreign metal ions that supported the specific detection of Mg ion among the other metal ions. Further, the cytotoxicity assay test of these chromone appended ligands revealed that both ligands and their respective compound with Mg ion shown negligible toxicity with HeLa cancer cell line. Further, due to the fluorescence properties of the ligands, with or without Mg ion was successfully tested in bioimaging experiment of HeLa cancer cell lines and found that ligands with Mg ions represented good imaging with HeLa cancer cell.
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http://dx.doi.org/10.1016/j.saa.2020.118290DOI Listing
July 2020

Benzisothiazolone Derivatives Exhibit Cytotoxicity in Hodgkin's Lymphoma Cells through NF-κB Inhibition and are Synergistic with Doxorubicin and Etoposide.

Anticancer Agents Med Chem 2020 ;20(6):715-723

Department of Chemistry, Indian Institute of Technology Madras, Chennai, Tamilnadu, India.

Background: The authors investigated the NF-κB inhibitory role of three Benzisothiazolone (BIT) derivatives (1, 2 and 3) in Hodgkin's Lymphoma cells (L428) which constitutively express activated NF-κB. All three compounds showed dose-dependent NF-κB inhibition (78.3, 70.7 and 34.6%) in the luciferase reporter gene assay and were found cytotoxic at IC50 values of 3.3μg/ml, 4.35μg/ml and 13.8μg/ml, respectively by the XTT assay. BIT 1and BIT 2 (but not BIT 3) suppressed both NF-κB subunits p50 and p65 in cytoplasmic and nuclear extracts in a concentration-dependent manner. Furthermore, BIT 1 showed a moderate synergistic effect with the standard chemotherapy drugs etoposide and doxorubicin, whereas BIT 2 and 3 showed a moderate additive effect to antagonistic effect. Cisplatin exhibited an antagonist effect on all the compounds tested under various concentrations, except in the case of 1.56μg/ml of BIT 3 with 0.156μg/ml of cisplatin. The compounds also inhibited the migration of adherent human lung adenocarcinoma cells (A549) in vitro. We conclude that especially BIT 1 and BIT 2 have in vitro anti-inflammatory and anti-cancer activities, which can be further investigated for future potential therapeutic use.

Methods: Inspired by the electrophilic sulfur in Nuphar alkaloids, monomeric and dimeric benzisothiazolones were synthesized from dithiodibenzoic acid and their NF-κB inhibitory role was explored. NF-κB inhibition and cytotoxicity of the synthesized derivatives were studied using luciferase reporter gene assay and XTTassay. Immunocytochemistry studies were performed using L428 cells. Cell migration assay was conducted using the A549 cell line. L428 cells were used to conduct combination studies and the results were plotted using CompuSyn software.

Results: Benzisothiazolone derivatives exhibited cytotoxicity in Hodgkin's Lymphoma cells through NF-κB inhibition. Potent compounds showed suppression of both NF-κB subunits p50 and p65 in a concentrationdependent manner, both in cytoplasmic and nuclear extracts. Combination studies suggest that benzisothiazolone derivatives possess a synergistic effect with etoposide and doxorubicin. Furthermore, the compounds also inhibited the migration of A549 cells.

Conclusion: Benzisothiazolones bearing one or two electrophilic sulfur atoms as part of the heterocyclic framework exhibited cytotoxicity in Hodgkin's Lymphoma cells through NF-κB inhibition. In addition, these derivatives also exhibited a synergistic effect with etoposide and doxorubicin along with the ability to inhibit the migration of A549 cells. Our study suggests that BIT-based new chemical entities could lead to potential anticancer agents.
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http://dx.doi.org/10.2174/1871520620666200213103513DOI Listing
January 2020

Bladder Stones Associated with an Aggressive Plasmacytoid Variant of Urothelial Cancer: A Rare Case and Literature Review.

Curr Urol 2020 Jan 7;13(4):217-223. Epub 2020 Jan 7.

Department of Urology, Princes Alexandra Hospital, Harlow, UK.

Urothelial carcinoma is the most common histologic subtype of bladder cancer, accounting for approximately 90%. We herein report a case of a 78-year-old man with an unusual association of bladder stones with an aggressive plasmacytoid variant of urothelial cancer. Initially he presented in 2009 with a very large bladder stone and was treated by an open cystolithotomy. Histology from a bladder biopsy at that time was benign. He failed to attend follow-up appointments but subsequently he attended in 2016 with a recurrent urinary tract infection and an acute kidney injury. A CT scan showed multiple bladder stones. The cause of our patients' multiple bladder stones is unclear and unusual. He then underwent a further open cystolithotomy according to our multidisciplinary team recommendation. Post-operatively he unfortunately developed a non-healing vesicocutaneous fistula for which he was performed cystoscopy and biopsy but ended with transurethral resection due to the extent of abnormal/necrotic tissue. Histology confirmed a plasmacytoid variant of urothelial cancer. To our knowledge, this is the first case of an association of bladder stones with a plasmacytoid variant of urothelial cancer.
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http://dx.doi.org/10.1159/000499268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977006PMC
January 2020

Role of Post-translational Modifications in Alzheimer's Disease.

Chembiochem 2020 04 30;21(8):1052-1079. Epub 2020 Jan 30.

Bioorganic Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Jakkur P.O., Bengaluru, 560064, Karnataka, India.

The global burden of Alzheimer's disease (AD) is growing. Valiant efforts to develop clinical candidates for treatment have continuously met with failure. Currently available palliative treatments are temporary and there is a constant need to search for reliable disease pathways, biomarkers and drug targets for developing diagnostic and therapeutic tools to address the unmet medical needs of AD. Challenges in drug-discovery efforts raise further questions about the strategies of current conventional diagnosis; drug design; and understanding of disease pathways, biomarkers and targets. In this context, post-translational modifications (PTMs) regulate protein trafficking, function and degradation, and their in-depth study plays a significant role in the identification of novel biomarkers and drug targets. Aberrant PTMs of disease-relevant proteins could trigger pathological pathways, leading to disease progression. Advancements in proteomics enable the generation of patterns or signatures of such modifications, and thus, provide a versatile platform to develop biomarkers based on PTMs. In addition, understanding and targeting the aberrant PTMs of various proteins provide viable avenues for addressing AD drug-discovery challenges. This review highlights numerous PTMs of proteins relevant to AD and provides an overview of their adverse effects on the protein structure, function and aggregation propensity that contribute to the disease pathology. A critical discussion offers suggestions of methods to develop PTM signatures and interfere with aberrant PTMs to develop viable diagnostic and therapeutic interventions in AD.
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http://dx.doi.org/10.1002/cbic.201900573DOI Listing
April 2020

Site-Specific Hyperphosphorylation Inhibits, Rather than Promotes, Tau Fibrillization, Seeding Capacity, and Its Microtubule Binding.

Angew Chem Int Ed Engl 2020 03 28;59(10):4059-4067. Epub 2020 Jan 28.

Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland.

The consistent observation of phosphorylated tau in the pathology of Alzheimer's disease has contributed to the emergence of a model where hyperphosphorylation triggers both tau disassociation from microtubules and its subsequent aggregation. Herein, we applied a total chemical synthetic approach to site-specifically phosphorylate the microtubule binding repeat domain of tau (K18) at single (pS356) or multiple (pS356/pS262 and pS356/pS262/pS258) residues. We show that hyperphosphorylation of K18 inhibits 1) its aggregation in vitro, 2) its seeding activity in cells, 3) its binding to microtubules, and 4) its ability to promote microtubule polymerization. The inhibition increased with increasing the number of phosphorylated sites, with phosphorylation at S262 having the strongest effect. Our results argue against the hyperphosphorylation hypothesis and underscore the importance of revisiting the role of site-specific hyperphosphorylation in regulating tau functions in health and disease.
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http://dx.doi.org/10.1002/anie.201913001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065254PMC
March 2020

TiO doped chitosan/poly (vinyl alcohol) nanocomposite film with enhanced mechanical properties for application in bone tissue regeneration.

Int J Biol Macromol 2020 Jan 4;143:285-296. Epub 2019 Dec 4.

Department of Chemical Engineering, Indian Institute of Technology Roorkee, 247667, India. Electronic address:

Here, TiO nanoparticles have been doped into the polymer film-construct of Chitosan/poly (vinyl alcohol)/Nano-hydroxyapatite (CPHT I - III) to enhance the mechanical and biological properties of the film so as to mimic the human bone extracellular matrix for application in human bone regeneration. The synthesized films are highly porous in nature along with the presence of macrovoids. Significantly enhanced mechanical properties were obtained upon the addition of TiO in comparison to previous literature. Increasing content of n-HAP-TiO increased the elasticity, tensile strength of the films and the antibacterial efficacy against both Gram-Positive and Gram-Negative Bacteria. The pH of CPHT I-III films in saline remained in the low alkalinity range of (7.48-7.53) on day 14. CPHT I-III films were compatible with the human erythrocytes as their hemolysis was well below the limit of acute hemolysis. The in-vitro studies revealed the highly cytocompatible nature of CPHT III (15% n-HAP-TiO) for osteoblast-like MG - 63 cell attachment and proliferation. The study has revealed that CPHT III has the potential to be used for bone tissue regeneration, our future studies will be focused on the in-vivo investigations to establish its use in clinical settings.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.11.246DOI Listing
January 2020

Redox responsive xylan-SS-curcumin prodrug nanoparticles for dual drug delivery in cancer therapy.

Mater Sci Eng C Mater Biol Appl 2020 Feb 23;107:110356. Epub 2019 Oct 23.

Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Saharanpur Campus, Paper Mill Road, Saharanpur, 247001, Uttar Pradesh, India. Electronic address:

Chemotherapeutic agents with different anticancer mechanisms could enhance therapeutic effect in cancer therapy by their combined application. In this study, redox-sensitive prodrug nanoparticles based on Xyl-SS-Cur conjugate were developed for co-delivery of curcumin and 5-FU in cancer therapy. The Xyl-SS-Cur conjugate was synthesized via covalent conjugation of curcumin to xylan through a disulphide (-S-S-) linkage. The Xyl-SS-Cur conjugate could self-assemble in aqueous medium into nanoparticles and the lipophilic 5-fluorouracil-stearic acid (5-FUSA) prodrug was encapsulated into the hydrophobic core of Xyl-SS-Cur NPs through dialysis membrane method. The obtained Xyl-SS-Cur/5-FUSA NPs had an appropriate size (∼217 ± 2.52 nm), high drug loading of curcumin (∼ 31.4 wt%) and 5-FUSA (∼ 11.8 wt%) and high stability. The interaction of Xyl-SS-Cur/5-FUSA NPs with blood components was investigated by hemolysis study. The cytotoxicity study demonstrated that Xyl-SS-Cur/5-FUSA NPs induced higher cytotoxicity than free drugs against the Human colorectal cancer cells (HT-29, HCT-15). These results indicate that Xyl-SS-Cur/5-FUSA NPs can serve as a promising drug delivery system in cancer therapy.
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http://dx.doi.org/10.1016/j.msec.2019.110356DOI Listing
February 2020

Nasal septal perforation in systemic lupus erythematosus.

Eur J Rheumatol 2019 07 19;6(3):161-162. Epub 2018 Dec 19.

Department of Otorhinolaryngology, Aster Medcity, Kerala, India.

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http://dx.doi.org/10.5152/eurjrheum.2018.18111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668638PMC
July 2019

Carica papaya loaded poly (vinyl alcohol)-gelatin nanofibrous scaffold for potential application in wound dressing.

Mater Sci Eng C Mater Biol Appl 2019 Oct 30;103:109834. Epub 2019 May 30.

Department of Biotechnology, Indian Institute of Technology Roorkee, India; Center for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India. Electronic address:

Bioactive polymers are highly used polymers for preparing electrospun nanofiber based scaffold in the field of wound dressing to treat chronic non-healing wounds. Here, we report, the fabrication and evaluation of Carica papaya incorporated poly (vinyl) alcohol (PVA) blended gelatin nanofibers. PVA/Gelatin/Carica papaya nanofibrous scaffold was fabricated by electrospinning method. The obtained nanofibrous scaffold was characterized by using various analytical techniques such as FTIR, XRD, TEM, FESEM, AFM, and TGA. The average diameter of these nanofibers was found in the range 140-160 nm using FESEM. This scaffold showed excellent antibacterial activity against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria. The hemocompatibility was analyzed using platelet adhesion test. The cytotoxic activity of these nanofibrous scaffold against fibroblast cells (NIH 3T3) was studied and found no cytotoxic effect. Therefore, these results substantiated that Carica papaya loaded PVA/Gelatin nanofibrous scaffold could be a promising candidate for wound healing application.
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http://dx.doi.org/10.1016/j.msec.2019.109834DOI Listing
October 2019

Corrigendum to "Lipophilic 5-fluorouracil prodrug encapsulated xylan-stearic acid nanoparticles for colon cancer therapy" [Int. J. Biol. Macromol., 128, 2019, 204-213].

Int J Biol Macromol 2019 08 26;135:1273. Epub 2019 Jun 26.

Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India. Electronic address:

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http://dx.doi.org/10.1016/j.ijbiomac.2019.06.070DOI Listing
August 2019

Assessment on interactive prospectives of nanoplastics with plasma proteins and the toxicological impacts of virgin, coronated and environmentally released-nanoplastics.

Sci Rep 2019 06 20;9(1):8860. Epub 2019 Jun 20.

Centre for Nanobiotechnology, Vellore Institute of Technology (VIT), Vellore, 632014, TN, India.

Recently, the concerns about micro- and nano-plastics (NPs) toxicity have been increasing constantly, however the investigations are quiet meager. The present study provides evidences on the toxicological prospectives of virgin-, coronated- and isolated-NPs on human blood cells and Allium cepa root tip, respectively. Several plasma proteins displayed strong affinity towards NPs and produced multi-layered corona of 13 nm to 600 nm size. The coronated-NPs often attracted each other via non-specific protein-protein attraction which subsequently induced protein-induced coalescence in NPs. In the protein point of view, the interaction caused conformational changes and denaturation of protein thereby turned it as bio-incompatible. The coronated-NPs with increased protein confirmation changes caused higher genotoxic and cytotoxic effect in human blood cells than the virgin-NPs. On the other hand, virgin-NPs and the NPs isolated from facial scrubs hindered the root growth and caused chromosome aberration (ring formation, C-mitotic and chromosomal breaks, etc.) in root of Allium cepa. At the outset, the present study highlights the urgent need of scrutinization and regulation of NPs use in medical applications and pre-requisition of additional studies for assessing the bio-accumulation and bio-magnification of NPs.
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http://dx.doi.org/10.1038/s41598-019-45139-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586940PMC
June 2019

Lipophilic 5-fluorouracil prodrug encapsulated xylan-stearic acid conjugates nanoparticles for colon cancer therapy.

Int J Biol Macromol 2019 May 23;128:204-213. Epub 2019 Jan 23.

Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakha nd-247667, India. Electronic address:

In this study, self-assembled nanoparticles based on amphiphilic xylan-stearic acid (Xyl-SA) conjugates have been developed for the efficient delivery of 5-fluorouracil (5-FU) in cancer therapy. The self-assembled behavior of Xyl-SA conjugates in aqueous medium was investigated using pyrene as fluorescent probe. To enhance the loading efficacy of 5-FU, the lipophilic 5-fluorouracil-stearic acid (5-FUSA) prodrug was synthesized and subsequently encapsulated into the hydrophobic core of Xyl-SA NPs. The obtained Xyl-SA/5-FUSA NPs had an appropriate size (~278 nm), high drug loading of 5-FUSA (~14.6 wt%) and high physiological stability. The interaction of the Xyl-SA/5-FUSA NPs with blood components was investigated by hemolysis study. The cell cytotoxic studies demonstrated that Xyl-SA/5-FUSA NPs induced higher cytotoxicity than free drugs against the Human colorectal cancer cells (HT-29, HCT-15). These results indicate that Xyl-SA/5-FUSA NPs can serve as a promising drug delivery system for the efficient delivery of 5-FU in cancer therapy.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.01.101DOI Listing
May 2019

Halogen Substituents in the Isoquinoline Scaffold Switches the Selectivity of Inhibition between USP2 and USP7.

Chembiochem 2019 01 14;20(2):282-286. Epub 2018 Dec 14.

Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel.

Deubiquitinases are important components of the protein regulatory network and, hence, constitute a tempting drug target. We report herein structure-activity relationship studies to develop halogen-substituted isoquionoline-1,3-dione-based inhibitors of the deubiquitinase USP2. In contrast to our previous reports, the best compound discovered was found to act through a reactive oxygen species independent, uncompetitive mechanism with an IC of 250 nm. We show the crucial role of halogens in the common scaffold to provide potency and selectivity of our compound, where the introduction of the fluorine atom completely switches the selectivity of the inhibitor between USP2 and USP7. Our cellular studies highlight the potential applicability of the reported compound for in vivo experiments. The discovery of the isoquinoline-1,3-dione core and the knowledge obtained with regard to halogen substituents provide a platform towards understanding USP2 inhibition and the development of highly selective next-generation deubiquitinase inhibitors.
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http://dx.doi.org/10.1002/cbic.201800612DOI Listing
January 2019

Evaluation of surface properties of low density polyethylene (LDPE) films tailored by atmospheric pressure non-thermal plasma (APNTP) assisted co-polymerization and immobilization of chitosan for improvement of antifouling properties.

Mater Sci Eng C Mater Biol Appl 2019 Jan 31;94:150-160. Epub 2018 Aug 31.

Department of Physics, Institute of Chemical Technology, Matunga, Mumbai 400 019, India.

This work describes the development of antifouling functional coatings on the surface of low density polyethylene (LDPE) films by means of atmospheric pressure non-thermal plasma (APNTP) assisted copolymerization using a mixture of acrylic acid and poly (ethylene glycol). The aim of the study was to investigate the antifouling properties of the plasma copolymerized LDPE films and the same was carried out as a function of deposition time with fixed applied potential of 14 kV. In a second stage, the plasma copolymerized LDPE films were functionalized with chitosan (CHT) to further enhance its antifouling properties. The surface hydrophilicity, structural, topographical and chemistry of the plasma copolymerized LDPE films were examined by contact angle (CA), X-ray diffraction (XRD), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). Coating stability was also studied in detail over a storage time of 15 days by storing in water and air. The antifouling properties of the plasma copolymerized LDPE films were examined via protein adsorption and platelet adhesion studies. CA study showed significant changes in surface wettability after the coating process. XPS and FTIR analysis proved the presence of a dense multifunctional coating and an efficient immobilization of CHT. Substantial amendments in surface topography were observed, positively enhancing the overall surface hydrophilicity. Finally, in-vitro analysis showed excellent antifouling behavior of the surface modified LDPE films.
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http://dx.doi.org/10.1016/j.msec.2018.08.062DOI Listing
January 2019

Genomic amplification of BCR-ABL1 fusion gene and its impact on the disease progression mechanism in patients with chronic myelogenous leukemia.

Gene 2019 Feb 3;686:85-91. Epub 2018 Nov 3.

Laboratory of Cytogenetics and Molecular Diagnostics, Division of Cancer Research, Regional Cancer Centre, Medical College Post, Thiruvananthapuram 695011, Kerala, India. Electronic address:

Identification of BCR-ABL1 fusion gene amplification status is critically important in the effective management of chronic myelogenous leukemia (CML) patients. Earlier reports suggested that overexpression of BCR-ABL1 either through amplification of BCR-ABL1 fusion gene or by the up regulation of BCR-ABL1 transcript level might be an early phenomenon in the establishment of IM resistance and disease evolution in CML. In the current study, we performed dual color dual fusion locus specific BCR/ABL1 FISH analysis along with karyotype analysis using GTG banding (G-banding using trypsin and Giemsa) technique in 489 patients with different clinical stages of CML at diagnosis or during the course of the disease to unravel the spectrum of BCR-ABL1 fusion gene amplification status. Among the study group analyzed, it was found that prevalence of occurrence of BCR-ABL1 fusion gene amplification was significantly higher in advanced stages of disease and in IM resistant CML-CP patients when compared to initial stage of disease, de novo CML-CP. Cytogenetic and metaphase FISH characterization on our study samples revealed that BCR-ABL1 fusion gene amplification was occurred through the formation of extra copies Ph chromosomes and isoderived Ph chromosomes. Current study suggests that unrestrained activity of BCR-ABL1 played a vital role in resistance to targeted therapy and disease evolution in CML. In our study population, patients in progressive stage CML and in IM resistant CP with multiple copies of BCR-ABL1 fusion gene displayed a poor response to targeted treatment with IM. Hence, the early identification of BCR-ABL1 fusion gene amplification using FISH technique will lead to improved interventions and outcome in future CML patients.
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http://dx.doi.org/10.1016/j.gene.2018.11.005DOI Listing
February 2019

Molecular encapsulator-appended poly(vinyl alcohol) shroud on ferrite nanoparticles. Augmented cancer-drug loading and anticancer property.

Mater Sci Eng C Mater Biol Appl 2018 Dec 27;93:125-133. Epub 2018 Jul 27.

Radiochemistry branch, Department of Chemistry, GSP-1 Moscow State University, Leninskie Gory, 119991 Moscow, Russia. Electronic address:

Magnetic nanoparticles (MNPs) have the potency to deliver cancer drugs assisted by the application of a magnetic field. In this paper, we present the design of magnesium ferrite nanoparticles of size suitable for drug delivery. A coating polymer, poly(vinyl alcohol), tethered with a tapered cone-shaped cyclic oligosachcharide, β-cyclodextrin (β-CD) is synthesized and used to wrap and disperse the MNPs. The magnetic properties are explored using vibrating sample magnetometry and Mössbauer spectroscopy. The ∑130 nm MNPs, shrouded with the PVA-CD conjugate allows a high amount of the cancer drug, camptothecin, to be loaded on the nanocarrier. Cytotoxicity studies reveal that the loaded drug retains its potency against HEK 293 cells and the cells are sensitive to the treatment by the drug-loaded nanocarrier.
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http://dx.doi.org/10.1016/j.msec.2018.07.058DOI Listing
December 2018

Strategy of metal iron doping and green-mediated ZnO nanoparticles: dissolubility, antibacterial and cytotoxic traits.

Toxicol Res (Camb) 2017 Nov 30;6(6):854-865. Epub 2017 Aug 30.

Department of Chemical Engineering , National Institute of Technology , Tiruchirappalli 620015 , India . Email: ; ; Tel: +91-431-2503120.

Undoped and Fe-doped ZnO nanoparticles (NPs) were synthesized using leaf extract as a reducing agent. The physicochemical traits, dissolution, cytotoxicity, as well as the antioxidant, photocatalytic and antibacterial activities of synthesized NPs were investigated. The results revealed that ZnO NPs were rod shaped with hexagonal phase structure, and their crystal size, dissolubility and aggregation decreased with Fe doping of NPs. Cytotoxicity of the NPs was studied against MCF-7 cells by MTT assay. IC values for undoped and 1 wt% Fe-doped ZnO NPs were found to be 400 and 600 μg mL, respectively. Cell viability with Fe-doped ZnO NPs was higher than with undoped ZnO. Among the synthesized NPs, -mediated 1 wt% Fe-doped ZnO shows a better decolourization efficiency of 97% for indigo carmine dye under solar irradiance. The antibacterial activity of NPs was tested against Gram-negative and Gram-positive using disc diffusion, minimum inhibitory concentration and growth curve method. The bactericidal activity of Fe-doped ZnO NPs was more prominent with than bacteria and when compared to undoped ZnO.
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http://dx.doi.org/10.1039/c7tx00093fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062353PMC
November 2017

Prognostic Implications of Derivative Chromosome 9 Deletions in Patients with Advanced-Stage Chronic Myelogenous Leukemia.

J Environ Pathol Toxicol Oncol 2018 ;37(2):117-126

Laboratory of Cytogenetics and Molecular Diagnostics, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India.

Elucidation of cryptic BCR/ABL1 gene rearrangement is exceptionally important in the clinical diagnosis and prognosis of chronic myelogenous leukemia (CML). Previous reports indicated an adverse prognostic effect of atypical BCR/ABL1 gene rearrangements with submicroscopic ABL1-BCR deletions on derivative chromosome 9 [der(9)] in CML patients. Dual color dual fusion locus-specific BCR/ABL1 fluorescent in situ hybridization (FISH) analysis together with G-banding using trypsin and Giemsa (GTG banding) was performed in 489 patients at different stages of CML to investigate the spectrum of BCR/ABL1 gene rearrangements. Among the study group analyzed, a significantly higher frequency of BCR/ABL1 gene rearrangements that is consistent with der(9) deletion were observed in the blast crisis (BC) phase at 41.67%, followed by the accelerated phase (AP) at 36.84%, the imatinib mesylate (IM)-resistant chronic phase (CP) at 23.08%, and the lowest incidence was found in de novo CP at 16.61%. 1R1G1F (1 red, 1 green, 1 fusion) with concurrent loss of ABL1-BCR fusion gene on der(9) chromosome was the major signal pattern identified in each group. The results from the current study show that this unusual BCR/ABL1 gene rearrangement is one of the steering forces toward disease progression in CML. Patients in AP/BC of CML with der(9) deletion showed poor response to IM therapy; however, patients with der(9) deletion in the early phases of CML responded well to IM treatment. Therefore, the establishment of an atypical FISH signal pattern in CML is of paramount important because it is associated with adverse clinical prognostic implications in advanced stages of the disease.
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http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2018026023DOI Listing
August 2018

RP-HPLC-UV Method for Estimation of Fluorouracil-Epirubicin-Cyclophosphamide and Their Metabolite Mixtures in Human Plasma (Matrix).

J Chromatogr Sci 2018 Jul;56(6):488-497

Department of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai, Tamil Nadu, India.

A combination of 5-fluorouracil (FU), epirubicin (EP) and cyclophosphamide (CP) is routinely employed in the treatment of breast cancer. The objective of this study was to develop a reverse phase high-performance liquid chromatography (HPLC)-UV method for simultaneous quantitative analysis of the triple-drug and their metabolites in plasma. RP-HPLC system with a C18 column and a diode array detector was employed. The plasma samples were precipitated with acetonitrile and the supernatant was dried under a flow of nitrogen gas. The mobile phase comprised of two combinations, water (pH 4.0) and methanol (98:2 v/v), and water (pH 4.0):methanol:acetonitrile (70:13:17 v/v/v). The retention times for the compounds were determined and the parameters of validation established in plasma indicated the robustness and reliability. The corresponding HPLC peaks were confirmed using electron spray ionization mass spectrometry. FU and metabolites had a recovery of >93%; EP, epirubicinol and CP were >78% from plasma. Stability at 28-30°C in water (pH 4.0) of FU, 5,6-dihydro-5-fluorouracil and EP were higher followed by CP, EPol, fluorodeoxyuridine and fluorouridine (FUR). Storage of the drug-spiked plasma at -80°C assessed for 72 h showed a small but significant (P < 0.05) change in the recovery of FUR and EP. The method was validated in patient's plasma samples (n = 6).
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http://dx.doi.org/10.1093/chromsci/bmy020DOI Listing
July 2018

pH-responsive prodrug nanoparticles based on xylan-curcumin conjugate for the efficient delivery of curcumin in cancer therapy.

Carbohydr Polym 2018 May 7;188:252-259. Epub 2018 Feb 7.

Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand-247667, India. Electronic address:

In the present study, novel pH-responsive prodrug nanoparticles based on xylan-curcumin (xyl-cur) conjugate were developed to enhance the therapeutic efficacy of curcumin in cancer therapy. The synthesis of xyl-cur conjugate (prodrug) was confirmed by FT-IR, H NMR, UV-vis and fluorescence spectroscopy. The xyl-cur prodrug was subsequently self-assembled in to nanoparticles (xyl-cur prodrug NPs) in an aqueous medium with the average particle size 253 nm and the zeta potential of -18.76 mV. The xyl-cur prodrug NPs were highly pH-sensitive in nature and most of the drug was released at lower pH. The interaction of the xyl-cur prodrug NPs with blood components was tested by hemolysis study. The cytotoxic activity of the xyl-cur prodrug NPs against human colon cancer cells (HT-29, HCT-15) demonstrated that the prodrug NPs exhibits greater cytotoxic effect than curcumin. Therefore, these results reveal that xyl-cur prodrug NPs could be a promising candidate for improving the intracellular delivery of curcumin in cancer therapy.
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http://dx.doi.org/10.1016/j.carbpol.2018.02.006DOI Listing
May 2018

Polysaccharide Functionalized Single Walled Carbon Nanotubes as Nanocarriers for Delivery of Curcumin in Lung Cancer Cells.

J Nanosci Nanotechnol 2018 Mar;18(3):1534-1541

Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India.

Nanoscale drug delivery systems have emerged as promising alternatives to overcome the problems associated with by conventional chemotherapy for cancer treatment such as poor drug stability and bio-distribution. Herein, we report a single walled carbon nanotubes (SWCNTs) based drug delivery system functionalized with polysaccharides such as alginate (ALG) and chitosan (CHI), which can be loaded with an anticancer drug curcumin (CUR). Modification of SWCNTs renders high drug loading efficiency and sustained drug release, imperative for drug activity. These were characterized through various tools viz, microscopic (transmission electron microscopy, scanning electron microscopy and atomic force microscopy) and zeta potential analysis. Incorporation of CUR inside the modified SWCNTs was studied through Fourier transform infrared spectroscopy, fluorescence and UV-visible spectroscopy. In vitro release studies were conducted to gain an insight into the pH-dependent release behavior of the entrapped CUR from modified SWCNTs. The anti-cancer potential was further demonstrated using human lung adenocarcinoma (A549) cells as a model system. Various cell culture based assays were performed to study the ability of released CUR from modified SWCNTs for inhibiting the cancer cell proliferation by inducing apoptosis.
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http://dx.doi.org/10.1166/jnn.2018.14222DOI Listing
March 2018

Niclosamide loaded biodegradable chitosan nanocargoes: an study for potential application in cancer therapy.

R Soc Open Sci 2017 Nov 8;4(11):170611. Epub 2017 Nov 8.

Nanobiotechnology Laboratory, Centre of Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.

Chitosan nanoparticles can advance the pharmacological and therapeutic properties of chemotherapeutic agents by controlling release rates and targeted delivery process, which eliminates the limitations of conventional anti-cancer therapies and they are also safe as well as cost-effective. The aim of present study is to explore the anti-tumour effect of niclosamide in lung and breast cancer cell lines using biocompatible and biodegradable carrier where nanoparticles loaded with hydrophobic drug (niclosamide) were synthesized, characterized and applied as a stable anti-cancer agent. Niclosamide loaded chitosan nanoparticles (Nic-Chi Np's) of size approximately 100-120 nm in diameter containing hydrophobic anti-cancer drug, i.e. niclosamide, were prepared. Physico-chemical characterization confirms that the prepared nanoparticles are spherical, monodispersed and stable in aqueous systems. The therapeutic efficacy of Nic-Chi Np's was evaluated against breast cancer cell line (MCF-7) and human lung cancer cell line (A549). MTT assay reveals the cell viability of the prepared Nic-Chi Np's against A549 and MCF-7 cells and obtained an IC value of 8.75 µM and 7.5 µM, respectively. Acridine orange/ethidium bromide dual staining results verified the loss of the majority of the cells by apoptosis. Flow cytometer analysis quantified the generation of intracellular reactive oxygen species (ROS) and signified that exposure to a higher concentration (2 × IC) of Nic-Chi Np's resulted in elevated ROS generation. Notably, Nic-Chi Np treatment showed more apoptosis and cell death in MCF-7 as compared to A549. Further, the remarkable induction of apoptosis by Nic-Chi Np's was confirmed by semi-quantitative reverse transcription polymerase chain reaction, scanning electron microscopy and cell-cycle analysis. Thus, Nic-Chi Np's may have a great potential even at low concentration for anti-cancer therapy and may replace or substitute more toxic anti-mitotic drugs in the near future.
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http://dx.doi.org/10.1098/rsos.170611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717630PMC
November 2017

Antimicrobial photodynamic therapy: Single-walled carbon nanotube (SWCNT)-Porphyrin conjugate for visible light mediated inactivation of Staphylococcus aureus.

Colloids Surf B Biointerfaces 2018 Feb 20;162:108-117. Epub 2017 Nov 20.

Centre of Excellence: Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, 247667, India; Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, 247667, India. Electronic address:

Due to the excessive use of antibiotics over the years, the microorganisms have developed resistance to numerous drugs. The growth of multi-resistant organisms (MROs) heads due to the insufficient treatment with the currently available medications which present a great threat to the biotic component of the environment as well as to the food technology sectors. The goal of this research was to develop a nano-composite made up of single-walled carbon nanotubes (SWCNTs) and amine-functionalized porphyrin, which could further be used for the anti-microbial studies in presence of visible light showing photodynamic effect to inactivate cells. Photodynamic antimicrobial chemotherapy is gaining significant interest due to its capabilities as an innovative form of antimicrobial treatment. The development of anti-microbial photodynamic therapy (a-PDT) is a non-antibiotic access to inactivate microorganisms. We examined the synthesis of amine-functionalized porphyrin and conjugated it to the oxidised single-walled carbon nanotubes (SWCNTs). By the use of appropriate amount of single-walled carbon nanotubes (SWCNTs), we have shown the interaction between the porphyrin conjugated nanotubes and the bacterial cells in presence of visible light led to the cell membrane damage, concluding that SWCNT-porphyrin conjugates can be used as an antibacterial agent. The characterization of the oxidised SWCNT and SWCNT-porphyrin conjugates was determined by field emission scanning electron microscopy (FE-SEM), which provides detailed information about the composition and the morphological analysis. The particle size measurements were carried out by transmission electron microscopy (TEM). On investigating under the florescence microscopy, red fluorescence was observed. Thus, these properties demand us to design this facile material comprised of SWCNT-aminoporphyrin conjugates that shows potent antibacterial activity.
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http://dx.doi.org/10.1016/j.colsurfb.2017.11.046DOI Listing
February 2018