Niranjan Meher
@niperraebareli.edu.in
Assistant Professor Biotechnology
NIPER Raebareli
RESEARCH, TEACHING, or OTHER INTERESTS
Cancer Research, Chemistry, Organic Chemistry, Biotechnology
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Anju Wadhwa, Sinan Wang, Bonell Patiño-Escobar, Anil P. Bidkar, Kondapa Naidu Bobba, Emily Chan, Niranjan Meher, Scott Bidlingmaier, Yang Su, Suchi Dhrona,et al.
American Association for Cancer Research (AACR)
Abstract Purpose: Multiple myeloma is a plasma cell malignancy with an unmet clinical need for improved imaging methods and therapeutics. Recently, we identified CD46 as an overexpressed therapeutic target in multiple myeloma and developed the antibody YS5, which targets a cancer-specific epitope on this protein. We further developed the CD46-targeting PET probe [89Zr]Zr-DFO-YS5 for imaging and [225Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of prostate cancer. These prior studies suggested the feasibility of the CD46 antigen as a theranostic target in multiple myeloma. Herein, we validate [89Zr]Zr-DFO-YS5 for immunoPET imaging and [225Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of multiple myeloma in murine models. Experimental Design: In vitro saturation binding was performed using the CD46 expressing MM.1S multiple myeloma cell line. ImmunoPET imaging using [89Zr]Zr-DFO-YS5 was performed in immunodeficient (NSG) mice bearing subcutaneous and systemic multiple myeloma xenografts. For radioligand therapy, [225Ac]Ac-DOTA-YS5 was prepared, and both dose escalation and fractionated dose treatment studies were performed in mice bearing MM1.S-Luc systemic xenografts. Tumor burden was analyzed using BLI, and body weight and overall survival were recorded to assess antitumor effect and toxicity. Results: [89Zr]Zr-DFO-YS5 demonstrated high affinity for CD46 expressing MM.1S multiple myeloma cells (Kd = 16.3 nmol/L). In vitro assays in multiple myeloma cell lines demonstrated high binding, and bioinformatics analysis of human multiple myeloma samples revealed high CD46 expression. [89Zr]Zr-DFO-YS5 PET/CT specifically detected multiple myeloma lesions in a variety of models, with low uptake in controls, including CD46 knockout (KO) mice or multiple myeloma mice using a nontargeted antibody. In the MM.1S systemic model, localization of uptake on PET imaging correlated well with the luciferase expression from tumor cells. A treatment study using [225Ac]Ac-DOTA-YS5 in the MM.1S systemic model demonstrated a clear tumor volume and survival benefit in the treated groups. Conclusions: Our study showed that the CD46-targeted probe [89Zr]Zr-DFO-YS5 can successfully image CD46-expressing multiple myeloma xenografts in murine models, and [225Ac]Ac-DOTA-YS5 can effectively inhibit the growth of multiple myeloma. These results demonstrate that CD46 is a promising theranostic target for multiple myeloma, with the potential for clinical translation.
Kondapa Naidu Bobba, Anil P. Bidkar, Anju Wadhwa, Niranjan Meher, Suchi Drona, Alexandre M. Sorlin, Scott Bidlingmaier, Li Zhang, David M. Wilson, Emily Chan,et al.
Ivyspring International Publisher
Anil P. Bidkar, Sinan Wang, Kondapa Naidu Bobba, Emily Chan, Scott Bidlingmaier, Emily A. Egusa, Robin Peter, Umama Ali, Niranjan Meher, Anju Wadhwa,et al.
American Association for Cancer Research (AACR)
Abstract Purpose: Radiopharmaceutical therapy is changing the standard of care in prostate cancer and other malignancies. We previously reported high CD46 expression in prostate cancer and developed an antibody–drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody. Experimental Design: [225Ac]DOTA-YS5 was developed, and its therapeutic efficiency was tested on cell-derived (22Rv1, DU145), and patient-derived (LTL-545, LTL484) prostate cancer xenograft models. Biodistribution studies were carried out on 22Rv1 tumor xenograft models to confirm the targeting efficacy. Toxicity analysis of the [225Ac]DOTA-YS5 was carried out on nu/nu mice to study short-term (acute) and long-term (chronic) toxicity. Results: Biodistribution study shows that [225Ac]DOTA-YS5 agent delivers high levels of radiation to the tumor tissue (11.64% ± 1.37%ID/g, 28.58% ± 10.88%ID/g, 29.35% ± 7.76%ID/g, and 31.78% ± 5.89%ID/g at 24, 96, 168, and 408 hours, respectively), compared with the healthy organs. [225Ac]DOTA-YS5 suppressed tumor size and prolonged survival in cell line–derived and patient-derived xenograft models. Toxicity analysis revealed that the 0.5 μCi activity levels showed toxicity to the kidneys, likely due to redistribution of daughter isotope 213Bi. Conclusions: [225Ac]DOTA-YS5 suppressed the growth of cell-derived and patient-derived xenografts, including prostate-specific membrane antigen–positive and prostate-specific membrane antigen–deficient models. Overall, this preclinical study confirms that [225Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46-targeted radioligand therapy in prostate cancer.
Niranjan Meher, Henry F. VanBrocklin, David M. Wilson, and Robert R. Flavell
MDPI AG
Targeted nanotheranostic systems offer significant benefits due to the integration of diagnostic and therapeutic functionality, promoting personalized medicine. In recent years, prostate-specific membrane antigen (PSMA) has emerged as an ideal theranostic target, fueling multiple new drug approvals and changing the standard of care in prostate cancer (PCa). PSMA-targeted nanosystems such as self-assembled nanoparticles (NPs), liposomal structures, water-soluble polymers, dendrimers, and other macromolecules are under development for PCa theranostics due to their multifunctional sensing and therapeutic capabilities. Herein, we discuss the significance and up-to-date development of “PSMA-targeted nanocarrier systems for radioligand imaging and therapy of PCa”. The review also highlights critical parameters for designing nanostructured radiopharmaceuticals for PCa, including radionuclides and their chelators, PSMA-targeting ligands, and the EPR effect. Finally, prospects and potential for clinical translation is discussed.
Kondapa Naidu Bobba, Anil P. Bidkar, Niranjan Meher, Cyril Fong, Anju Wadhwa, Suchi Dhrona, Alex Sorlin, Scott Bidlingmaier, Becka Shuere, Jiang He,et al.
Society of Nuclear Medicine
Visual Abstract 225Ac-targeted α-radiotherapy is a promising approach to treating malignancies, including prostate cancer. However, α-emitting isotopes are difficult to image because of low administered activities and a low fraction of suitable γ-emissions. The in vivo generator 134Ce/134La has been proposed as a potential PET imaging surrogate for the therapeutic nuclides 225Ac and 227Th. In this report, we detail efficient radiolabeling methods using the 225Ac-chelators DOTA and MACROPA. These methods were applied to radiolabeling of prostate cancer imaging agents, including PSMA-617 and MACROPA-PEG4-YS5, for evaluation of their in vivo pharmacokinetic characteristics and comparison to the corresponding 225Ac analogs. Methods: Radiolabeling was performed by mixing DOTA/MACROPA chelates with 134Ce/134La in NH4OAc, pH 8.0, at room temperature, and radiochemical yields were monitored by radio–thin-layer chromatography. In vivo biodistributions of 134Ce-DOTA/MACROPA.NH2 complexes were assayed through dynamic small-animal PET/CT imaging and ex vivo biodistribution studies over 1 h in healthy C57BL/6 mice, compared with free 134CeCl3. In vivo, preclinical imaging of 134Ce-PSMA-617 and 134Ce-MACROPA-PEG4-YS5 was performed on 22Rv1 tumor–bearing male nu/nu-mice. Ex vivo biodistribution was performed for 134Ce/225Ac-MACROPA-PEG4-YS5 conjugates. Results: 134Ce-MACROPA.NH2 demonstrated near-quantitative labeling with 1:1 ligand-to-metal ratios at room temperature, whereas a 10:1 ligand-to-metal ratio and elevated temperatures were required for DOTA. Rapid urinary excretion and low liver and bone uptake were seen for 134Ce/225Ac-DOTA/MACROPA. NH2 conjugates in comparison to free 134CeCl3 confirmed high in vivo stability. An interesting observation during the radiolabeling of tumor-targeting vectors PSMA-617 and MACROPA-PEG4-YS5—that the daughter 134La was expelled from the chelate after the decay of parent 134Ce—was confirmed through radio–thin-layer chromatography and reverse-phase high-performance liquid chromatography. Both conjugates, 134Ce-PSMA-617 and 134Ce-MACROPA-PEG4-YS5, displayed tumor uptake in 22Rv1 tumor–bearing mice. The ex vivo biodistribution of 134Ce-MACROPA.NH2, 134Ce-DOTA and 134Ce-MACROPA-PEG4-YS5 corroborated well with the respective 225Ac-conjugates. Conclusion: These results demonstrate the PET imaging potential for 134Ce/134La-labeled small-molecule and antibody agents. The similar 225Ac and 134Ce/134La-chemical and pharmacokinetic characteristics suggest that the 134Ce/134La pair may act as a PET imaging surrogate for 225Ac-based radioligand therapies.
Niranjan Meher, Gary W. Ashley, Anil P. Bidkar, Suchi Dhrona, Cyril Fong, Shaun D. Fontaine, Denis R. Beckford Vera, David M. Wilson, Youngho Seo, Daniel V. Santi,et al.
American Chemical Society (ACS)
Tumoral uptake of large-size nanoparticles is mediated by the enhanced permeability and retention (EPR) effect, with variable accumulation and heterogenous tumor tissue penetration depending on the tumor phenotype. The performance of nanocarriers via specific targeting has the potential to improve imaging contrast and therapeutic efficacy in vivo with increased deep tissue penetration. To address this hypothesis, we designed and synthesized prostate cancer-targeting starPEG nanocarriers (40 kDa, 15 nm), [89Zr]PEG-(DFB)3(ACUPA)1 and [89Zr]PEG-(DFB)1(ACUPA)3, with one or three prostate-specific membrane antigen (PSMA)-targeting ACUPA ligands. The in vitro PSMA binding affinity and in vivo pharmacokinetics of the targeted nanocarriers were compared with a nontargeted starPEG, [89Zr]PEG-(DFB)4, in PSMA+ PC3-Pip and PSMA– PC3-Flu cells, and xenografts. Increasing the number of ACUPA ligands improved the in vitro binding affinity of PEG-derived polymers to PC3-Pip cells. While both PSMA-targeted nanocarriers significantly improved tissue penetration in PC3-Pip tumors, the multivalent [89Zr]PEG-(DFB)1(ACUPA)3 showed a remarkably higher PC3-Pip/blood ratio and background clearance. In contrast, the nontargeted [89Zr]PEG-(DFB)4 showed low EPR-mediated accumulation with poor tumor tissue penetration. Overall, ACUPA conjugated targeted starPEGs significantly improve tumor retention with deep tumor tissue penetration in low EPR PC3-Pip xenografts. These data suggest that PSMA targeting with multivalent ACUPA ligands may be a generally applicable strategy to increase nanocarrier delivery to prostate cancer. These targeted multivalent nanocarriers with high tumor binding and low healthy tissue retention could be employed in imaging and therapeutic applications.
Niranjan Meher, Debasish Barman, Retwik Parui, and Parameswar Krishnan Iyer
Royal Society of Chemistry (RSC)
This review explores the up-to-date development of fluorescence-based detection of volatile organic contaminants (VOCs) on multiple platforms mainly highlighting mechanistic prospect that could help the future structural design of smart VOC sensors.
Retwik Parui, Niranjan Meher, and Parameswar Krishnan Iyer
Royal Society of Chemistry (RSC)
A unique fluorometric and colorimetric “light-up” sensing strategy has been conceptualized to detect chloroform and distinguish various volatile chlorinated solvents (VCSs) along with “dual-phase” security ink application.
Niranjan Meher, Kyounghee Seo, Sinan Wang, Anil P. Bidkar, Miko Fogarty, Suchi Dhrona, Xiao Huang, Ryan Tang, Charles Blaha, Michael J. Evans,et al.
American Chemical Society (ACS)
Boron neutron capture therapy (BNCT) is an encouraging therapeutic modality for cancer treatment. Prostate-specific membrane antigen (PSMA) is a cell membrane protein that is abundantly overexpressed in prostate cancer and can be targeted with radioligand therapies to stimulate clinical responses in patients. In principle, a spatially targeted neutron beam together with specifically targeted PSMA ligands could enable prostate cancer-targeted BNCT. Thus, we developed and tested PSMA-targeted poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles (NPs) loaded with carborane and tethered to the radiometal chelator deferoxamine B (DFB) for simultaneous positron emission tomography (PET) imaging and selective delivery of boron to prostate cancer. Monomeric PLGA-b-PEGs were covalently functionalized with either DFB or the PSMA ligand ACUPA. Different nanoparticle formulations were generated by nanoemulsification of the corresponding unmodified and DFB- or ACUPA-modified monomers in varying percent fractions. The nanoparticles were efficiently labeled with 89Zr and were subjected to in vitro and in vivo evaluation. The optimized DFB(25)ACUPA(75) NPs exhibited strong in vitro binding to PSMA in direct binding and competition radioligand binding assays in PSMA(+) PC3-Pip cells. [89Zr]DFB(25) NPs and [89Zr]DFB(25)ACUPA(75) NPs were injected to mice with bilateral PSMA(-) PC3-Flu and PSMA(+) PC3-Pip dual xenografts. The NPs demonstrated twofold superior accumulation in PC3-Pip tumors to that of PC3-Flu tumors with a tumor/blood ratio of 25; however, no substantial effect of the ACUPA ligands was detected. Moreover, fast release of carborane from the NPs was observed, resulting in a low boron delivery to tumors in vivo. In summary, these data demonstrate the synthesis, characterization, and initial biological assessment of PSMA-targeted, carborane-loaded PLGA-b-PEG nanoparticles and establish the foundation for future efforts to enable their best use in vivo.
Mst Nasima Khatun, Anamika Dey, Niranjan Meher, and Parameswar Krishnan Iyer
American Chemical Society (ACS)
Niranjan Meher, Anil Parsram Bidkar, Debasish Barman, Siddhartha Sankar Ghosh, and Parameswar Krishnan Iyer
Royal Society of Chemistry (RSC)
A simple strategy of conformational manipulation has been unveiled to fine-tune the photophysical and supramolecular self-assembly properties of small molecular systems, which subsequently regulates their biological activities.
Arvin Sain Tanwar, Niranjan Meher, Laxmi Raman Adil, and Parameswar Krishnan Iyer
Royal Society of Chemistry (RSC)
The precise study of fluorescence-based sensing mechanisms and a step-by-step design experiment for the elucidation of the mechanism of sensing for newly designed sensing systems can be ascertained using the presented tutorial review.
Mst Nasima Khatun, Arvin Sain Tanwar, Niranjan Meher, and Parameswar Krishnan Iyer
Wiley
AbstractThe development of a new naphthalene appended naphthalimide derivative (NMI) with aggregation‐induced enhanced emission (AIEE) property for the sensitive detection of 4‐nitroaniline (4‐NA) in aqueous media is presented here. The newly designed naphthalimide AIEEgen has an exceptional blue‐shifted condensed state emission that is devoid of any receptor site, accomplished ultrasensitive detection of 4‐NA, which is one of the broad‐spectrum pesticides that belong to the class III toxic chemical, at parts per billion level (LOD/36 ppb, Ksv=4.1×104 m−1) in water with excellent selectivity even in the presence of potentially competing aliphatic and aromatic amines. The reported probe is the first of its kind, demonstrating major advantages of receptor‐free inner filter effect (IFE) mechanism for the sensitive detection of 4‐NA using an AIEEgenic probe. Excellent sensitivity for 4‐NA is also achieved on paper‐based test‐strip for low‐cost on‐site detection.
Mrutyunjay Maharana, Niharika Baruah, Sisir Kumar Nayak, Niranjan Meher, and Parameswar Krishnan Iyer
Institute of Electrical and Electronics Engineers (IEEE)
Vegetable oils (VOs) are based on natural ester oil that is considered as an alternative to mineral oil for transformer applications. The dispersion of nanofillers into the VO is expected to improve the physicochemical and electrical performances. Surface-modified insulating nanoparticle is dispersed into the VO to prepare the VO-based nanofluid (NF). An open-beaker oxidative aging study is carried out at 115 °C for VO and NF at three distinct aging durations such as 100, 300, and 500 h. Alterations in the molecular level of aged VO and NF are studied through the various spectroscopic and physicochemical analyses such as nuclear magnetic resonance, Fourier transform infrared, UV-vis absorbance, fluorescence, color, acid number, interfacial tension, and flash point. The fluorescence-based analysis is carried out for VO and NF at fresh and aged condition to monitor the comparative aging degradation. Oxidative aging of VO and NF results in the formation of flammable and harmful gases, which are analyzed using dissolved gas analysis technique. A comparative analysis of the electrical properties such as ac breakdown voltage, dielectric constant, and dielectric dissipation factor for fresh and aged sample of VO and NF is studied.
Rahul Narasimhan Arunagirinathan, Niranjan Meher, and Parameswar Krishnan Iyer
American Chemical Society (ACS)
For almost a decade, organic nonvolatile memory incorporating an inorganic metal/semiconductor nanoparticles in organic polymers have been well-established in fabricating the resistive switching me...
Niranjan Meher and Parameswar Krishnan Iyer
Royal Society of Chemistry (RSC)
A simple synthetic tweak of functional group engineering has been unveiled to fine-tune the supramolecular self-assembly and condensed state photophysical properties in small molecular system with effective control on ACQ/AIEE regulation.
Priyanka Dutta, Niranjan Meher, Akhtar Hussain Malik, Bhaben Choudhury, and Parameswar Krishnan Iyer
American Chemical Society (ACS)
A new highly conjugated polymer–bioconjugate poly[9,9-bis(6′-adenine) hexyl)fluorene-co-4,7-(2,1,3 benzothiadiazole)] (PFBT-A) is developed using the well-known Pd(PPh3)4-catalyzed Suzuki cross-coupling polymerization reaction with a simple purification method. PFBT-A showed excellent sensitivity toward the iron containing metalloprotein and the well-known cancer biomarker ferritin with a detection limit as low as 0.164 nM (i.e., 71.05 ng/mL), which is much below the ferritin level observed in the blood serum of cancer patients. Detailed mechanistic study confirmed the presence of static ground state complexation and electrostatic interaction between the probe and the analyte, leading to quenching in fluorescence intensity of the probe. Real-time applications with the probe were performed in the unspiked serum samples of two normal people and two cancer patients (carcinoma valva and chronic myeloid leukemia) with significantly high ferritin content. Further analysis of PFBT-A in spiked normal blood serum ...
Sayan Roy Chowdhury, S. N. Balaji, Subrata Mondal, Niranjan Meher, Vishal Trivedi, and Parameswar Krishnan Iyer
American Chemical Society (ACS)
Amyloid aggregation is observed in many neurodegenerative diseases, but the formation of final plaque seldom correlates to the disease severity. Early and intermediate structures such as soluble oligomers are considered as primary toxic species in protein misfolding diseases specifically linked to Aβ in Alzheimer's disease (AD). Two peptide-linked perylenebisimide isomers (PAPAP and APPPA) were developed to study the structure-activity relationship with a toxic Aβ oligomer in commercial Aβ as well as in human cerebrospinal fluid (CSF), diminish and inhibit them, and prevent them from forming toxic amyloid fibrils from an early stage. Self-aggregation of perylenebisimides enables the formation of nano/micro-objects that are used to interact with the hydrophobic regions of the peptide and direct the peptide aggregation into an "off-pathway", preventing mature fibril formation. Remarkably, one of the Ala-Phe dipeptide-linked perylenebisimide isomers (APPPA) showed a high selectivity toward an Aβ oligomer and could also cross the endothelial monolayer barrier (blood-brain barrier, BBB) more efficiently than the other derivative (PAPAP). Kinetic ThT studies and AFM imaging provided strong proof of both of the isomers being able to inhibit fibrillation of prefibrillar and oligomeric Aβ in both the commercial Aβ1-40 peptide as well as in the real human CSF sample. Further, a correlation has been built using pristine fluorescence of perylenebisimides, showing modulation and "oligo-blocking". The obtained data provides clear evidence that the mutual aggregation between the modulator and amyloid aggregate becomes predominant compared to their individual aggregation. These results reinforce the development of the structural platform design to diminish toxic oligomers, inhibit them, and prevent the formation of toxic amyloid fibrils at an early stage.
Niranjan Meher and Parameswar Krishnan Iyer
Wiley
Niranjan Meher and Parameswar Krishnan Iyer
Wiley
AbstractA simple design strategy of long alkyl chain substitution was formulated to block the detrimental π–π interaction that potentially transforms the aggregation‐caused quenching (ACQ) chromophores into aggregation‐induced emission (AIE) active smart nanomaterials. The long octadecyl pendant chain substituted naphthalimide (NI) derivatives self‐assembled into fluorescent nanosheets (NS)‐like structures that spontaneously have surfaces coated with NI cores in water. The fluorescent NS were subsequently used to recognize the organic volatile contaminants (OVCs) at ppb levels via an acceptor‐excited photoinduced electron transfer (a‐PET) mechanism, unveiled as the first representative example. A new design strategy is thereby provided to detect toxic xylene derivatives in water using smart nanomaterials.
Peddaboodi Gopikrishna, Niranjan Meher, and Parameswar Krishnan Iyer
American Chemical Society (ACS)
This comprehensive review surveys the up-to-date development of aggregation-induced emission/aggregation-induced emission enhancement (AIE/AIEE) active naphthalimide (NI)-based smart materials with potential for wide and real-world applications and that serves as a highly versatile building block with tunable absorption and emission in the complete visible region. The review article commences with a precise description of the importance of NI moiety and its several restricted area of applications owing to its aggregation caused quenching (ACQ) properties, followed by the discovery and importance of AIE/AIEE-active NIs. The introduction section tracked an overview of the state of the art in NI luminogens in multiple applications. It also includes a few mechanistic studies on the structure-property correlation of NIs and provides more insights into the condensed-state photophysical properties of small aggregation-prone systems. The review aims to ultimately accomplish current and forthcoming views comprising the use of the NIs for the detection of biologically active molecules, such as amino acids and proteins, recognition of toxic analytes, fabrication of light emitting diodes, and their potential in therapeutics and diagnostics.
Niranjan Meher, Swagatika Panda, Sachin Kumar, and Parameswar Krishnan Iyer
Royal Society of Chemistry (RSC)
A new concept of formyl group induced ACQ to AIEE transformation is established in naphthalimide congeners. Also, ultradetection of hydrazine via Schiff base complexation over multiple platforms is presented.
Niranjan Meher and Parameswar Krishnan Iyer
Royal Society of Chemistry (RSC)
Strategically, a series of five angular "V" shaped naphthalimide AIEEgens with varying pendant chains (butyl, hexyl, octyl, cyclohexyl and methylcyclohexyl) have been synthesized to fine-tune their nanomorphological and photophysical properties. With similar aromatic cores and electronic states, unexpected tuning of the condensed state emission colors and nanomorphologies (reproducible on any kind of surface) of naphthalimides has been achieved for the first time simply by varying their side chains. Conclusive analysis by various spectroscopic techniques (SC-XRD, powder-XRD, DLS, FESEM) and DFT computational studies confirmed the full control of the pendant chain (in terms of bulkiness around the naphthalimide core, which restricts the ease of intermolecular π-π interactions) over the nanoaggregate morphology and solid state emissive properties of the AIEEgens; this can be rationalized to all aggregation-prone systems. These comprehensive studies establish a conceptually unique yet simple and effective method to precisely tune the nanomorphologies and the emission colors of aggregation-prone small organic molecules by judicious choice of the non-conjugated pendant chain. Thus, considering the prime role of the active layer nanomorphology in all organic optoelectronic devices, this methodology may emerge as a promising tool to improve device performance. Among all the congeners, the hexyl chain-containing congener (HNQ) forms well-defined nanoribbons with smaller diameters (as confirmed from DLS: 166 nm and FESEM: 150 nm) and provides a larger surface area. Consequently, the HNQ-nanoribbons were employed as a fluorescent sensor for the discriminative detection of trinitrophenol (TNP) in pure aqueous media. FE-SEM images revealed that, upon gradual addition of TNP (10 nM to 100 μM), these nanoribbons undergo an aggregation/disaggregation process, forming non-fluorescent co-aggregates with TNP, and provide highly enhanced sensitivity compared to existing state-of-the-art on aggregation-prone systems. Fluorescence titration studies confirmed that HNQ can detect the presence of TNP as low as 16.8 ppb and can serve as a cost-effective portable device incorporated with UV-light for on-site visual detection of TNP, even in the presence of potentially competing nitroaromatic compounds.
Sayan Roy Chowdhury, Mahesh Agarwal, Niranjan Meher, Balakrishnan Muthuraj, and Parameswar Krishnan Iyer
American Chemical Society (ACS)
Inhibitory modulation toward de novo protein aggregation is likely to be a vital and promising therapeutic strategy for understanding the molecular etiology of amyloid related diseases such as Alzheimer's disease (AD). The building up of toxic oligomeric and fibrillar amyloid aggregates in the brain plays host to a downstream of events, causing damage to axons, dendrites, synapses, signaling, transmission, and finally cell death. Herein, we introduce a novel conjugated polymer (CP), hydroxyquinoline appended polyfluorene (PF-HQ), which has a typical "amyloid like" surface motif and exhibits inhibitory modulation effect on amyloid β (Aβ) aggregation. We delineate inhibitory effects of PF-HQ based on Thioflavin T (ThT) fluorescence, atomic force microscopy (AFM), circular dichroism (CD), and Fourier transform infrared (FTIR) studies. The amyloid-like PF-HQ forms nano coaggregates by templating with toxic amyloid intermediates and displays improved inhibitory impacts toward Aβ fibrillation and diminishes amyloid cytotoxicity. We have developed a CP based modulation strategy for the first time, which demonstrates beneficiary amyloid-like surface motif to interact efficiently with the protein, the pendant side groups to trap the toxic amyloid intermediates as well as optical signal to acquire the mechanistic insight.
Niranjan Meher, Sayan Roy Chowdhury, and Parameswar Krishnan Iyer
Royal Society of Chemistry (RSC)
A core substituted naphthalimide AIEEgen displays unusual nanoribbon growth in aqueous media with ultra-sensitivity towards non-heme protein ferritin at physiological conditions.