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Nanoscale metal−organic frameworks: an emerging versatile tool for next‐generation photodynamic therapy
No full textPhotodynamic therapy has emerged as a potent strategy for treatment of cancer due to its non-invasiveness, minimal toxicity, high spatial selectivity, and potential for combination therapies. However, self-aggregation of photosensitizers, tumour hypoxia and low penetration depth of excitation photons remain prominent challenges towards its clinical application. Nanoscale metal-organic frameworks have emerged as one of the most promising materials due to their tunable composition which allows the adjustment of optical and chemical properties by changing the metal ions or organic linkers. Due to their high porosity, they serve as carriers for photosensitizers and demonstrate high tumour accumulation rates, target specificity, and penetration depth with enhanced permeability and retention effect. This review aims to explore recent developments in nanoscale metal-organic frameworks focusing on the design strategies to enhance their effectiveness in tumour microenvironment. Specifically, we have examined the approaches to address challenges posed by hypoxic tumour environment and tissue penetration depth of the various light sources. Furthermore, this review provides insights into the targeting strategies that improve the overall efficacy through stimulus-activated release and sub-cellular internalization of photosensitizers. Finally, we discussed the on-going challenges and some future directions for harnessing their full potential as therapeutic agents for effective outcome of photodynamic therapy
Ferroptosis escape in AML stem cells uncovered by single-cell profiling and reversed by STAT3/NRF2 inhibition
No full textChemo resistant Leukemic stem cells (LSCs) with leukemia re-initiating potential are a key contributor to relapse refractory disease in acute myeloid leukemia (AML), which confers an adverse outcome. These LSCs are primarily enriched in the CD34+CD38- compartment that also harbours healthy HSCs, posing a challenge in their specific elimination. Considering AML as a multi-clonal malignancy, single-cell multi-omics approach was undertaken to identify chemoresistance-associated genes/ pathways in AML LSCs for their potential targeted therapeutics.
For single cell whole transcriptome analysis, we enriched CD34+CD38- or CD34-CD117+CD38- leukemic stem cells isolated from bone marrow aspirates of adult patients with de novo AML (n=12) after informed consent. For differential gene expression analysis scRNAseq was also performed from CD34+ hematopoietic stem cells obtained from healthy donor controls. The DGE analysis of LSCs relative to HSCs identifiedsignificantly altered chemoresistance-associated genes of which, ferritin heavy chain 1 (FTH1) a key player in iron storage within the cells was substantially downregulated in LSCs indicating iron dependency. Altered Ferroptosis related gene (FRGs) expression including FTH1, TFRC, GPX4 and NFE2L2/NRF2 was validated by qPCR. Bioinformatic analysis revealed a common STAT3 binding motif in the promoter region of FRGs. Ferroptosis model was generated in AML cell lines including LSC-like AML cell line MA9 using Erastin or RSL3. These cells were treated with STAT3 inhibitor C188-9 or STAT3-NRF2 dual inhibitor (Brusatol) and the effect on cell proliferation was determined using CCK-8 assay, gene expression by qPCR, flow cytometry was used for the detection of lipid ROS levels by Bodipy dye and intracellular iron estimation were performed. Western blotting was carried out for pSTAT3 and GPX4 protein expression, and colony forming assay was performed with or without the indicated inhibitors.
We identified highly dysregulated FRGs, i.e., FTH1, GPX4, NRF2 and suppression of the ferroptosis pathway in LSCs relative to non-LSCs and HSCs. STAT3 emerged as a transcription factor with a common binding sequence present in the promoter region of FRGs. We demonstrated that STAT3 inhibitor C-188-9 reduced lipid ROS levels and altered FRG expression, but this approach was insufficient to promote ferroptosis. Treatment of AML cells with STAT3 inhibitor alone upregulated NRF2, a transcription factor involved in antioxidant response, thus opposing the ferroptosis-mediated cell death in AML cells. To overcome NRF2-mediated resistance, we further blocked NRF2-STAT3 axis in LSC-like MA9 cell line using Brusatol, which indeed promoted ferroptosis as indicated by increased lipid ROS, labile iron, reduced pSTAT3, GPX4 protein expression and significantly reduced colony forming units. Moreover, a combination of NRF2-STAT3 inhibitor potentiated the effect of ferroptosis inducers RSL3 and Erastin and enhanced the cytotoxicity in LSCs.
Our scRNAseq analysis of enriched AML LSCs revealed and dissected the mechanistic differences between LSCs and non-LSCs. Our data reveals a potential evasion strategy inherent to LSCs mediated by dependency on labile iron pool to produce suboptimal lipid ROS that supports their survival but prevent ferroptosis by upregulation of NRF2. Our findings suggest that promoting ferroptosis is indeed a promising strategy to combat chemoresistance in AML. Therefore, dual targeting of NRF2-STAT3 along with ferroptosis inducers hold potential as adjuvant therapy by promoting ferroptosis-mediated cell death in AML LSCs
MM-019: Circulating cell-free DNA as a minimally invasive tool for tracking genomic aberrations and treatment response in multiple myeloma: A proof-of-concept study in Indian patients
No full textIntroduction:
Multiple myeloma (MM) is a hematological malignancy marked by uncontrolled plasma cell expansion in the bone marrow (BM). Traditional monitoring via BM aspirate is invasive and may miss tumor heterogeneity. Cell-free DNA (cfDNA) analysis offers a minimally invasive alternative, enabling assessment of comprehensive tumor burden and genomic profiling to improve disease surveillance and treatment evaluation.
Aims :
To optimize cfDNA-based technology for detecting and monitoring genomic aberrations inMMusing targeted next-generation sequencing (NGS) and droplet digital PCR (ddPCR). To identify genomic aberrations influencing therapy response and disease progression, and evaluate cfDNA for monitoring treatment response in MM.
Methods:
Targeted NGS was performed on bone marrow plasma cells (BMPC) from 175 newly diagnosed multiple myeloma (NDMM) samples, with data analyzed using ANNOVAR and the COSMIC database to identify pathogenic mutations. NGS identified trackable baseline mutations in KRAS, NRAS, BRAF, DNAH5, and FAT4 genes across 70 patients. Flow cytometry-based minimal residual disease (MRD) data from 84 follow-up cfDNA samples were analyzed and categorized into four groups according to the total abnormal plasma cells (TAPC) detected. The correlation between cfDNA mutations and MRD positivity or negativity was examined across these four groups.
Results:
Pathogenic mutations were detected in 54% of patients (94/175), with 34% of genes (16/47) harboring mutations. Key mutations: KRAS (20%), NRAS (13%), BRAF (7%), FAT4 (6%), FAT3 (6%), DNAH5 (5%), TP53 (4%), DIS3 (3%), and RB1 (2%). BM mutations were detected in cfDNA for 95% of patients (50/52). The mutation profiles in cfDNA, particularly for KRAS, NRAS, BRAF, DNAH5, and FAT4, correlated with disease kinetics and demonstrated a high concordance (91%) with BM flow cytometry-based MRD detection. We also observed that cfDNA analysis might be more sensitive in detecting MRD in extramedullary disease (EMD) cases, where abnormal plasma cells were absent inBM but mutations were detectable in cfDNA.
Conclusion:
The strong concordance between cfDNA ddPCR analysis and BM flow cytometry-based MRD detection suggests that cfDNA has potential as a complementary tool for disease monitoring. The high prevalence of MAPK pathway mutations highlights keyMMtargets, and cfDNA genomic profiling correlates with clinical outcomes, aiding therapy response prediction
Antimicrobial susceptibility trends of S. Typhi and S. Paratyphi in a post-COVID-19 pandemic India, from a multicenter surveillance network
No full textWe conducted a multicenter surveillance study to identify changes in antimicrobial susceptibility patterns of Salmonella Typhi and S. Paratyphi in India since the COVID-19 pandemic began. We collected S. Typhi and S. Paratyphi isolates from blood or bone marrow culture-confirmed enteric fever cases at eight sites in seven cities across India between 2021 and 2024. We tested the antibiotic susceptibility of 1150 S. Typhi isolates and 265 S. Paratyphi isolates via disc diffusion and determined their minimum inhibitory concentrations (MICs) of ceftriaxone and azithromycin via broth dilution. We identified 18 S. Typhi isolates from Ahmedabad that were resistant to ceftriaxone, indicating a larger emergence of third-generation cephalosporin-resistant S. Typhi in Western India with a novel plasmid profile. Furthermore, we observed yearly increases in the mean, median and 90th percentile of azithromycin MICs for S. Typhi and S. Paratyphi isolates throughout India between 2021 and 2023. Finally, we found that only 0.70% of S. Typhi isolates and 1.13% of S. Paratyphi isolates exhibited susceptibility to ciprofloxacin. Our results indicate the necessity for a shift from ciprofloxacin in the treatment of enteric fever, and the importance of implementing long-term monitoring of resistance to alternative antibiotics such as azithromycin and ceftriaxone
High-Temperature Synthesis of Colloidal CH<sub>3</sub>NH<sub>3</sub>PbBr<sub>3</sub> Perovskite Nanoplatelets and Nanocubes
No full textColloidal CsPbX3 (X: Cl, Br, I) and FAPbX3 (FA: formamidinium) perovskite nanocrystals (NCs) are well explored for their size-, shape-, and surface-dependent optoelectronic properties. However, colloidal MAPbX3 (MA: CH3NH3+, methylammonium) perovskite NCs are relatively less explored, even though MAPbBr3 nanoplatelets were the first halide perovskite NCs reported in the literature. Often, the synthesis temperatures of MAPbBr3 NCs are restricted to ∼65 °C, keeping in mind the thermal instability of the MA precursor solution. Here, we advance the synthesis of MAPbBr3 NCs in a nonpolar medium by increasing the synthesis temperature in the range of 120–160 °C. Colloidal MAPbBr3 nanoplatelets with thicknesses of 1.9 and 2.3 nm are prepared at 120 and 140 °C. It is to be noted that for the nanoplatelets, the molar ratio of MA:Pb is <1, along with a significant contribution from capping organic ligands. Further increases in the synthesis temperature to 160 °C lead to the formation of MAPbBr3 nanocubes with a photoluminescence quantum yield of 70–80%. The temperature-dependent control of the size and shape of colloidal MAPbBr3 NCs results in tuning the quantum confinement of excitons, yielding wavelength-tunable optical properties. This temperature-driven control of the size and shape of MAPbBr3 NCs expands their potential for optoelectronic applications
Impacts of irrigation expansion on moist-heat stress based on IRRMIP results
No full textIrrigation rapidly expanded during the 20th century, affecting climate via water, energy, and biogeochemical changes. Previous assessments of these effects predominantly relied on a single Earth System Model, and therefore suffered from structural model uncertainties. Here we quantify the impacts of historical irrigation expansion on climate by analysing simulation results from six Earth system models participating in the Irrigation Model Intercomparison Project (IRRMIP). Results show that irrigation expansion causes a rapid increase in irrigation water withdrawal, which leads to less frequent 2-meter air temperature heat extremes across heavily irrigated areas (≥4 times less likely). However, due to the irrigation-induced increase in air humidity, the cooling effect of irrigation expansion on moist-heat stress is less pronounced or even reversed, depending on the heat stress metric. In summary, this study indicates that irrigation deployment is not an efficient adaptation measure to escalating human heat stress under climate change, calling for carefully dealing with the increased exposure of local people to moist-heat stress
Polymer-grafted silica based hybrid macrobeads for Pb(II) and Cr(VI) removal from water.
No full textThe presence of heavy metals in water deters its usability for drinking purposes. Indiscriminate disposal of industrial effluent into water bodies further complicates the situation. Accordingly, there is a dire need for a treatment system that can effectively remove the contaminants from water. Although there are solutions like the utilization of membrane and other powder-based adsorbers, challenges like high cost, fouling, scaling, the generation of a new class of waste (post usage), and limited recyclability often limit their usage. Hence, there is a critical need to develop a system that demonstrates high adsorption capacity, is reusable, and is easy to develop. Accordingly, we synthesized silylated polyethyleneimine, grafted it onto silica particles, and tested its efficacy in removing heavy metal contaminants like lead and hexavalent chromium from water. The resultant modified polyethyleneimine modified silica particles (termed as SiEP) outperformed many adsorber materials, including metal–organic framework, zeolite, clay, etc., and it demonstrated a staggering adsorption capacity (Langmuir) of 442 mg/g (pH 6) and 182 mg/g (pH 5) for lead and chromium, respectively at 30 °C. The developed nanopowder was further encapsulated inside polyacrylonitrile macrobeads and tested for its efficacy. Although the encapsulation resulted in a decrease in adsorption capabilities, common problems like high-pressure build-up and inefficient contact associated with powder-based adsorber were avoided upon encapsulation. The macrobeads exhibited 37 mg/g and 20 mg/g adsorption capacities for lead and chromium, respectively. For both the powder and the macrobeads, the adsorption capacity was tested in the presence of mixed ions and both the adsorber demonstrated their unique capability to be selective against targeted ions. They were further tested against a real groundwater matrix synthetically spiked with lead and chromium. Such findings open up a new avenue to developing water treatment materials that demonstrate selectivity and recyclability, indicating their potential for large-scale water treatment applications in industrial settings
Coassembly of enzyme-responsive cholate-conjugated facially amphiphilic polymers.
No full textInspired by the unique self-assembly of bile acid-based facial amphiphiles (FAs), a family of facially amphiphilic cholic acid-derived homopolymers and their coassembled nanoaggregates have been fabricated. The cholate-pendant cationic PC (quaternary amine-based), anionic PA1 (sulfate-based), and PA2 (phosphate-based) polymers individually formed spherical nanoaggregates due to the required hydrophobic/hydrophilic balance. However, the coassembled aggregates of oppositely charged pairs, PC with PA1 or PA2, generated arrays of different nanoaggregates depending on the mixing ratio. Additionally, the polymer–protein–polymer coassembly among two oppositely charged facially amphiphilic polymers and a positively/negatively charged therapeutic protein (lysozyme or insulin) was thoroughly investigated by the UV–vis turbidimetry assay, transmission electron microscopy, and dynamic light scattering. The presence of ester, sulfate, and phosphate groups in PC, PA1, and PA2 makes them susceptible to degradation by esterase, sulfatase, and phosphatase enzymes, respectively. Thus, enzyme-triggered in vitro release of two different therapeutics, small-molecule drugs (doxorubicin, DOX) and biomacromolecules (insulin and lysozyme), has been showcased from the self-assembled and coassembled nanoaggregates in physiological conditions. Overall, the present work successfully demonstrated the development of coassembled nanoaggregates using the two oppositely charged cholate-based FAs, with a promising potential for engineering next-generation enzyme-responsive therapeutic delivery vehicles
Flavylium-containing polymeric probe as encryption ink for reversible sensing of bisulfite ions and formaldehyde.
No full textProlonged absorption of sulfur dioxide (SO2) and formaldehyde (FA) inflicts severe long-term damage to human health. Here we report a fluorescent polymeric probe with flavylium pendants (CP5-FLA) for detecting bisulfite (HSO3–) and FA in an aqueous medium. The probe displays remarkable photophysical characteristics with rapid response times (30/60 s), high sensitivity (detection limit of 1.1/2.6 nM), and the capability for colorimetric and fluorimetric detection for HSO3–/FA. The sensing mechanism is based on the intramolecular charge transfer (ICT) “off-on” process in CP5-FLA tuned by the Michael/reversible Michael addition reactions between the flavyluim groups and HSO3–/FA, as confirmed by electrospray ionization mass spectrometry (ESI-MS) and time-dependent density functional theory (TD-DFT) analysis for the reaction of the model compound toward HSO3– and FA. This work presents a facile approach for developing versatile flavylium-based fluorescent probes through flexible molecular engineering, with potential applications in data encryption
Editorial - A message from the editorial team_2025.
No full textAs we close out another year, it’s time to reflect on our noteworthy progress in 2024. The past year has been particularly exciting, with an increase in submissions, including insightful feature articles, comprehensive reviews, and groundbreaking research from scientists around the globe. The diversity of topics covered not only highlights the vastness of our field but also emphasizes the crucial role polymers play in addressing some of today’s most pressing challenges.
One of the standout features this year has been the strong focus on novelty in both synthesis and application. Polymer science is evolving rapidly, with innovations in material synthesis and processing unlocking new, high-performance materials designed for a wide range of applications. Environmental science and nanomedicine have emerged as key areas of research. The global push for sustainability has led to an increase in studies on biodegradable polymers and materials for environmental cleanup. These advances are critical because, as we develop new polymeric materials, we must also consider their long-term impact on the environment. Polymers are also playing an ever-increasing role in improving human health. From advancing drug delivery systems to enabling breakthroughs in tissue engineering, polymers are revolutionizing the way we treat diseases and manage healthcare. This year’s articles have explored innovative ways to design polymer-based systems that could offer solutions to some of the toughest health challenges. Another exciting development has been the growing focus on polymeric composites for energy technologies. With the rising demand for sustainable energy, polymers are playing an essential in the development of energy storage systems such as batteries, supercapacitors, and fuel cells.
None of this progress would have been possible without the collaborative efforts of our authors, reviewers, and Editorial Advisory Board. The dedication and expertise of all parties have been instrumental in shaping the journal and maintaining high standards. We are also thrilled to announce the launch of an Early Career Editorial Advisory Board. This new initiative will connect with emerging researchers and bring fresh perspectives to the journal, further energizing its dynamic nature. We hope it will encourage innovation and foster meaningful collaborations across generations of scientists. We also look forward to introducing special issues to showcase the active research in polymer science in different countries, as well as highlighting advances in key areas of polymer science.
Looking ahead, we’re committed to continuing to expand the reach and impact of the journal. Our goal is to be a key platform for newcomers and seasoned researchers, helping everyone stay informed on the latest developments in polymer science. We would also like to thank our outgoing Editor-in-Chief Prof. Patrick Theato, who steered the journal to its present success over the past several years. We wish him the very best in his future endeavors. We would also like to thank Ms. Hiromi Uchida, and the publication support team from Taylor and Francis for their constant support with the publication process. Finally, on behalf of the editorial team, we’d like to thank all of our authors, reviewers, and readers; and wish them all the best in 2025. We’re excited for another year of advancements and collaborations that will continue to drive the field of polymer science forward