Search Results (162)

Unsaturated polyester resins (UPRs) represent challenging systems for reversible-deactivation radical polymerization (RDRP) because chain propagation, branching, and localized gelation may occur concurrently. This study systematically investigates the influence of the concentration of the RAFT agent 2-cyano-2-propyl dodecyl trithiocarbonate (CPDT), the chemical structure of the polyester prepolymer, and the nature of the acidic comonomer on the structural evolution of RAFT-modified unsaturated polyester copolymers. Three copolymer series synthesized at different CPDT concentrations were investigated: p-EGM:AA:[CPDT], p-EGM:MAA:[CPDT], and p-PGM:MAA:[CPDT]. Structural changes were characterized using H NMR, H–H COSY, UV–Vis spectroscopy, and gel permeation chromatography (GPC). Semi-quantitative analysis of normalized H NMR integral intensities was performed using Relative Vinyl Intensity (RVI), CPDT-associated methyl intensity (MI*), and normalized aliphatic intensity (AI*) to compare changes in selected proton environments among the investigated copolymer series. Increasing CPDT concentration was accompanied by a decrease in the normalized residual maleate vinyl signal, although the magnitude of this change depended strongly on copolymer composition. The most pronounced decrease in RVI was observed for the p-EGM:AA:[CPDT] series, from 0.6291 to 0.0528, whereas substantially smaller changes were observed for the p-EGM:MAA:[CPDT] series. The MI* and AI* profiles exhibited composition-dependent variations, reflecting changes in the relative contributions of CPDT-associated methyl and overlapping aliphatic proton environments, respectively. Because the aliphatic region used for AI* contains overlapping polymer- and CPDT-derived contributions, AI* is not interpreted as a quantitative measure of polymer-backbone branching. Overall, the combined NMR and GPC/SEC results reveal composition-dependent structural changes accompanying RAFT copolymerization and demonstrate that both the polyester matrix and the acidic comonomer influence the response of these heterogeneous unsaturated polyester systems to variations in CPDT concentration. Full article

A biological/synthetic hybrid graft copolymer was obtained by grafting poly(acrylic acid) (PAA, synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization) to amylopectin (AMP). The novel graft copolymer presents amphiphilic properties due to the inherent insolubility of AMP in water and was further utilized as a mediator for the synthesis of gold nanoparticles (AuNPs) following an environmentally friendly in situ procedure. The AMP-g-PAA copolymer formation by the interaction of the PAA end groups with the C(6)-OH groups on an AMP backbone was confirmed by Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) and 1D (proton (¹H NMR) and carbon (¹³C NMR) nuclear magnetic resonance, and Distortionless Enhancement by Polarization Transfer (DEPT)) and 2D (correlation (COSY) and heteronuclear single quantum coherence (HSQC)) spectroscopies. The calculated degree of substitution of 1.17 suggests that the grafting was done at one OH from the three in an anhydroglycosidic unit (AGU) (preferably at that in C6 position), with a mean grafting efficiency of 76%. Additional information obtained using thermogravimetric analysis shows that the thermal decomposition of AMP-g-PAA occurs in two steps, with a residual mass of ~16 wt% at 700 °C, higher than AMP or PAA, indicating increased thermal stability of the copolymer. Dynamic and electrophoretic light scattering (DLS and ELS) measurements were used to determine the hydrodynamic size and ionic charge of the AMP-g-PAA self-assemblies in aqueous solution as well as their stability. The AMP-g-PAA was subsequently tested as a reducing agent in the environmentally friendly synthesis of AuNPs in aqueous solution, at different incubation temperatures, reaction duration, and inorganic/polymer weight ratios. The development of the surface plasmon resonance band of AuNPs, observed in UV–vis spectra, was consistently monitored over the reaction time. DLS analysis indicated time-dependent changes in the AuNPs’ particle size distributions, while scanning transmission electron microscopy confirmed that the AuNPs formed at the inorganic/polymer weight ratio of 0.36 and at 60 °C were predominantly well-dispersed, spherical-shaped nanoparticles. The AuNPs synthesized in situ within the copolymer matrix did not introduce additional cytotoxicity compared to the parent copolymer alone, with the composites representing a promising safety baseline for further investigation in biomedical applications. Full article

The effect of reversible addition–fragmentation chain transfer (RAFT) polymerization on the structure, morphology, and thermal degradation behavior of polypropylene glycol maleate–acrylic acid copolymers (p-PGM:AA) was investigated using 2-cyano-2-propyl dodecyl trithiocarbonate (CPDT) as the RAFT agent. Copolymers synthesized at different CPDT concentrations were characterized by ¹H/¹³C NMR spectroscopy, gel permeation chromatography (GPC), transmission electron microscopy (TEM), thermogravimetric analysis coupled with mass spectrometry (TG–MS), isoconversional kinetic methods, and density functional theory (DFT) calculations. ¹H NMR spectroscopy revealed a progressive decrease in the relative intensity of vinyl proton signals with increasing CPDT concentration, indicating enhanced conversion of unsaturated fragments during copolymerization. Alkaline hydrolysis followed by ¹H NMR and GPC analysis of the degradation products confirmed cleavage of polyester segments and yielded low-molecular-weight fragments with M_n = 1370 g mol⁻¹ and narrow dispersity (Đ = 1.035), providing additional information on the architecture of the vinyl-polymerized segments. Increasing CPDT concentration resulted in lower molecular weights and narrower molecular weight distributions of the soluble copolymer fractions. TEM analysis demonstrated broader domain size distributions and increased morphological heterogeneity in RAFT-modified samples, accompanied by an increase in swelling degree. Thermogravimetric analysis showed that RAFT-modified systems undergo multi-stage thermal degradation with the appearance of an additional low-temperature stage associated with thermolabile fragments. TG–MS revealed earlier evolution of CO₂ and oxygen-containing species and changes in the distribution of volatile products. DFT calculations indicated a decrease in the HOMO–LUMO energy gap and suggested the participation of RAFT-derived fragments in the energetic characteristics of decarboxylation processes. Isoconversional and nonlinear kinetic analyses demonstrated increased kinetic heterogeneity for branched copolymer s synthesized at elevated CPDT concentrations, whereas cross-linked systems exhibited more uniform degradation behavior. The combined experimental and theoretical results demonstrate that RAFT polymerization provides an effective route for tuning the macromolecular architecture, morphology, and thermal degradation pathways of p-PGM:AA copolymers. Full article

Despite its established role as a cornerstone of chemotherapy for solid tumors, 5-Fluorouracil (5-FU) clinical efficacy remains limited by chemoresistance and heterogeneous drug response. Traditional explanations have focused on intracellular metabolism and genetic determinants; however, increasing evidence identifies the plasma membrane as a critical regulatory interface controlling drug availability, signaling integration, and cell fate. Here, we propose a membrane-centered framework in which compartmentalized cAMP/PKA signaling, modulated by repurposed vasoregulatory agents—levosimendan, milrinone, and terbutaline—enhances 5-FU response by functionally remodeling the cancer cell membrane. This remodeling may influence lipid raft organization, ENT1/SLC29A1 transporter trafficking, and the balance between drug influx and efflux, increasing intracellular 5-FU bioavailability and overcoming membrane-mediated pseudo-resistance. In parallel, cAMP-dependent signaling may modulate redox homeostasis, mitochondria-associated membranes, and apoptotic threshold regulation, shifting the cellular response toward irreversible cell death. Importantly, this framework is reconciled with canonical resistance mechanisms—including TYMS upregulation, DPD overexpression, and MMR deficiency—positioning membrane phenotype as a functionally upstream regulatory layer. Differential sensitivity observed experimentally in bladder versus prostate cancer models supports the concept of integrated membrane phenotype biomarkers. Clinical translation requires rigorous pharmacokinetic–pharmacodynamic validation and cardiovascular safety assessment. Redefining the plasma membrane as a dynamic therapeutic interface may provide a rationale for drug repurposing, patient stratification, and personalized combination strategies. Full article

Background/Objectives: Patients with relapsed/refractory multiple myeloma (RRMM) have poor survival outcomes and limited treatment options. The increasing utilization of multiagent therapies for earlier lines of treatment and novel drug classes including BCMA-targeting agents in subsequent lines of therapy has created a need for innovative treatment platforms in patients who have relapsed after or are refractory to these current standard-of-care approaches. Iopofosine I 131 is a ¹³¹iodide (¹³¹I)–phospholipid conjugate that exploits the selective uptake and retention of phospholipid ethers through lipid rafts to facilitate tumor delivery of ¹³¹I. Methods: The objective of this phase 1 dose-escalation study was to assess the safety and tolerability of single and fractionated dose schedules of iopofosine I 131 + low-dose dexamethasone in heavily pretreated patients with RRMM. Results: The most common AEs overall were cytopenias, notably thrombocytopenia (93.5%), lymphopenia (74.2%), anemia (71%), leukopenia (61.3%), and neutropenia (58.1%). All patients experiencing hematologic adverse events recovered from those events with median time of recovery 21 days post-nadir. Nonhematologic adverse events were mostly limited to Grade 1 and 2. Dose-limiting toxicities included four Grade 4 thrombocytopenia events lasting longer than 7 days, one Grade 4 neutropenia, and one Grade 3 insomnia. The DMC determined 31.25 mCi/m² was the maximum tolerated dose in the single-dose group, and 20 mCi/m² × 2 doses was the maximum tolerated dose in the fractionated-dose group. For patients monitored through 85 days following the first infusion, 22 of 26 (84.6%) achieved stable disease after treatment, and 4 of 26 (15.4%) achieved a partial response. Conclusions: A favorable safety and tolerability profile and preliminary clinical activity support further development of iopofosine I 131 in RRMM. Full article

Fatty liver disease represents a major metabolic disorder affecting domestic animals worldwide, with significant implications for animal health, welfare, and agricultural productivity. Disrupted communication between mitochondria and other organelles—particularly the endoplasmic reticulum, lipid droplets, and lysosomes—plays a critical role in disease pathogenesis. This review synthesizes knowledge on inter-organellar communication across domestic animals, with emphasis on species-specific adaptations. We address the “Dairy Cow Paradox”—periparturient dairy cows develop severe hepatic steatosis (>30% liver fat), yet under sterile conditions, they have a higher threshold for progressing to sterile steatohepatitis compared to rodents and humans. However, it is critical to note that severe fatty liver in dairy cows is indeed associated with impaired autophagy, inflammation, and liver damage, particularly when accompanied by ketosis or concurrent infections, and 39% of transition cows exhibit moderate to severe lymphocytic hepatitis. We propose that the tolerance to severe steatosis in dairy cows arises from three adaptations: (1) attenuated innate immune sensing via the cGAS-STING pathway; (2) enhanced lipid buffering from perilipin 5 (PLIN5) with a hypothesized ruminant-specific Val152 substitution that may stabilize lipid droplet–mitochondria contacts; and (3) dampened calcium signaling due to ER–mitochondria membrane lipid raft rigidity, elevated inositol 1,4,5-trisphosphate receptor 2 (IP₃R2) expression, and reduced mitochondrial calcium uniporter (MCU) conductance. We contrast this with the inflammatory steatohepatitis common in rodent models driven by calcium overload and mitochondrial DNA (mtDNA) release, and glucocorticoid-mediated mitofusin 1 (MFN1) suppression, causing mitochondrial fragmentation in poultry. We identify critical knowledge gaps, including the need to define bovine and avian mitochondria-associated endoplasmic reticulum membrane (MAM) proteomes and spatially resolve hepatic zonal communication patterns. Targeting organellar communication hubs with nutraceuticals or pharmacological agents offers promising therapeutic strategies. Full article

Multifunctional scaffolds that combine structural support with the controlled delivery of bioactive agents remain a major challenge in tissue engineering. To extend the use of these devices in biomedicine, 3D printing is presented as an alternative that enables the manufacture of complex devices tailored to each patient, thereby solving specific problems in a timely and efficient manner. In this study, porous 3D scaffolds were fabricated via digital light processing (DLP) using a PET-RAFT resin composed of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and poly(ethylene glycol) diacrylate (PEGDA₅₇₅). Sodium chloride (NaCl) was incorporated as a porogen, while insulin-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were embedded as osteoinductive agents. The printed constructs exhibited high-resolution, reproducible trabecular-like architectures, as confirmed by micro-computed tomography (micro-CT), with interconnected pores averaging 70.7 ± 24.7 μm and a total porosity of 57.0 ± 6.98%. Thermal and chemical analyses confirmed scaffold stability and controlled degradability. Cytocompatibility assays using MC3T3-E1, C2C12, hGMSCs, and C166-GFP cells showed viability above 80% after 7 days (ISO 10993-5). Insulin-loaded nanoparticles enabled sustained release, characterized by an initial burst followed by gradual release up to 72 h. Dynamic bioreactor culture enhanced cell adhesion and RUNX2 expression, confirming the osteoinductive potential of the hybrid scaffold for advanced BTE applications. This study introduces an innovative PET-RAFT-derived resin that combines structural reinforcement with spatiotemporal regulation of insulin release, offering a potential strategy for enhanced biomaterial tissue engineering and tailored therapeutic interventions. Full article

Background/Objectives: Giardia lamblia is an intestinal protozoan responsible for giardiasis, a globally prevalent parasitic disease. Current therapeutic options, including nitroimidazoles and benzimidazoles, have increasing treatment failures due to resistance, adverse reactions, and patient non-compliance. Drug repositioning offers a cost-effective strategy for identifying new antigiardial agents. This study aimed to evaluate the in vitro antiparasitic effects and possible mechanisms of action of the tricyclic antidepressant imipramine against G. lamblia trophozoites. Methods: Trophozoites were exposed to increasing concentrations of imipramine (25–125 µM). Growth inhibition and adhesion capacity were quantified using cell counts. Apoptosis- or necrosis-like death was evaluated through Annexin V/PI staining. The expression and distribution of α-tubulin and lipid rafts were analyzed by immunofluorescence microscopy. Finally, the effect of the drug on encystment efficiency was assessed in vitro. Results: Imipramine inhibited G. lamblia trophozoite growth in a concentration-dependent manner, with an IC₅₀ of 42.31 µM at 48 h. The drug significantly reduced adhesion capacity (>90% at 125 µM) and induced apoptosis-like cell death, as evidenced by Annexin V positivity. Immunofluorescence revealed disruption of α-tubulin distribution and lipid raft organization, accompanied by morphological rounding. Moreover, encystment efficiency decreased in a concentration-dependent mode, suggesting interference in the differentiation process. Conclusions: This investigation describes, for the first time, the antigiardial potential of imipramine, which alters cytoskeletal organization, membrane microdomains, and differentiation pathways, ultimately leading to apoptosis-like cell death. These findings position this compound as a promising lead structure and support further exploration of tricyclic antidepressants as scaffolds for the development and optimization of new antiparasitic agents, as well as future studies on their molecular targets and in vivo efficacy. Full article

This study investigated real-time polymerisation kinetics and mechanical properties under accelerated ageing of novel universal bulk-fill composites incorporating reversible addition–fragmentation chain transfer (RAFT) agent ß-allyl sulfone, designed for anterior and posterior applications. Five bulk-fill composites were tested: Tetric Plus Fill and Tetric Plus Flow (new universal composites); their predecessors, Tetric PowerFill and Tetric PowerFlow (Ivoclar); and RAFT-free Ecosite Bulk Fill (DMG). Specimens were polymerised for 3 s (~3000 mW/cm²), 10 s (~1200 mW/cm²), or 20 s (~1200 mW/cm²). Degree of conversion (DC) was monitored during and after curing, with mechanical testing after 24 h and after thermal cycling. DC and maximum polymerisation rate at 4 mm depth were significantly lower than at 0.1 mm for all materials and curing times. Three-second curing accelerated the polymerisation rate at both depths. Except for Ecosite cured for 3 or 10 s as RAFT-free material, DC ratios at 4 mm exceeded 80% of surface values. Tetric Plus Fill and Ecosite exhibited the highest flexural strength after 24 h, while PowerFill and Ecosite showed the highest flexural modulus at 24 h and after thermal cycling. Rapid curing did not compromise mechanical properties after 24 h, except for PowerFlow, the composite with the lowest filler vol%, but negatively affected both flowable composites after ageing. Thermal cycling reduced flexural strength in most tested conditions, but all materials and curing conditions more than satisfied the ISO 4049 requirements. The new simplified universal composite Plus Fill has a higher DC and improved polymerisation kinetics compared to its predecessor, PowerFill. Rapid curing is not recommended for the material without RAFT agents. Full article

Nanogels provide unique opportunities for stabilizing fragile enzymes through soft, hydrated polymer networks. Here, we report the development of a glutathione peroxidase (GPx)-loaded nanogel (GPxNG) engineered via a mild “grafting-to” epoxy–amine coupling strategy to enhance enzyme stability and antioxidant function. An amphiphilic copolymer composed of methacrylated 2,2,6,6-tetramethyl-4-piperidyl (PMA) and glycidyl methacrylate (GMA) was synthesized by controlled reversible addition–fragmentation chain-transfer (RAFT) polymerization using a poly(ethylene glycol) (PEG) macro-chain transfer agent (macro-CTA), yielding well-defined polymer chains with reactive epoxy groups. Covalent conjugation between polymer epoxides and GPx enzyme surface amines generated soft, PEGylated nanogels with high coupling efficiency, uniform particle sizes, and excellent colloidal stability. The engineered nanogels exhibited shear-thinning injectability, robust storage stability, and non-cytotoxic behavior in RAW 264.7 macrophages. Compared with native GPx enzyme, GPxNGs demonstrated significantly enhanced reactive oxygen species (ROS) scavenging activity, including strong inhibition of lipid peroxidation and copper-induced low-density lipoprotein (LDL) oxidation. Importantly, the nanogels preserved GPx enzyme activity after extended storage, freeze–thaw cycles, and repeated catalytic use, whereas the free enzyme rapidly lost function. This protective effect arises from the nanoscale confinement of the GPx enzyme within the flexible PEG-based network, which limits unfolding and aggregation. Overall, this work introduces a simple and biocompatible “grafting-to” nanogel platform capable of stabilizing redox-active enzymes without harsh conditions. The GPx nanogels combine high enzymatic preservation, potent antioxidant activity, and excellent handling properties, highlighting their potential as a therapeutic nanoplatform for mitigating oxidative stress-associated disorders such as atherosclerosis. Full article

Background/Objectives: Atorvastatin, a lipophilic HMG-CoA reductase inhibitor used for lipid lowering, also exhibits considerable anti-neoplastic activity. Although previous studies have shown that glucose starvation can potentiate several anticancer chemotherapies, atorvastatin has not been rigorously investigated for its impact on metabolic vulnerabilities and the effects on cholesterol-rich lipid rafts in aggressive tumors. This work aims to evaluate the combined anticancer activity of atorvastatin with metabolic interventions, specifically glucose starvation, on U-87 (glioblastoma) and MDA-MB-231 (triple-negative breast cancer) cell lines. Methods: U-87 and MDA-MB-231 cancer cells were cultured in either normal or glucose-free media and treated with different concentrations of atorvastatin. The impact of atorvastatin on these cancer cells was analyzed by examining cell viability, apoptosis, cell cycle, and changes in membrane order within lipid rafts. Results: This study found that glucose starvation increased the sensitivity of U-87 cells to atorvastatin by lowering IC₅₀ values and eliciting arrest in the G1 phase of the cell cycle. MDA-MB-231 cells were less dependent on glucose for viability; however, atorvastatin consistently induced S-phase arrest across both metabolic states. Additionally, atorvastatin induced apoptosis in both U-87 and MDA-MB-231 cells, with the effect being more pronounced and dose-dependent in the fasting state with glucose. Interestingly, both Caspase-3 and Caspase-9 were consistently downregulated by atorvastatin in U-87 cells, regardless of the fasting state, corresponding to the induction of cell cycle arrest. Membrane lipid rafts exhibited decreased membrane order under glucose starvation, which was further decreased in response to atorvastatin in both cell lines, indicating a reduction in cholesterol. Conclusions: These results demonstrate that atorvastatin exhibits anticancer activity, characterized by both contextual and metabolic targeted effects, including a reduction in cancer proliferation, the triggering of cell cycle arrest via the downregulation of caspase pathways, and a decrease in membrane order. Notably, the combined activity of combining antilipemic agents with glucose-fasting provides potential metabolic strategies that could help create more effective and personalized approaches to cancer treatment. Full article

Herein, we report a combined computational and experimental investigation into the recently reported universal pyrazole-based reversible addition-fragmentation chain transfer (RAFT) agents (Z−C(=S)−S−R, where Z is 3,5-dimethyl-1H-pyrazol-1-yl), which can mediate controlled radical polymerization of a broad scope of monomers without the need for an additional initiator or catalyst. The results reveal that the high molar absorption coefficient and efficient photolysis kinetics of pyrazole-based chain transfer agents (CTAs) under blue light (${\lambda }_{\max }$ = 465 nm) enable rapid radical generation, underpinning ultrafast polymerization of acrylates, acrylamides, methacrylates, and N-vinylpyrrolidone (NVP). While the efficient light absorption is attributed to structural dissimilarity between the Z group and the S–R group (which breaks the local symmetry of the C=S group), the fast photolysis originates from favorable $\pi$ electron donation from the Z group to the C=S group. Meanwhile, the $\pi$ electron donation is still weaker than in xanthates, which explains the excellent control of a wide range of monomers, except methacrylates. This work establishes design principles for next-generation CTAs for ultrafast and monomer-universal photoiniferter RAFT polymerization. Full article

Novel amphiphilic block copolymers of N-vinyl pyrrolidone (NVP) and either n-hexyl methacrylate (HMA, PNVP-b-PHMA) or stearyl methacrylate (SMA, PNVP-b-PSMA) were prepared by RAFT polymerization techniques and the sequential addition of monomers starting from the polymerization of NVP and using two different Chain Transfer Agents, CTAs. PNVP-b-PHMA are amorphous block copolymers containing constituent blocks with both high and low Tg values, whereas PNVP-b-PSMA are amorphous–semi-crystalline copolymers. Samples with different molecular weights and compositions were obtained. The copolymers were microphase-separated, but partial mixing was also observed. The presence of the amorphous PNVP block reduced the crystallinity of the PSMA blocks in the PNVP-b-PSMA copolymers. The thermal stability of the blocks was influenced by both constituents. The self-assembly behavior in THF, which is a selective solvent for polymethacrylate blocks, and in aqueous solutions, where PNVP was soluble, was examined. Unimolecular or low-aggregation-number micelles were obtained in THF for both types of samples. On the contrary, high-aggregation-number, spherical, and compact micelles were revealed in aqueous solutions. The increase in the steric hindrance of the side ester group of the polymethacrylate chain led to slightly lower degrees of association. The hydrophobic compound curcumin was efficiently encapsulated within the micellar core of the supramolecular structures in aqueous solutions. Micelles with higher aggregation numbers were more efficient in the encapsulation of curcumin. The results of this study were compared with those obtained from other block copolymers based on PNVP. Full article

A significant challenge in cancer treatment is the rising problem of drug resistance that reduces the effectiveness of therapeutic strategies. Current knowledge shows that multiple mechanisms play a role in cancer drug resistance. Another mechanism that has gained attention is the alteration in sphingolipid trafficking and the dysregulation of its metabolism, which was reported to cause cancer-associated drug resistance. Sphingolipids are lipids containing sphingosine and have multiple roles, ranging from lipid raft formation, apoptosis, and cell signaling to immune cell trafficking. Recent studies show that in developing cancer cells, altered or dysregulated sphingolipids are associated with drug efflux and promote the survival of cancer cells by bypassing apoptosis. Upregulated levels of the glucosylceramide synthase (GCS), an enzyme that functions in sphingolipid metabolism, lead to the upregulated ABCB1 gene that induces drug efflux from the cancer cells. These bypass mechanisms make drugs that induce apoptosis in tumor cells ineffective. By highlighting the current findings, this review aims to provide a mechanism of drug resistance caused by the dysregulation of glucosylceramide synthase, sphingosine kinase, and acid ceramidase enzymes as possible therapeutic targets to enhance the effectiveness of the currently used chemotherapeutic agents. Full article

In this study, novel triblock copolymers, including poly(N-isopropylacrylamide)-block-poly(ε-caprolactone)-block-poly(N-isopropylacrylamide) (PNIPAM-b-PCL-b-PNIPAM), poly(N-vinyl-pyrrolidone)-block-poly(ε-caprolactone)-block-poly(N-vinyl-pyrrolidone) (PNVP-b-PCL-b-PNVP), poly(N-isopropylacrylamide-co-N,N-dimethylaminoethyl methacrylate)-block-poly(ε-caprolactone)-block-poly(N-isopropylacrylamide-co-N,N-dimethylaminoethyl methacrylate) (P(DMAEMA-co-NIPAM)-b-PCL-b-P(NIPAM-co-DMAEMA)), and poly(N,N-dimethylacrylamide)-block-poly(ε-caprolactone)-block-poly(N,N-dimethylacrylamide) (PDMA-b-PCL-b-PDMA), were synthesized via a combination of ring-opening polymerization (ROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization. The synthesis was performed using novel bifunctional PCL-based RAFT macro chain transfer agents (macroCTAs; MXTPCL-X1 and MXTPCL-X2) with a m-xylene-bis(2-mercaptoethyloxy) core. Initially, m-xylene-bis(1-hydroxy-3-thia-propane) (MXTOH), which has not previously been used in lactone polymerization, was synthesized via the reaction of α,α′-dibromo-m-xylene with 2-mercaptoethanol in the presence of sodium in ethanol. Subsequently, Sn(Oct)₂-catalyzed ROP of ε-caprolactone (ε-CL) using MXTOH as an initiator yielded PCL-diol (MXTPCLOH). The resulting PCL-diol underwent further functionalization through esterification and substitution reactions, leading to the formation of PCL-based RAFT macroCTAs. Triblock copolymers were synthesized using these macroCTAs with AIBN as an initiator. The synthesized products, along with their intermediates, were characterized using FTIR and ¹H NMR spectroscopy. The number average molecular weight (M_n) and polydispersity index (Ð) of PCL-based macroCTAs were determined by using GPC analysis. The sensor capabilities of the synthesized novel triblock copolymers were investigated on the determination of syringic acid and it was determined that the most sensitive polymer was PNVP-b-PCL-b-PNVP (MXTP2). The working range was between 1.5 µg/mL and 15 µg/mL and the limit of detection (LOD) was found to be 0.44 µg/mL using DPV on MXTP2 polymer sensor. Full article