{"title":"Recent Advances in Organic Supramolecular Gels: Self-Assembly and Functional Applications","authors":"Mani Rajasekar","doi":"10.1021/acsabm.6c01854","DOIUrl":"10.1021/acsabm.6c01854","url":null,"abstract":"<p>Organic supramolecular gels formed through the self-assembly of π-conjugated molecules such as azobenzenes, coumarins, perylenes, and pyrenes have emerged as versatile materials with diverse functional applications. These gels rely on noncovalent interactions, including hydrogen bonding and π–π stacking, enabling tunable mechanical, optical, and rheological properties. This review explores the self-assembly mechanisms of organic supramolecular gels and their applications in drug delivery, tissue engineering, environmental remediation, and sensing technologies. The relationship between molecular structure and gel performance is critically examined along with recent advancements in enhancing stability and responsiveness. While these materials offer exciting potential, challenges such as mechanical fragility, limited long-term stability, and scalability require further research. Future efforts should focus on designing supramolecular gels with enhanced robustness, biocompatibility, and adaptability to external stimuli. Addressing these limitations will pave the way for next-generation smart materials in biomedical, environmental, and industrial applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 20","pages":"9440–9470"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An NIR-Responsive Theranostic Gutta-Percha for Bacterial Sensing and Photothermal Disinfection during Root Canal Treatment","authors":"Antony Vincy, Jyoti Yadav, Harshita Agarwal, Neha Jain, Raviraj Vankayala","doi":"10.1021/acsabm.6c01903","DOIUrl":"10.1021/acsabm.6c01903","url":null,"abstract":"<p>Root canal treatment (RCT) is the standard endodontic procedure for eliminating infection and preserving natural teeth. However, treatment failure can occur when residual bacteria persist within complex root canal anatomies, as current irrigation protocols do not provide direct confirmation of bacterial presence prior to obturation. Herein, we present SteriGP, an engineered Gutta-Percha (GP)-based proof-of-concept theranostic platform that integrates bacterial detection with localized photothermal disinfection during root canal treatment. SteriGP employs a ferricyanide-mediated bioreaction in which respiration-driven electron transfer from metabolically active bacteria promotes the <em>in situ</em> formation of Prussian blue (PB), providing a visible indicator of bacterial activity. The generated PB exhibits strong near-infrared (NIR) absorption and, upon 808 nm laser irradiation, produces localized hyperthermia for targeted photothermal inactivation of residual bacteria. SteriGP demonstrated concentration-dependent PB formation, photothermal heating, and antibacterial activity against both planktonic and biofilm models of representative Gram-negative (<em>Escherichia coli</em>) and Gram-positive (methicillin-resistant <em>Staphylococcus aureus</em>) bacteria. Furthermore, evaluation in an <em>E. coli</em> biofilm-based resin root canal model demonstrated visible bacterial detection within the canal and effective reduction of bacterial regrowth following NIR irradiation. Collectively, these findings establish the feasibility of integrating bacterial-responsive sensing and localized photothermal therapy into a Gutta-Percha platform for endodontic applications. While additional studies evaluating cytocompatibility, clinically relevant oral pathogens, natural tooth models, and <em>in vivo</em> performance are required, this work provides a foundation for the future development of theranostic biomaterials for precision-guided root canal treatment.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 20","pages":"9972–9982"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Magnetic Nanotransducers as a Universal Platform for Remote Cell Control: Mechanisms, Design, and Therapeutic Potential","authors":"Egor A. Turovsky","doi":"10.1021/acsabm.6c01450","DOIUrl":"10.1021/acsabm.6c01450","url":null,"abstract":"<p>Magnetogenetics represents a new paradigm in biomedicine that employs magnetic nanoparticles (MNPs) as nanotransducers for remote, contactless control of cellular functions <em>in vivo</em> with high spatiotemporal resolution. This review systematically examines three fundamental physical principles underlying magnetogenetics: the magnetomechanical principle, which enables generation of piconewton-scale forces to activate mechanosensitive Piezo1/2 and TRPV4 channels; local “hot-spot” heating, which allows mild activation of thermosensitive TRPV1, TRPA1, and TRPM8 channels without macroscopic tissue temperature elevation; and the principle of magnetically triggered biochemical modulation, encompassing both the controlled release of signaling molecules and the generation of reactive oxygen species (ROS) for remote activation of intracellular cascades. The critical role of nanoparticle physicochemical design—including control over size, shape, doping, and surface functionalization—in achieving target specificity and efficacy is discussed. We review current advances in the application of these approaches to remotely actuated stimulation of cardiomyocytes, cell-specific modulation of neuronal circuits, metabolic regulation, and targeted anticancer therapy, including induction of ferroptosis and modulation of the tumor immune microenvironment. Particular emphasis is placed on key challenges for clinical translation, namely, ensuring specificity of MNP delivery, long-term biosafety of genetic constructs and nanoparticles, standardization of stimulation protocols, and addressing issues of magnetic field penetration depth and focusing precision. By integrating advances in nanotechnology, genetic engineering, and cell biology, magnetogenetics opens new avenues for personalized therapy of neurodegenerative, cardiovascular, and oncological diseases. However, the approach has been subject to significant physical and biological criticism, including fundamental questions regarding the thermodynamic feasibility of nanoscale heating and the mechanical sufficiency of single-particle forces—critiques that temporarily marginalized the field. This review critically examines these controversies and argues that while second-generation systems (e.g., high-moment synthetic nanoparticles and magnetoelectric nanodiscs) have partially alleviated these concerns, rigorous validation and reproducibility remain paramount. Nonetheless, magnetogenetics represents a promising remote alternative to existing methods of cellular modulation.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 20","pages":"9407–9439"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synergistic Electromagnetic and Chemical Enhancement via Carbon Quantum Dot-Functionalized Triangular Silver Nanoplates on Nano-Mica Platelets for Ultrasensitive SERS Biosensing","authors":"Ming-Chang Lu, Pei-Zhen Gao, Yao-Hsuan Tseng, Chih-Chia Cheng, Chung-Feng Jeffrey Kuo, Chih-Wei Chiu","doi":"10.1021/acsabm.6c00690","DOIUrl":"10.1021/acsabm.6c00690","url":null,"abstract":"<p>We report a high-performance ternary nanohybrid for surface-enhanced Raman scattering (SERS) biosensing that integrates sharp-tipped triangular silver nanoplates (TAgNPs) with two-dimensional (2D) exfoliated nano-mica platelets (NMPs) and carbon quantum dots (CQDs). TAgNPs were synthesized via a seed-mediated route and uniformly deposited onto the NMP surface, forming stable TAgNPs/NMPs nanohybrids that enabled a three-dimensional (3D) distribution of electromagnetic hot spots. CQDs were prepared hydrothermally using glucose and reduced glutathione as precursors and subsequently anchored onto the TAgNPs/NMPs surface. This interfacial modification improves energy-level alignment and promotes charge-transfer (CT) contributions, yielding TAgNPs/NMPs/CQDs nanohybrids. For adenine detection, the nanohybrids achieved a limit of detection (LoD) of 10<sup>–9</sup> M and an enhancement factor of 9.3 × 10<sup>8</sup>, with high signal uniformity (relative standard deviation, RSD = 7.4%). For <em>Staphylococcus aureus</em> sensing, the platform reached an LoD of 10 CFU mL<sup>–1</sup> and showed good reproducibility (RSD = 9.2%). Collectively, these results establish a scalable scaffold-stabilization and interface-functionalization co-design strategy for SERS substrates. Exfoliated NMPs act as a programmable 2D support that localizes and stabilizes near-field hot spots, enabling hierarchical 3D architectures. CQDs provide precise interfacial modulation and introduce CT-mediated pathways that enhance molecular capture and signal transduction. The resulting platform supports rapid pathogen screening and offers a generalizable materials blueprint for translational SERS biosensing.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 20","pages":"9491–9502"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Förster Resonance Energy Transfer-Based Selective Detection of Influenza Viruses Using N-Doped Sialic Acid Carbon Dots","authors":"Priyanka Jangra, Manorama Dey, Kunika Lodha, Nagma Parveen","doi":"10.1021/acsabm.6c01240","DOIUrl":"10.1021/acsabm.6c01240","url":null,"abstract":"<p>We report the rational design and synthesis of nitrogen-doped sialic acid-derived carbon dots (SiaMPDA CDs) with excitation-independent green emission and high quantum yield and demonstrate their application as efficient Förster resonance energy transfer (FRET) donors for the selective detection of influenza A virus (IAV) subtypes. The surface functionalization of the CDs with sialic acid moieties enables specific molecular recognition of the viral hemagglutinin (HA) protein via multivalent hydrogen-bonding interactions. In combination with Rhodamine B (RhB) as an acceptor, the SiaMPDA–RhB pair exhibits efficient FRET under native conditions. Upon interaction with IAV (H3N2 and H1N1), the FRET system displays anomalous spectral behavior characterized by a simultaneous increase in both donor and acceptor emission intensities without any spectral shift. Mechanistic investigations suggest the formation of a ternary IAV–SiaMPDA–RhB complex, wherein long-range charge transfer coupled with FRET governs the observed fluorescence response. Control experiments with proteins, membrane vesicles, and liposomes confirm that the signal specificity arises from targeted interactions between the sialic acid functionalities of the CDs and the viral surface proteins. The sensing platform enables selective and sensitive detection of IAV subtypes in the picomolar range, comparable to existing carbon dot-based detection systems. These findings establish N-doped sialic acid carbon dots as promising nanoscale probes for virus detection and provide insights into charge-transfer-coupled FRET mechanisms in complex bionano interfaces.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 20","pages":"9745–9757"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nayanjyoti Kakati, Rahul Deka, Saurabh Dubey, Srijita De, Prathu Raja Parmar, Tanusree Ghoshal, Tamanna Bhuyan, Dipankar Bandyopadhyay
{"title":"Micro-Rheology of an Articular Viscosupplement for Rheumatoid Arthritis","authors":"Nayanjyoti Kakati, Rahul Deka, Saurabh Dubey, Srijita De, Prathu Raja Parmar, Tanusree Ghoshal, Tamanna Bhuyan, Dipankar Bandyopadhyay","doi":"10.1021/acsabm.6c00908","DOIUrl":"10.1021/acsabm.6c00908","url":null,"abstract":"<p>Rheumatoid arthritis (RA) is a widespread joint disease that affects people across a wide range of ages. In RA, the viscoelastic properties of synovial fluid (SF) are significantly compromised, reducing its ability to protect cartilage surfaces during joint movements. Importantly, unlike osteoarthritis, hyaluronic acid (HA) viscosupplements are not effective for the treatment of RA, as they are prone to degradation in the lactic acid environment of RA-affected joints. Therefore, it is crucial to develop viscosupplements that can maintain viscoelastic properties in joints with elevated lactic acid levels. In the present study, we explore the microrheology of mucin-blended HA to maintain viscoelasticity in a simulated RA environment. The study reveals that the mucin-blended hyaluronic acid does not phase separate at higher lactic acid levels and is able to retain the required viscous and elastic behaviors as compared to a pure HA solution. Additionally, a morphological study using atomic force microscopy reveals that the addition of mucin to HA creates a fiber-bundle-like structure, which resists deformation under shear, in contrast to the fiber-like morphologies of pure HA that deform more readily. Furthermore, an interfacial microrheological study using a confocal laser scanning microscope reveals that mucin-blended HA exhibits reduced viscoelastic behavior at the collagen interface compared with pristine HA, suggesting potential boundary lubrication by reducing interactions between HA and the cartilage surface.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 20","pages":"9527–9537"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
André Satoshi Ferreira, Bruna Alves Martins, Giovanna Eller Silva Sousa, Melissa Nishida Hirano, Sabrina Aléssio Camacho, Karina Alves Toledo, Pedro Henrique Benites Aoki
{"title":"Membrane-Associated Phototoxicity of Silica-Coated Gold Nanostars in Colorectal Cancer Cells","authors":"André Satoshi Ferreira, Bruna Alves Martins, Giovanna Eller Silva Sousa, Melissa Nishida Hirano, Sabrina Aléssio Camacho, Karina Alves Toledo, Pedro Henrique Benites Aoki","doi":"10.1021/acsabm.6c01490","DOIUrl":"10.1021/acsabm.6c01490","url":null,"abstract":"<p>Plasmonic gold nanostars are promising photoactivatable platforms for cancer therapy, but their biological performance depends not only on light-to-heat conversion but also on how they interact with cellular interfaces before irradiation. Herein, we investigated silica-coated gold nanostars (AuNS@SiO<sub>2</sub>) as NIR-responsive nanostructures in two colorectal cancer cell models, Caco-2 and HT-29, combining cellular assays with cell-derived Langmuir lipid models. AuNS@SiO<sub>2</sub> exhibited a plasmonic band centered at 810 nm, positive ζ-potential (+32.62 mV), and preserved photothermal activity, reaching 38.56 ± 1.79 °C under 810 nm irradiation, with a temperature increase of 14.71 ± 1.16 °C. In Caco-2 cells, AuNS@SiO<sub>2</sub> showed limited dark toxicity up to 160 μg mL<sup>–1</sup>, with cell viability remaining above 94%, whereas NIR irradiation sharply reduced viability to 14.9 and 4.82% at 267 and 400 μg mL<sup>–1</sup>, respectively. In contrast, HT-29 cells were more sensitive to AuNS@SiO<sub>2</sub> in the absence of irradiation, with viability decreasing to 38.0 and 28.1% at the same concentrations, indicating a stronger contact-associated response. Cell-derived Langmuir lipid models supported this interpretation: at 30 mN m<sup>–1</sup>, AuNS@SiO<sub>2</sub> induced larger relative area expansions in HT-29 models, reaching 34.87 ± 1.04% at the 1:1 ratio, compared with 17.67 ± 1.16% for Caco-2. FTIR analysis showed that nanoparticle interaction mainly affected polar headgroup and interfacial regions, while the lipid acyl-chain region remained largely preserved. Together, these findings indicate that AuNS@SiO<sub>2</sub> elicit cell-line-dependent phototoxic profiles associated with membrane-related interactions, with Caco-2 displaying a predominantly light-amplified response and HT-29 showing a more contact-dominated response.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 20","pages":"9844–9858"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Noninvasive Transdermal Vaccine Platform Using Deep Eutectic Solvents for Cancer Immunotherapy","authors":"Naoaki Fujita, Kiyohiro Toyofuku, Rie Wakabayashi, Yoshirou Kawaguchi, Noriho Kamiya, Masahiro Goto","doi":"10.1021/acsabm.6c00559","DOIUrl":"10.1021/acsabm.6c00559","url":null,"abstract":"<p>Cancer immunotherapy has attracted considerable attention since the early 2010s as an alternative to conventional cancer treatments such as surgery, chemotherapy, and radiotherapy. Among these approaches, cancer vaccines exert preventive and therapeutic effects by eliciting immune responses against tumor antigens. However, most cancer vaccines still rely on injection-based administration, which is associated with pain, the risk of secondary infection, and an increased burden on healthcare professionals. To address these limitations, we focused on noninvasive and convenient transdermal administration of cancer vaccines. Nevertheless, the transdermal delivery of hydrophilic cancer antigen peptides is considered challenging because the stratum corneum, the outermost layer of the skin, acts as a strong barrier against hydrophilic molecules and molecules with molecular weights greater than 500. To overcome this limitation, we developed a deep eutectic solvent (DES)-based formulation for transdermal cancer vaccination. In the present study, an amphiphilic DES composed of choline and oleic acid was prepared. Using this DES, a model cancer antigen peptide (SIINFEKL) was solubilized in an oil-based vehicle, yielding a transdermal formulation. Ex vivo studies demonstrated that the DES-based formulation exhibited greater skin permeation than a phosphate-buffered saline solution and a conventional ionic liquid-based formulation. Optimization with ethanol as a cosolvent yielded an advanced formulation that exhibited even higher skin permeation and showed significant tumor growth suppression in vivo. In addition, transepidermal water loss measurements after administration indicated that the advanced formulation caused little to no skin irritation. DES-based transdermal delivery systems may provide an effective strategy for overcoming the limitations of conventional injectable formulations. To our knowledge, this is the first report describing DES-based vaccine formulation with evaluation of its immunological efficacy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 20","pages":"9478–9490"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149078995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correlating the C-5 Induction Effect on Uracil-Based Nucleoside Lipid Nanoparticles for Enhanced Redox-Mediated Therapeutic Efficacy in Hepatocellular Carcinoma","authors":"Akash Kumar, Srilakshmi V. Patri, Shruthilaya Chilumula, Porkizhi Arjunan, Vasikaran Ayyanar, Pallavi Hanchate, Sandya Rani Bakthavatsalam, Gokulnath Mahalingam, Rama Krishna Kadiyam, Suresh Gadde, Srujan Marepally","doi":"10.1021/acsabm.6c01197","DOIUrl":"10.1021/acsabm.6c01197","url":null,"abstract":"<p>The clinical effectiveness of doxorubicin (DOX) in hepatocellular carcinoma (HCC) remains constrained by poor tumor selectivity and the emergence of multidrug resistance. In this work, we examine how the electronic nature of the C-5 substituent on uracil-based nucleoside lipids shapes the physicochemical and biological behavior of DOX-loaded lipid nanoparticles (LNPs). Four ionizable lipids were designed, combining either thymidine (methyl, electron-donating) or 5-fluorouridine (FURD; fluorine, electron-withdrawing) head groups with α-tocopherol or cholesterol tails through a triazole linker, and synthesized via copper-catalyzed azide–alkyne cycloaddition, followed by formulation into DOX-LNPs. Notably, introducing the electron-withdrawing fluorine in FURD-based LNPs led to a clear improvement in DOX encapsulation efficiency (72–76% compared to 52–56%), enhanced pH-responsive drug release, and increased intracellular reactive oxygen species generation in HepG-2, Huh-7, and SK-Hep-1 cells. This redox perturbation triggers mitochondrial membrane depolarization, elevates Bax/Bcl-2 ratios, enhances cytochrome <em>c</em> release and caspase-3 cleavage, and induces pronounced S-phase arrest and apoptosis. Confocal microscopy further revealed markedly enhanced nuclear accumulation of DOX in the case of FURD-LNPs, while in vivo biodistribution studies showed clear preferential uptake in the liver. Density functional theory (DFT) calculations revealed distinct modulation of the frontier molecular orbital energy gap (<em>E</em><sub>HOMO</sub><sub>–</sub><sub>LUMO</sub>) between the substituents, providing a theoretical electronic rationale that strongly correlates with these empirical trends. Taken together, these findings suggest an important correlation between head-group inductive modulation and redox-driven anticancer activity, offering a promising molecular design strategy for nucleoside–lipid nanocarriers in HCC therapy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 20","pages":"9683–9700"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rationale Design of a Liposomal Formulated Phenanthro[9, 10-d]imidazole-Based ZnII Complex as a Targeted Anticancer Unit","authors":"Mallayasamy Siva, Anushree Lye, Debojit Talukdar, Nanjundan Raghul, Atanu Barik, Adele Stewart, Gaurav Das, Biswanath Maity, Priyadip Das","doi":"10.1021/acsabm.6c01217","DOIUrl":"10.1021/acsabm.6c01217","url":null,"abstract":"<p>The development of targeted and multifunctional anticancer nanoplatforms remains challenging due to limited selectivity, systemic toxicity, drug resistance, and off-target effects associated with conventional platinum-based chemotherapy. Zn(II) complexes have emerged as promising low-toxicity metal-based alternatives, exhibiting enhanced cytotoxicity toward cancer cells compared to healthy cells. In this study, a Schiff base ligand (<strong>K</strong>) was synthesized via condensation of 4-(1<em>H</em>-phenanthro[9,10-d]imidazol-2-yl)aniline and salicylaldehyde followed by complexation with Zn(II) to form a Zn(II) complex (<strong>S1</strong>). To enhance site-specific cellular uptake, Zn(II) complex <strong>S1</strong> was encapsulated within folic acid-functionalized 10,12-pentacosadiynoic acid (FA-PCDA) and 1,2-dimyristoyl-<em>sn</em>-glycero-3-phosphocholine (DMPC)-based liposomes via molecular co-assembly, significantly improving stability and targeting capability. The resulting liposomal formulation of Zn(II) complex <strong>S1</strong> (<strong>Lip-S1</strong>) exhibited characteristic fluorescence properties, enabling potential imaging applications. <strong>Lip-S1</strong> selectively targeted folate receptor-expressing cervical cancer (HeLa) cells, demonstrating enhanced anticancer efficacy with a half maximal inhibitory concentration (IC<sub>50</sub>) of 143.8 μg mL<sup>–1</sup> compared to free <strong>S1</strong> and bare liposomes. Functional assays revealed that <strong>Lip-S1</strong> inhibited cell proliferation, migration, and tumor spheroid growth while inducing apoptosis through mitochondrial membrane depolarization, elevated intracellular reactive oxygen species (ROS), caspase 3/7 activation, and modulation of apoptotic proteins (Bax upregulation, Bcl-2 downregulation). ROS scavenging studies confirmed that apoptosis is primarily mediated by oxidative stress linked to the PI3K/AKT (phosphatidylinositol 3 kinase/protein kinase B) signaling pathway. Enhanced cellular internalization of <strong>Lip-S1</strong> relative to controls was also observed. These results highlight <strong>Lip-S1</strong> as a targeted, fluorescence-trackable nanoplatform for ROS-mediated anticancer therapy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 20","pages":"9701–9716"},"PeriodicalIF":5.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}