{"title":"Electrostatic Regulation of Bola-Amphiphilic Peptide Self-Assembly and Nanotube Formation Induced by Salt Ions.","authors":"Danni Li, Yongyi Xu, Yingshan Li, Bin Dai","doi":"10.1021/acsabm.5c00199","DOIUrl":"10.1021/acsabm.5c00199","url":null,"abstract":"<p><p>Peptide self-assembly into nanostructures offers substantial potential for applications in catalysis, drug delivery, and nanodevice fabrication. However, controlling the morphology of these assemblies remains a challenge. In this study, we investigate the role of salt ions in regulating the self-assembly of the bola-amphiphilic peptide KFFFFK, facilitating a transition from twisted fibrils to nanotubes. Using transmission electron microscopy, we show that the addition of NaCl induces the formation of nanotubes, and we detail the time-dependent assembly process. Increased salt concentrations reduce electrostatic repulsion, promoting the lateral merging of fibrils and supporting the formation of closed nanotubes. This phenomenon is also observed with several other salts. These findings underscore the critical role of electrostatic interactions in peptide self-assembly and highlight the importance of salt concentration in directing assembly pathways. Our results provide valuable insights into the mechanisms of peptide self-assembly and offer a versatile approach for designing advanced biomaterials and nanodevices based on well-defined peptide nanostructures.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"4065-4072"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950958","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}
Anusree S Gangadharan, Daniel T Thangadurai, Valarmani M Vasanthakannan, Kittusamy Senthilkumar, Devaraj Nataraj
{"title":"Biopermissible and Hydrophilic G-CNNPs for Noncooperative Binding with Picomolar of Cancer Drug Etoposide and Photodynamic Therapy.","authors":"Anusree S Gangadharan, Daniel T Thangadurai, Valarmani M Vasanthakannan, Kittusamy Senthilkumar, Devaraj Nataraj","doi":"10.1021/acsabm.5c00470","DOIUrl":"10.1021/acsabm.5c00470","url":null,"abstract":"<p><p>Etoposide (ETO), a chemotherapeutic agent for lung cancer, requires precise and prompt detection to optimize cancer management and mitigate toxicity. In this study, we present a scalable solid-state methodology for the synthesis of highly hydrophilic (average contact angle 10.73°) graphitic carbon nitride nanoparticles (g-CNNPs) employing urea and trisodium citrate. The synthesized g-CNNPs possess six surface active sites, enabling their function as effective fluorescence sensors for detecting the lung cancer drug ETO at physiological pH. The g-CNNPs demonstrate high selectivity and sensitivity for ETO detection (Φ<sub>F</sub> 20.29 → 17.95%), with a detection limit (LoD) of 95 pM (<i>R</i><sup>2</sup> = 0.99144), quantification limit (LoQ) of 310 pM, and an association constant (<i>K</i><sub>a</sub>) of 1.0162 M<sup>-1</sup>. The fluorescence quenching of g-CNNPs by ETO is attributed to intermolecular hydrogen bonding, characterized by static quenching and a noncooperative binding mechanism within the g-CNNPs·ETO complex. Additionally, time-correlated single photon counting (TCSPC) analysis confirms the static quenching of g-CNNPs (lifetime 5.175 → 5.281 ns) upon ETO detection. The formation of the g-CNNPs·ETO complex is verified through DFT studies and a range of physicochemical characterization techniques, including XRD, FE-SEM, HR-TEM, XPS, Raman, FT-IR, and UV-vis. The developed detection method proved effective in identifying ETO in urine samples, achieving high recovery rates between 95.45% and 110.78%. To evaluate their biological efficacy, a series of experiments were conducted, including MTT cytotoxicity assays against mouse fibroblast cell lines L929, the anticancer activity of g-CNNPs toward HT29 cells (with and without light exposure), and ROS generation. Collectively, the results from these real samples and biological studies affirm that biopermissible g-CNNPs are promising candidates for clinical trials.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"4351-4366"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951000","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":"Monomer Versus Dimer of Cationic Ir(III) Complexes for Photodynamic Therapy by Two-Photon Activation: A Comparative Study.","authors":"Agoston Barta, Laetitia Vanwonterghem, Matéo Lavaud, Florian Molton, Guillaume Micouin, Anne-Laure Bulin, Akos Banyasz, Jean-Luc Coll, Frédérique Loiseau, Amandine Hurbin, Pierre-Henri Lanoë","doi":"10.1021/acsabm.5c00393","DOIUrl":"10.1021/acsabm.5c00393","url":null,"abstract":"<p><p>Iridium(III) complexes have been recognized as promising candidates for two-photon sensitized photodynamic therapy (PDT). In this context, we report on the study of two complexes: a monomer (<b>IrL</b><sup><b>1</b></sup>) and a dimer (<b>Ir</b><sub><b>2</b></sub><b>L</b><sup><b>2</b></sup>). Both complexes possess 2-phenylpyridine cyclometallating ligands and a pyridylbenzimidazole derivative as an ancillary ligand. In the dimer, the two Ir(III) centers are connected by a non-conjugated bridged bis(pyridylbenzimidazole). We compare the photophysical properties of these complexes. Both display phosphorescent emission in the orange-red part of the visible spectrum, with emissions centered at 610 nm for <b>IrL</b><sup><b>1</b></sup> and 625 nm for <b>Ir</b><sub><b>2</b></sub><b>L</b><sup><b>2</b></sup>, both exhibiting quantum yields of ∼24%. However, <b>Ir</b><sub><b>2</b></sub><b>L</b><sup><b>2</b></sup> proves to be much brighter than the monomer, making the dimer four times brighter than <b>IrL</b><sup><b>1</b></sup>. This trend is consistent under two-photon excitation (TPE), and the singlet oxygen generation quantum yields, with the dimer displaying a figure of merit (σ<sub>TPA</sub> × Φ<sub>Δ</sub>) of 40, compared to only 5 for the monomer. Both complexes generate intracellular ROS and exhibit strong phototoxicity upon blue light activation (λ = 420 nm), achieving submicromolar IC<sub>50</sub> values in HT29 and A549 cell lines after 24 h of incubation. Moreover, with TPE (λ = 800 nm), both complexes also generate intracellular ROS and induce cancer cell death.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"4272-4284"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951013","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}
Natália Cristina Gomes-da-Silva, Alicia de Faria Almeida, Patrícia Severino, Mohammed Al-Qahtani, Luciana Magalhães Rebelo Alencar, Pierre Basílio de Almeida Fechine, Eduardo Ricci-Junior, Laura Fernanda Osmari Vendrame, João Augusto Pereira da Rocha, Solange Binotto Fagan, Ralph Santos-Oliveira
{"title":"Exploring the Anticancer Potential of Lamivudine-Loaded Polymeric Nanoparticles: <i>In Vitro</i> Cytotoxicity, Tissue Deposition, Biochemical Impact <i>In Vivo</i>, and Molecular Simulations Analysis.","authors":"Natália Cristina Gomes-da-Silva, Alicia de Faria Almeida, Patrícia Severino, Mohammed Al-Qahtani, Luciana Magalhães Rebelo Alencar, Pierre Basílio de Almeida Fechine, Eduardo Ricci-Junior, Laura Fernanda Osmari Vendrame, João Augusto Pereira da Rocha, Solange Binotto Fagan, Ralph Santos-Oliveira","doi":"10.1021/acsabm.5c00182","DOIUrl":"https://doi.org/10.1021/acsabm.5c00182","url":null,"abstract":"<p><p>Lamivudine is a synthetic nucleoside analogue to cytosine with a modified sugar moiety. It has potent action against Human Immunodeficiency Virus and chronic hepatitis. Recently, studies have also shown that lamivudine (3TC) can induce apoptosis in cancer cells and inhibit their proliferation, including breast cancer. We prepared polymeric nanoparticles using the double emulsification technique to incorporate polycaprolactone (PCL) as the polymer and lamivudine as the active compound. The nanoparticles were characterized by atomic force microscopy and dynamic light scattering. Then we carried out a full set of <i>in vitro</i> and <i>in vivo</i> analyses, including measurement of cytotoxicity, radiolabeling, biodistribution and biochemistry. The results showed the formation of 273 nm spherical nanoparticles with monodisperse behavior (PDI = 0.052). The radiolabeling with <sup>99m</sup>Tc demonstrated the feasibility of the direct radiolabeling process. The cytotoxicity corroborated the potential against the triple-negative breast cancer line (MDA-MB-231). The biodistribution assay revealed high uptake in the liver, small and large intestines and bladder, besides the presence of nanoparticles in the urine. The <i>in vivo</i> biochemistry analysis showed alterations in some enzyme levels, including: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma GT (GGT), creatinine (CRE), amylase (MAS), lactate dehydrogenase pyruvate (LDH-P) and glucose (GLU). Finally, we performed theoretical studies of molecular docking, molecular dynamics and interactions between lamivudine and key proteins regulating necroptosis, including epidermal growth factor receptor (EGFR), receptor-interacting protein kinase 1 (RIPK1), and receptor-interacting protein kinase 3 (RIPK3). Theoretical results showed lamivudine's adaptability to the binding sites of these proteins, with potential for optimization to enhance hydrophobic interactions and binding affinity. The findings demonstrated the efficacy of lamivudine against breast cancer cells, and the need to better understand the interplay of nanosystems with biochemical parameters.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091963","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}
Benjamin E Campbell, Kori Zhang, Anna Shi, Sabra Rostami, Durante Pioche-Lee, Chen Li, Alexandre Leblond, Alejandro Forigua, Christina-Marie Boghdady, Christopher Moraes, Sasha Cai Lesher-Pérez
{"title":"Integrating Miniaturized Turbines into Microfluidic Droplet Generating Systems for Scalable Microgel Production.","authors":"Benjamin E Campbell, Kori Zhang, Anna Shi, Sabra Rostami, Durante Pioche-Lee, Chen Li, Alexandre Leblond, Alejandro Forigua, Christina-Marie Boghdady, Christopher Moraes, Sasha Cai Lesher-Pérez","doi":"10.1021/acsabm.4c01950","DOIUrl":"10.1021/acsabm.4c01950","url":null,"abstract":"<p><p>Generating microgels is of critical importance in developing granular biomaterials, which have diverse emerging applications in regenerative medicine and tissue engineering. However, producing large volumes of microgels while maintaining a reasonably low population of polydispersity remains a challenge. Here, we introduce the Turbinator, a device that can be added on to the commercially available Shirasu Porous Glass (SPG) microdroplet production system to provide precise control of the local shear stresses around the porous glass droplet production head. In addition to reducing the polydispersity of droplet sizes produced using the SPG, this system allows for continuous production of droplets in inexpensive and massively scalable kerosene oil baths for industrial manufacturing applications. To validate the device, we develop finite element models to understand the local shear stresses applied and characterize the droplets produced under various operating conditions. Finally, we confirmed that this production method supports biological activity via viability and spreading assays of fibroblast cells and invasion assays in a model cancer spheroid system.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"3801-3810"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950664","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":"3D-Printed Scaffold Achieves Synergistic Chemo-Sonodynamic Therapy for Tumorous Bone Defect.","authors":"Cijun Shuai, Zihao Zhang, Min Chen, Bingxin Sun, Xingming Long, Guoyong Wang, Shuping Peng","doi":"10.1021/acsabm.5c00105","DOIUrl":"10.1021/acsabm.5c00105","url":null,"abstract":"<p><p>Various smart scaffolds have recently been developed to address the regeneration of tumor bone defect. However, the recurrence of residual tumor cells poses a serious challenge to postoperative management, highlighting the need for effective therapeutic interventions. In this study, a multifunctional antitumor nanoplatform (Ti<sub>3</sub>C<sub>2</sub>/CuO<sub>2</sub>) for synergistic chemo-sonodynamic tumor therapy was developed and then rationally integrated into a poly(l-lactic acid) (PLLA) scaffold via selective laser sintering. CuO<sub>2</sub> not only releases Cu<sup>2+</sup> ions to facilitate chemodynamic antitumor therapy through the Fenton reaction but also generates H<sub>2</sub>O<sub>2</sub>, which further oxidizes Ti<sub>3</sub>C<sub>2</sub> to produce TiO<sub>2</sub> sonosensitizers. More importantly, the carbon-based substrates after oxidation of Ti<sub>3</sub>C<sub>2</sub> have created favorable conditions for carrier transmission in the sonodynamic process, thereby amplifying the sonodynamic therapy. Additionally, moderate local hyperthermia form periodic sonodynamic therapy produces moderate localized heat therapy to further stimulate bone tissue regeneration. Meanwhile, the sustained release of bioactive ions (such as Cu and Ti ions) from the scaffold also fosters vascularization, further accelerating bone regeneration. This work presents a viable approach to developing multifunctional scaffolds for repairing tumorous bone defects.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"3920-3931"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950683","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":"Robust Janus Hydrogel with Wet-Tissue Adhesive Properties for Wound Dressing and Anti-Postoperative Adhesion.","authors":"Yutong Wang, Weidong Gu, Kunyan Sui","doi":"10.1021/acsabm.5c00118","DOIUrl":"10.1021/acsabm.5c00118","url":null,"abstract":"<p><p>Although adhesive hydrogels have advanced rapidly in recent years, conventional double-sided adhesives still face challenges in achieving effective adhesion to wet tissues and preventing postoperative tissue adhesion. In this study, a novel Janus hydrogel wet adhesive was successfully designed by precisely regulating the distribution of free hydroxyl and phenolic hydroxyl groups on the two surfaces of the hydrogel. The resulting Janus hydrogel exhibits significantly different adhesive and nonadhesive properties on its upper and lower surfaces. Specifically, through a simple boric acid (BA) solution immersion process, BA cross-linked with poly(vinyl alcohol) (PVA) and tannic acid (TA), effectively suppressing the exposure of hydroxyl groups on the upper surface, leading to low adhesion. In contrast, the lower surface retains strong adhesion to various wet tissues, even underwater. Adhesion simulations with pig skin validated the robust adhesion of the hydrogel's bottom surface to wet tissues, while the low-adhesion upper surface effectively prevented tissue adhesion. Furthermore, cytocompatibility, hemolysis, and coagulation tests demonstrated that the PVA/TA/BA hydrogel possesses excellent biocompatibility and notable hemostatic properties. This simple and efficient preparation strategy offers a practical approach for developing novel Janus hydrogels, laying a solid theoretical and practical foundation for their application in wet tissue repair and postoperative antiadhesion treatments.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"3932-3940"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950834","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":"Engineering of Nucleobase-Functionalized Coassembled Hydrogel to Study Cellular Behavior.","authors":"Sourav Bhowmik, Arka Acharyya, Apurba K Das","doi":"10.1021/acsabm.5c00134","DOIUrl":"10.1021/acsabm.5c00134","url":null,"abstract":"<p><p>Hydrogels derived from self-assembling peptides provide considerable benefits in tissue engineering including their biocompatibility and extensive molecular diversity. Short peptides are especially advantageous due to their ease of production, ability to self-assemble, and repeatability. However, their application is currently limited owing to possible toxicity resulting from the chemical modifications required for self-assembly and the coarse gelation conditions. Nucleobase-functionalized derivatives provide an opportunity to use naturally obtained species to minimize cytotoxicity. Therefore, nucleobase-functionalized hydrogels are currently attracting significant interest due to their varied architectures. Herein, we have synthesized a guanine-functionalized alanine derivative and investigated the formation of a coassembled hydrogel with guanosine. The development of the nucleic acid secondary structure within the coassembled hydrogel is studied using circular dichroism and wide-angle powder X-ray diffraction experiments. The thermoreversible nature of the coassembled hydrogel is explored. The biocompatibility of the coassembled hydrogel is evaluated by performing the MTT assay. The coassembled hydrogel is used for cell growth, and 2D cell cultures are carried out on fibroblast McCoy and epithelial A549 cell lines. Live-dead cell imaging is performed by staining with fluorescein diacetate and propidium iodide. The cell proliferation is studied over different time periods using the Alamar Blue assay. Cytoskeletal staining is performed on both cell lines to determine the impact of the coassembled hydrogel on the cells.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"3983-3994"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950903","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":"Calycosin-7-glucoside-Loaded Hydrogel Promotes Wound Healing in Gestational Diabetes Mellitus.","authors":"Jicong Lu, Yingying Guo, Zhaoyuan Yang, Mengxia Xie, Shuangyu Zhang, Keji Li, Jingjing Yang, Shanhui Xue, Da Xu, Kanglu Yan, Yuehua Liu","doi":"10.1021/acsabm.5c00290","DOIUrl":"10.1021/acsabm.5c00290","url":null,"abstract":"<p><p>The prevalence of gestational diabetes mellitus (GDM) is currently on the rise globally, which heightens the risk of adverse pregnancy outcomes and subsequently increases the likelihood of cesarean delivery. GDM can induce hyperglycemic conditions in cesarean wounds, leading to delayed wound healing and complications such as itching, pain, and scarring. These complications significantly impact the quality of life and mental health of mothers. Furthermore, there is a lack of effective clinical prevention strategies. Consequently, the need to improve wound healing after cesarean sections in women with GDM is a pressing concern that warrants our attention. To maximize the therapeutic impact and extend the bioavailability of calycosin-7-glucoside (CG), it was integrated into a hybridized hydrogel (GOHA) as a drug carrier to create the GOHACG hydrogel. Bases on our tests, the GOHACG hydrogel demonstrated a strong capacity for water absorption, appropriate pore size, and good biocompatibility to adjust to the in situ surroundings of the wound. GOHACG also promoted epidermal regeneration, collagen deposition, angiogenesis, and the conversion of macrophages from the M1 to M2 phenotype. Indicating a reduction in the inflammatory response, accelerated wound repair, and minimized skin scarring in a postcesarean delivery model involving gestational diabetic mellitus mice. In brief, the GOHACG possesses significant properties that enhance wound healing in GDM model, suggesting its potential effects in treating wound healing of GDM.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"4186-4199"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950829","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}