Cody S. Madsen, Ashley V. Makela, Chima V. Maduka, Emily M. Greeson, Anthony Tundo, Evran Ural, Satyajit Hari Kulkarni, Ahmed A. Zarea, Matti Kiupel, Maryam Sayadi and Christopher H. Contag*,
{"title":"","authors":"Cody S. Madsen, Ashley V. Makela, Chima V. Maduka, Emily M. Greeson, Anthony Tundo, Evran Ural, Satyajit Hari Kulkarni, Ahmed A. Zarea, Matti Kiupel, Maryam Sayadi and Christopher H. Contag*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsabm.5c00590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luis M Negrón, Edwin Vázquez-Rosa, Luxene Belfleur, Tanya L Díaz, Bismark Madera-Soto, Irving E Vega, José M Rivera
{"title":"Guanosine-Based Supramolecular Particles for Enhanced Drug and Gene Delivery in Cell Culture.","authors":"Luis M Negrón, Edwin Vázquez-Rosa, Luxene Belfleur, Tanya L Díaz, Bismark Madera-Soto, Irving E Vega, José M Rivera","doi":"10.1021/acsabm.5c00201","DOIUrl":"10.1021/acsabm.5c00201","url":null,"abstract":"<p><p>Supramolecular hacky sacks (SHS) are a distinct class of self-assembled colloidal particles derived from guanosine (G) derivatives, engineered to support a wide range of cellular and therapeutic functions. In this study, we examine how variations in G-derivative composition influence SHS cellular uptake, intracellular trafficking, and functional efficacy. Confocal microscopy and flow cytometry reveal that uptake is highly dependent on particle composition, indicating selective engagement with specific cellular mechanisms. We show that SHS particles are biocompatible carriers capable of delivering both small molecules and genetic material: they successfully encapsulate and release doxorubicin with enhanced cytotoxic effects, and enable plasmid transfection with sustained expression of fluorescent proteins. These findings position SHS particles as a highly adaptable and effective supramolecular platform for drug and gene delivery. Their intrinsic biodegradability, ease of preparation, and tunable bioactivity highlight their strong potential for advancing biomedical applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"5625-5633"},"PeriodicalIF":4.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cody S Madsen, Ashley V Makela, Chima V Maduka, Emily M Greeson, Anthony Tundo, Evran Ural, Satyajit Hari Kulkarni, Ahmed A Zarea, Matti Kiupel, Maryam Sayadi, Christopher H Contag
{"title":"Engineered Endosymbionts that Modulate Primary Macrophage Function and Attenuate Tumor Growth by Shifting the Tumor Microenvironment.","authors":"Cody S Madsen, Ashley V Makela, Chima V Maduka, Emily M Greeson, Anthony Tundo, Evran Ural, Satyajit Hari Kulkarni, Ahmed A Zarea, Matti Kiupel, Maryam Sayadi, Christopher H Contag","doi":"10.1021/acsabm.5c00590","DOIUrl":"10.1021/acsabm.5c00590","url":null,"abstract":"<p><p>Modulating gene expression in macrophages can be used to improve tissue regeneration and redirect tumor microenvironments (TMEs) toward positive therapeutic outcomes. We have developed <i>Bacillus subtilis</i> as an engineered endosymbiont (EES) capable of residing inside the eukaryotic host cell cytoplasm and controlling the fate of macrophages. Secretion of mammalian transcription factors (TFs) from <i>B. subtilis</i> that expresses listeriolysin O (LLO; allowing the EES to escape destruction by the macrophage) modulated expression of surface markers, cytokines, and chemokines, indicating functional changes in a macrophage/monocyte cell line. The engineered <i>B. subtilis</i> LLO TF strains were evaluated in murine bone marrow-derived macrophages (BMDMs) by flow cytometry, chemokine/cytokine profiling, metabolic assays, and RNA-Seq delivery of TFs by the EES shifted BMDM gene expression, production of cytokine and chemokines, and metabolic patterns, indicating that the TF strains could guide primary macrophage function. Thereafter, the ability of the TF strains to alter the TME was characterized in vivo in an orthotopic murine model of triple-negative breast cancer to assess therapeutic effects. The TF strains altered the TME by shifting immune cell composition and attenuating tumor growth. Additionally, multiple doses of the TF strains were well-tolerated by the mice. The use of <i>B. subtilis</i> LLO TF strains as EES showed promise as a unique cancer immunotherapy by directing the immune function intracellularly. The uses of EES could be expanded to modulate other mammalian cells over a range of biomedical applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"5938-5958"},"PeriodicalIF":4.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
María E Pérez, Javier E Durantini, María E Milanesio, Edgardo N Durantini
{"title":"BODIPY-Loaded ZIF-8 Nanomaterials for Enhanced Photodynamic Inactivation of <i>Staphylococcus aureus</i>.","authors":"María E Pérez, Javier E Durantini, María E Milanesio, Edgardo N Durantini","doi":"10.1021/acsabm.5c00787","DOIUrl":"10.1021/acsabm.5c00787","url":null,"abstract":"<p><p>The rise of antibiotic-resistant pathogens has heightened the demand for innovative treatments, promoting advanced photodynamic materials for targeted microbial inactivation. Here, we report the synthesis of a series of photosensitizer nanomaterials consisting of BODIPY (BDP) dyes confined within ZIF-8, prepared via a straightforward one-pot nanoprecipitation method. The morphology of these materials was analyzed by SEM and TEM, and spectroscopic characterization confirmed the successful incorporation of BDP dyes within the porous ZIF-8 framework. Encapsulation significantly improved the ability of BDPs to generate reactive oxygen species (ROS) in aqueous media, with the brominated derivative, Br<sub>2</sub>BDP@ZIF-8, exhibiting particularly high production of singlet molecular and superoxide anion radicals. The photodynamic activity of Br<sub>2</sub>BDP@ZIF-8 was further demonstrated by its efficient degradation of tryptophan through a type II photoprocess. In addition, encapsulating BDPs within the ZIF-8 framework significantly enhanced their photostability compared with the free dyes. Antimicrobial assays revealed the strong potential of these nanomaterials for photoinactivation of <i>Staphylococcus aureus</i>. Under green light irradiation, Br<sub>2</sub>BDP@ZIF-8 achieved a 99.999% reduction in the bacterial population in liquid suspensions after exposure to a light fluence of 5 J/cm<sup>2</sup>. Fluorescence images of <i>S. aureus</i> showed the characteristic green fluorescence of BODIPY, indicating an effective interaction with BDP@ZIF-8. Furthermore, effective eradication of <i>S. aureus</i> contamination (>97%) was found on surfaces irradiated with only 0.9 J/cm<sup>2</sup>. These findings highlight the potential of BDP-loaded ZIF-8 nanomaterials as robust and efficient photosensitizing agents for bacterial elimination, offering promising applications in the photokilling of bacterial cells and surface decontamination.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"6316-6325"},"PeriodicalIF":4.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245185","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":"Multicolor Microscopic <i>In Vivo</i> Imaging of the Formation and Disappearance of Lipid Droplets Using BODIPY-Based Red and Deep-Red Fluorescent Probes.","authors":"Mayuko Shimanuki, Risa Uda, Shuichi Shiozaki, Toshitada Yoshihara","doi":"10.1021/acsabm.5c00698","DOIUrl":"10.1021/acsabm.5c00698","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. As the number and size of lipid droplets (LDs) generally increase in hepatocytes during the early stages of NAFLD, visualization of LDs in living samples is of great importance for properly diagnosing and treating NAFLD. Here, red and deep-red fluorescent probes (BPMP-2Thia and BPMP-4Thia) based on boron-dipyrromethene (4,4-difluoro-4-bora-3a,4a-diaza-<i>s</i>-indacene, BODIPY) are developed for the visualization of LDs in the liver of normal and NAFLD model mice as well as cultured cells. BPMP-2Thia and BPMP-4Thia exhibit bright emission in low-polarity solvents, which simulate the microenvironment of LDs, and they exhibit high selectivity for LDs, costaining capability, good biocompatibility, and high photostability in living cells and mice. Multicolor confocal microscopy combined with intravenous administration of an LD-specific probe, vascular endothelial marker, and nucleus-specific probe in mice enables the quantitative visualization of LD growth, including visualization of the disordered sinusoidal network and flattened hepatocyte nuclei. Furthermore, this simultaneous imaging method allows evaluation of the reduction in the number and size of LDs in the hepatic tissues of fatty liver model mice upon shifting from a high-fat to normal diet.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"6193-6202"},"PeriodicalIF":4.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281652","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}
Ihtisham Ahmad Butt, Peinan Yin, Naihan Chen, Wei Zhang
{"title":"α-Fe Nanoparticles and Multiwalled Carbon Nanotubes Composite with Improved Photothermal Conversion Efficiency for Tumor Therapy.","authors":"Ihtisham Ahmad Butt, Peinan Yin, Naihan Chen, Wei Zhang","doi":"10.1021/acsabm.5c00772","DOIUrl":"10.1021/acsabm.5c00772","url":null,"abstract":"<p><p>The efficiency of photothermal therapy based on conventional Fe<sub>3</sub>O<sub>4</sub> nanoparticles (NPs) is limited due to their low absorption in the near-infrared (NIR) region. To surmount this obstacle, α-Fe nanoparticles/multiwalled carbon nanotubes (MWCNTs) composite is synthesized by incipient wetness impregnation (IWI). Due to improved extinction and heat generation mechanism (plasmons/electrons thermalization) of metallic Fe NPs with in nanocomposite structure, the photothermal conversion efficiency of Fe/MWCNTs composite is 87.98% (content: 60 μg/mL, 808 nm at power density of 1 W/cm<sup>2</sup>), which is highest among the previously reported Fe<sub>3</sub>O<sub>4</sub> and other carbon-based nanostructures. The HaCaT cell viability after 72 h of coculturing is more than 91%, indicating the good biocompatibility of nanocomposite. The viability of B16-F10 melanoma cells is only 9.78% (808 nm laser irradiation for 15 min at 0.33 W/cm<sup>2</sup>), demonstrating the potential for hands-on applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"6291-6304"},"PeriodicalIF":4.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281653","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":"Exploring Lipid Droplets for Enhancing Cytoskeletal Stability and Repair Capacity via Carbonized Polymer Dot-Assisted Fluorescence Imaging.","authors":"Zitong Yu, Shuping Xu","doi":"10.1021/acsabm.5c00834","DOIUrl":"10.1021/acsabm.5c00834","url":null,"abstract":"<p><p>Lipid droplets (LDs), as dynamic organelles, are regarded as core carriers of energy storage and participate in cell signaling and metabolic process regulation. The interaction between LDs and cytoskeletons may profoundly affect cell growth and pathological processes; however, direct evidence is absent. Our study employed an LD-targeted carbonized polymer dot (CPD) that exhibits high photostability and superior imaging capabilities with confocal fluorescence imaging to visually observe the behaviors of LDs in reinforcing cytoskeletons and assisting cytoskeletal repair. Results demonstrate that LDs could enhance the stability of the cytoskeletons, helping cells resist damage from external factors. Once they were damaged, the LDs could quickly increase in content to facilitate cytoskeletal repair. These findings reveal the important role of LDs as \"regulatory hubs\" and offer fresh perspectives on the mechanism behind LD-cytoskeleton interactions.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"6360-6367"},"PeriodicalIF":4.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309234","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}
Shanmugavel Chinnathambi, Mahima Kumar, Basudeb Dutta, Karthikeyan Subramani, Saravanan Kandasamy, Sebastian Kmiecik, Thangavel Vaijayanthi, Ganesh N Pandian
{"title":"Structural Impact of Anthracene-Appended Mn-MOF on Human Serum Albumin and Its Cellular Implications.","authors":"Shanmugavel Chinnathambi, Mahima Kumar, Basudeb Dutta, Karthikeyan Subramani, Saravanan Kandasamy, Sebastian Kmiecik, Thangavel Vaijayanthi, Ganesh N Pandian","doi":"10.1021/acsabm.5c00887","DOIUrl":"10.1021/acsabm.5c00887","url":null,"abstract":"<p><p>Metal-organic frameworks (MOFs) are gaining attention as multifunctional nanomaterials for biomedical applications due to their porosity, tunable structure, and potential for molecular-level imaging. In this study, we synthesized green-emitting, water-dispersible manganese-based MOF (Mn-MOF) nanoparticles for live-cell imaging and investigated their interactions with human serum albumin (HSA). Spectroscopic analyses revealed high-affinity binding, with fluorescence quenching constants in the range of 10<sup>13</sup>. A red shift in emission and circular dichroism data confirmed that HSA retained its native conformation, underscoring the structural compatibility of Mn-MOFs. Biocompatibility was assessed using HeLa, A549, and chondrocyte cell lines. Cytotoxicity assays showed high cell viability at moderate concentrations and early time points. Nanoparticle size (∼18 nm by DLS; <10 nm by TEM) likely facilitated cellular uptake while minimizing toxicity. Confocal microscopy and flow cytometry revealed efficient internalization via multiple endocytic pathways, with perinuclear localization and no significant morphological changes. However, higher concentrations decreased cell adhesion and viability, indicating a dose-dependent toxicity threshold. These results demonstrate that Mn-MOF nanoparticles maintain protein integrity and exhibit low cytotoxicity, supporting their potential as safe, effective platforms for live-cell imaging and targeted delivery in nanomedicine.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"6397-6414"},"PeriodicalIF":4.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332036","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}