Shanlei Zhou, Yu Zhang, Eudald Casals, Muling Zeng, Manuel Morales-Ruiz, Qingshi Liu, Bo Zhang, Gregori Casals
{"title":"Mesoporous Silica-Encapsulated Cerium Oxide Nanozymes and Quercetin for Synergistic ROS-Modulated Downregulation of Inflammatory Cytokines.","authors":"Shanlei Zhou, Yu Zhang, Eudald Casals, Muling Zeng, Manuel Morales-Ruiz, Qingshi Liu, Bo Zhang, Gregori Casals","doi":"10.2147/IJN.S525411","DOIUrl":"10.2147/IJN.S525411","url":null,"abstract":"<p><strong>Introduction: </strong>Combining natural antioxidants with nanozymes represents a promising strategy to enhance therapeutic outcomes in oxidative stress-related diseases. This study integrates quercetin (Que), a plant-derived flavonoid with strong antioxidant activity, and cerium oxide nanozymes (CeO<sub>2</sub>NZs) into mesoporous silica (mSiO<sub>2</sub>) to enhance therapeutic efficacy and overcome the poor solubility and bioavailability of natural antioxidants.</p><p><strong>Methods: </strong>Large-pore mSiO₂ (11 nm) were synthesized via a sol-gel method to encapsulate cerium oxide nanozymes (CeO₂NZs). Que was loaded using solvent impregnation to obtain (CeO₂/Que)@mSiO₂ nanocomposites. Structural and chemical characterization was performed, and biological evaluations were conducted in A549 cells.</p><p><strong>Results: </strong>The incorporation of a large mesopore mSiO₂ (11 nm) significantly enhanced Que loading capacity and its sustained release in cell culture media. The (CeO₂/Que)@mSiO₂ nanocomposite demonstrated excellent biocompatibility, effective ROS scavenging, and significant downregulation of inflammatory cytokines (IL-1β, IL-6, TNF-α) compared to free Que.</p><p><strong>Conclusion: </strong>The (CeO₂/Que)@mSiO₂ nanoplatform offers synergistic antioxidant and anti-inflammatory effects, supporting its potential for treating oxidative stress-related inflammatory conditions.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"8191-8207"},"PeriodicalIF":6.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nermin Eissa, Jana K Alwattar, Petrilla Jayaprakash, Dana Chkier, Aala Osama Ahmed, Anum Ahmed, Rameen Rizwan, Sulthan Mujeeb, Mohamad Rahal, Bassem Sadek
{"title":"The Effects of Novel Thymoquinone-Loaded Nanovesicles as a Promising Avenue to Modulate Autism Associated Dysregulation by Restoring Oxidative Stress in Autism in Mice.","authors":"Nermin Eissa, Jana K Alwattar, Petrilla Jayaprakash, Dana Chkier, Aala Osama Ahmed, Anum Ahmed, Rameen Rizwan, Sulthan Mujeeb, Mohamad Rahal, Bassem Sadek","doi":"10.2147/IJN.S509158","DOIUrl":"10.2147/IJN.S509158","url":null,"abstract":"<p><strong>Introduction: </strong>Representing a prominent public health challenge with a surge in cases and no currently available treatment, autism spectrum disorder (ASD) remains a puzzle to researchers. Although the exact pathogenesis of this heterogeneous disorder is yet to be established, it has been reported that neural oxidative stress and neuroinflammation are eminently implicated. With numerous research establishing thymoquinone (TQ) as a potent antioxidant, this study assessed its effectiveness in the context of cognitive and social impairments and neural oxidative stress in the idiopathic autistic model in BTBR mice. Moreover, a novel TQ-loaded nanovesicle drug delivery system was optimized and utilized to enhance the bioavailability of TQ in the central nervous system.</p><p><strong>Methods: </strong>Through a battery of standard behavioral tests, primary parameters such as social behavior, locomotor activity, and anxiety levels were assessed following systemic administration with TQ (10mg/kg, i.p). Biochemical analysis of neural oxidative stress markers in the cerebellum and hippocampus tissue samples obtained from the different treatment groups was also performed.</p><p><strong>Results: </strong>The results indicated significant enhancements in sociability and social novelty preference of assessed BTBR mice treated with TQ-loaded nanovesicles (both p<0.01) as well as free TQ (p<0.05 and p<0.01, respectively). Moreover, BTBR mice treated with TQ-loaded nanovesicles also displayed restored levels of anxiety (p<0.05) and modulated hyperactivity parameters (p<0.05). In addition, and following biochemical assessments, our observations revealed marked alleviation of neural oxidative stress in BTBR mice treated with TQ-loaded nanovesicles, with restored levels of antioxidant proteins, reduced glutathione (p<0.01), and catalase (p<0.01), and diminished levels of the oxidative stress byproduct, malondialdehyde (p<0.01).</p><p><strong>Discussion: </strong>These preclinical observations unraveled compelling findings that reinforced TQ's antioxidant capacity, shedding new light on its potential as an effective therapeutic option for ASD. Thus, and with further experimentation, this study holds the potential to transition into a clinical study.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"8041-8061"},"PeriodicalIF":6.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Forgotten Innate Immune Cells: Unraveling Their Prospective Interactions with Nanomaterials.","authors":"África González-Fernández, Immacolata Maietta","doi":"10.2147/IJN.S517249","DOIUrl":"10.2147/IJN.S517249","url":null,"abstract":"<p><p>Nanomaterials, particularly nanoparticles, are revolutionizing various fields, including medicine, due to their distinctive physicochemical properties. Their large surface area, charge and high particle number per unit mass enable enhanced interactions with biological systems, particularly with the immune system. The interaction between nanomaterials and immune cells can influence immune responses in several ways, including modulating cell activation through interactions with pattern recognition receptors (PRRs), internalization, degradation, or accumulation in phagocytic cells, as well as altering the immune microenvironment through the release of granular contents, cytokines, and chemokines. Although many studies have focused primarily on phagocytic (macrophages, dendritic cells, and neutrophils) and Natural killer (NK) cells, less attention has been given to other innate immune cells such as eosinophils, basophils, and mast cells. This review aims to highlight the role of these \"forgotten\" innate immune cells, providing insights into their function, available cell lines, applicable techniques to understand interactions with nanomaterials, and relevant in vitro and in vivo models.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"8173-8189"},"PeriodicalIF":6.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging Targeted Delivery Strategies of Nanosystems for Ischemic Stroke Treatment.","authors":"Jia-Xin Ren, Hong-Yin Ma, Wen-Jing Yin, Yi-Kai Li, Shuang-Yin Lei, Jia-Cheng Liu, Yi Yang, Zhen-Ni Guo","doi":"10.2147/IJN.S519328","DOIUrl":"10.2147/IJN.S519328","url":null,"abstract":"<p><p>Ischemic stroke is a leading cause of death and severe disability worldwide. Current treatments mainly focus on reperfusion and neuroprotection. However, due to limitations like a narrow treatment window, single therapeutic targets, and side effects, drug therapy effectiveness is often unsatisfactory. Additionally, the blood-brain barrier (BBB) and the pathophysiological changes following ischemia pose challenges in stroke treatment. Recent developments in nanomaterials have enabled the design of multifunctional drug delivery nanosystems to advance stroke therapeutic approaches. These novel treatments significantly overcome the shortcomings of current therapies and improve efficacy. This review comprehensively summarizes innovative strategies for drug delivery nanosystems, which include crossing the BBB to target the ischemic region and controllable release in a responsive manner. Smart nanosystems, due to the modification of specific ligands and/or cell membranes, can cross the BBB to target the ischemic region for precise treatment, achieving controlled release and specific accumulation of drugs through intelligent molecular switching. Combining different strategies to build drug delivery nanosystems allows for positioning and targeted accumulation of drugs in the ischemic region, thereby extending the therapeutic time window and synergistically improving the neuroprotective effects. Such combinations provide a powerful strategy for developing novel ischemic stroke treatments and establishing targeting delivery nanosystems. Furthermore, the review summarizes the challenges encountered by multifunctional drug delivery nanosystems including clinical translation, drug loading capacity, and safety concerns, and potential solutions.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"8143-8171"},"PeriodicalIF":6.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanoparticles Loaded with Pralidoxime Wrapped in Tumor Cell Membranes: A New Strategy to Counteract the Central Nervous System Effects of Organophosphate Poisoning.","authors":"Huaizhi Jiang, Yanli Liu, Chu Wang, Yunyang Song, Fanghui Wu, Yifeng Yin, Zhanjun Yang","doi":"10.2147/IJN.S516233","DOIUrl":"10.2147/IJN.S516233","url":null,"abstract":"<p><strong>Purpose: </strong>In this study, cell membrane-coated nanoparticles (CMCNPs) were loaded with the organophosphorus antidote Pralidoxime Chloride (PAM) to improve the ability of the drug to penetrate the blood‒brain barrier (BBB) and evade immune clearance, providing a novel drug delivery strategy for the treatment of central organophosphorus poisoning.</p><p><strong>Methods: </strong>1) The cell membranes of mouse melanoma cells (B16F10), breast cancer cells (4T1), glioblastoma cells (GL261), and monocytic macrophage leukemia cells (RAW264.7) were extracted, and their purities were verified. The cell membranes were combined with PAM in mesoporous silica (SiO<sub>2</sub>) spheres by ultrasonic fusion to prepare the CMCNPs. 2) The immune evasion ability of CMCNPs was evaluated by laser confocal microscopy and flow cytometry after coculture with macrophages. 3) HPLC was used to screen the best CMCNPs through an in vitro BBB model. 4) After the CMCNPs were injected into malathion-poisoned mice, the phosphate chloride concentration in the peripheral blood and brain homogenates was tested, and the rate of acetylcholinesterase (AChE) reactivation was determined.</p><p><strong>Results: </strong>All four types of CMCNPs were spherical particles with diameters of approximately 100 nm. Compared with unwrapped nanoparticles, CMCNPs exhibited a stronger immune evasion ability and enhanced BBB penetration ability in an in vitro BBB model. They also significantly prolonged the in vivo circulation time of PAM, increased its delivery dose to the central nervous system, and markedly increased cholinesterase activity in brain tissues. Furthermore, in an organophosphorus-poisoned mouse model, CMCNPs significantly improved the survival rate of intoxicated mice.</p><p><strong>Conclusion: </strong>In this study, CMCNPs with a significant BBB penetration ability and immune evasion ability were successfully prepared and improved the therapeutic effect of PAM on central organophosphate poisoning.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"8101-8118"},"PeriodicalIF":6.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intranasal and Pulmonary Lipid Nanoparticles for Gene Delivery: Turning Challenges into Opportunities.","authors":"Yaman Tayyar, Adi Idris, Hadi Yassine","doi":"10.2147/IJN.S517385","DOIUrl":"10.2147/IJN.S517385","url":null,"abstract":"<p><p>Delivery of nano-therapeutics through the nasal route offers a promising approach for several applications, including intranasal conditions, pulmonary delivery, brain targeting, and vaccination. Despite its potential, this method faces significant challenges, including overcoming the mucosal barrier, ensuring consistent absorption, controlling the deposition area, and managing immunogenic responses. This review provides a comprehensive overview of the current state of nasally delivered lipid nanoparticles (LNPs) for gene medicine, focusing on the specific barriers encountered in this delivery route and strategies to overcome them. We examine how formulation composition affects stability during aerosolization, analyze the impact of particle characteristics on mucociliary clearance, and evaluate interactions with the lung surfactant layer. The review also compares delivery devices including metered-dose inhalers, dry powder inhalers, and nebulizers, highlighting how device selection influences LNP integrity and deposition patterns. Furthermore, we explore potential safety considerations with intranasal LNPs and propose approaches to mitigate adverse effects. By addressing these challenges with evidence-based strategies, this review aims to advance the development and clinical application of intranasal and pulmonary LNP delivery systems for gene-based therapeutics and vaccines.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"8085-8099"},"PeriodicalIF":6.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Wang, Yanxia Lin, Huijing Fan, Jianfeng Cui, Yuanxiang Wang, Zilan Wang
{"title":"ROS/pH Dual-Responsive Hydrogel Dressings Loaded with Amphiphilic Structured Nano Micelles for the Repair of Infected Wounds.","authors":"Jun Wang, Yanxia Lin, Huijing Fan, Jianfeng Cui, Yuanxiang Wang, Zilan Wang","doi":"10.2147/IJN.S522589","DOIUrl":"10.2147/IJN.S522589","url":null,"abstract":"<p><strong>Background: </strong>Bacterial infections in wounds have emerged as an increasingly significant healthcare concern. The toxins secreted by bacteria cause persistent inflammation and excessive oxidative stress, resulting in serious tissue damage and ultimately delay wound healing.</p><p><strong>Methods: </strong>Herein, a ROS/pH dual-responsive hydrogel dressing loaded with amphiphilic structured nano micelles was developed for efficiently promoting infected wound healing. First, chitosan-grafted α-lipoic acid (CSLA) and curcumin (Cur) formed stable amphiphilic nano micelles (CSLA@Cur) through ultrasonic self-assembly. Subsequently, CSLA@Cur was incorporated into a hydrogel formed from 4-carboxyphenylboronic acid-modified gelatin methacrylate (GelMA-CPBA) and oxidized chondroitin sulfate (OCS) via Schiff base formation, boronate ester bonding, and free radical polymerization to obtain GC/OCS-CL@Cur hydrogel dressing. The mechanical properties, antimicrobial, antioxidant, and ROS/pH responsiveness of GC/OCS-CL@Cur were evaluated. Cellular assays were performed to investigate the biocompatibility of GC/OCS-CL@Cur and its role in promoting angiogenesis, scavenging intracellular ROS and regulating macrophage polarization. A full-thickness skin defect rat model with bacterial infection was established to investigate the ability of GC/OCS-CL@Cur to enhance wound repair in vivo.</p><p><strong>Results: </strong>The unique cross-linked structure of GC/OCS-CL@Cur significantly improves the mechanical properties of hydrogels. Importantly, GC/OCS-CL@Cur exhibited sensitive ROS/pH dual responsiveness, which enabled the controlled release of CSLA@Cur and efficient delivery of Cur. Moreover, GC/OCS-CL@Cur possessed excellent antimicrobial activity and efficient ROS scavenging ability. In vitro cellular assays demonstrated that GC/OCS-CL@Cur could effectively scavenge intracellular ROS (up to 90% scavenging ratio), promote macrophage polarization to M2 phenotype, and enhance angiogenesis. In vivo experiments showed that GC/OCS-CL@Cur significantly regulated the expression level of inflammatory cytokines, and healed more than 95% of wounds in 14 days, showing excellent wound healing ability.</p><p><strong>Conclusion: </strong>These results demonstrate the successful development of a dual-responsive (ROS/pH) hydrogel dressing with integrated antibacterial, antioxidant, and anti-inflammatory properties, showcasing significant potential for treating infected wounds.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"8119-8142"},"PeriodicalIF":6.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Molenda, Tomasz Deptuch, Agata Sikorska, Patryk Lorenc, Maciej Jerzy Smialek, Anna Florczak-Substyk, Piotr Pawlak, Hanna Dams-Kozlowska
{"title":"Developing the Strategy to Use Silk Spheres for Efficient, Targeted Delivery of Oligonucleotide Therapeutics to Cancer Cells.","authors":"Sara Molenda, Tomasz Deptuch, Agata Sikorska, Patryk Lorenc, Maciej Jerzy Smialek, Anna Florczak-Substyk, Piotr Pawlak, Hanna Dams-Kozlowska","doi":"10.2147/IJN.S519906","DOIUrl":"10.2147/IJN.S519906","url":null,"abstract":"<p><strong>Introduction: </strong>Oligonucleotide-based drugs, such as siRNA, hold great promise for disease treatment, including cancer. However, their clinical application has challenges related to cell-specific delivery and susceptibility to degradation. The use of drug delivery systems (DDS) may address these problems. Nanoparticles of bioengineered spider silk demonstrate significant potential as DDS due to their biocompatibility and biodegradability. Another advantage of this material is the possibility of functionalization, which allows the control of its property. The main objective of this study was to develop a strategy for targeted delivery of oligonucleotide-based therapeutics into cancer cells using bioengineered silk technology.</p><p><strong>Materials and methods: </strong>Two spider silk spheres that bind oligonucleotides and target cancer cells that overexpress HER2 (HER2+) were constructed. One type of sphere was made of a newly designed silk, H2.1MS1KN, which contained two functional peptides: H2.1 for binding HER2 and KN for binding oligonucleotide. The second type of sphere was formed of a blend of two previously described proteins, H2.1MS1 and MS2KN; these proteins differed not only in the functional domain (H2.1 vs KN) but also in the sequence of silk (MS1 vs MS2). The ability of proteins to bind oligonucleotides was analyzed via gel electrophoresis. The biophysicochemical properties of particles were analyzed using an SEM, NanoSight, ZetaSizer, flow cytometry, and scanning confocal microscopy. The silk particle potential was analyzed using siRNA for silencing <i>STAT3</i> expression in the HER2+ breast cancer model.</p><p><strong>Results: </strong>Both H2.1MS1KN and H2.1MS1:MS2KN proteins efficiently bound nucleic acid. H2.1MS1:MS2KN formed smaller spheres than H2.1MS1KN. Although both H2.1MS1KN and blended H2.1MS1:MS2KN spheres were effectively loaded with oligonucleotides, only H2.1MS1:MS2KN spheres delivered siRNA to HER2+ cancer cells that successfully silenced <i>STAT3</i> expression.</p><p><strong>Conclusion: </strong>Not only the selection of functional peptides but also their quantity and type of silk is crucial when developing an effective silk-based DDS for delivering active siRNA.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"8023-8039"},"PeriodicalIF":6.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tumor Microenvironment-Responsive Nanoparticles: Promising Cancer PTT Carriers.","authors":"Heming Sun, Yuebo Li, Ming Xue, Dingqing Feng","doi":"10.2147/IJN.S526497","DOIUrl":"10.2147/IJN.S526497","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is often characterized by distinctive features such as hypoxia, low pH, the overexpression of extracellular matrix-degrading enzymes, and increased redox reactions. These attributes create a specialized internal environment that promotes tumor cell survival and proliferation, thereby facilitating tumor development, metastasis, and the emergence of drug resistance. These challenging aspects pose significant hurdles to the efficacy of traditional cancer therapies. However, they also offer unique opportunities for the development of responsive nanomedicines that specifically target the TME to improve treatment outcomes for cancer patients when combined with photothermal therapy (PTT). This review provides an overview of the predominant features of the TME and delves into recent advancements in the field of nanomedicine, with a special focus on TME-responsive nanomedicines. Each type of TME-responsive nanomedicine is reviewed for its potential value in drug delivery in combination with PTT and chemotherapy, which may enable effective multimodal antitumor therapy. Finally, the review discusses the challenges and opportunities associated with the use of TME-responsive nanomaterials in PTT, highlighting the potential for these innovative strategies to overcome current therapeutic limitations and improve patient outcomes.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"7987-8001"},"PeriodicalIF":6.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rosa I Ruvalcaba-Ontiveros, Hilda E Esparza-Ponce, Reyna Reyes-Martínez, Laura A Manjarrez-Nevárez, Valente Gómez-Benítez, Hilda A Piñon-Castillo
{"title":"Antibacterial Activity of CuO Nanoparticles, Ethanolic Extract of <i>Amphipterygium adstringens</i>, and Their Combination Against Multidrug-Resistant Bacteria.","authors":"Rosa I Ruvalcaba-Ontiveros, Hilda E Esparza-Ponce, Reyna Reyes-Martínez, Laura A Manjarrez-Nevárez, Valente Gómez-Benítez, Hilda A Piñon-Castillo","doi":"10.2147/IJN.S517465","DOIUrl":"10.2147/IJN.S517465","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigated the incorporation of <i>Amphipterygium adstringens</i> ethanolic extract into the synthesis of copper oxide nanoparticles (CuO+Aa) and evaluates their antibacterial activity against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB). To assess the impact of the extract, chemically synthesized CuO nanoparticles (CuO-NPs) and the extract alone were also tested. Both CuO-NPs and <i>A. adstringens</i> are known for their antimicrobial properties.</p><p><strong>Methods: </strong>CuO+Aa nanoparticles were synthesized using <i>A. adstringens</i> extract and characterized through Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Zeta Potential, Thermogravimetric Analysis (TGA), and X-ray Diffraction (XRD), and compared to CuO-NPs. The influence of the extract was analyzed using Inductively Coupled Plasma Mass Spectroscopy (ICP-MS), UV-Vis, FTIR, Raman, and Nuclear Magnetic Resonance Spectroscopy (NMR). Antibacterial effects were tested using the microdrop technique and biofilm inhibition. Bacterial structural changes were observed via Scanning Electron Microscopy (SEM), and cytotoxicity was measured through hemolysis assays.</p><p><strong>Results: </strong>CuO+Aa nanoparticles were smaller (3.46 nm) than CuO-NPs (5.32 nm). TGA indicated improved thermal degradation in CuO+Aa, suggesting incorporation of organic compounds. XRD revealed a shift from CuO to a mixed CuO-Cu<sub>2</sub>O phase (75.15%-24.84%) in CuO+Aa due to the functional groups present in the extract. Antibacterial assays showed that CuO+Aa inhibited MRSA and CRAB by 77% and 49%, respectively, using only 17.5 ppm of copper oxides-significantly lower than CuO-NPs, which required 150 ppm to achieve 96% and 78% inhibition. SEM revealed bacterial surface damage, including roughness, perforations, and cell wall collapse. All treatments showed low cytotoxicity (<2% hemolysis). Biofilm formation increased by 180% in MRSA and 131% in CRAB.</p><p><strong>Conclusion: </strong><i>A. adstringens</i> ethanolic extract enhances CuO nanoparticle synthesis, reducing size and maintaining strong antibacterial activity with low toxicity. CuO+Aa represents a promising candidate for future biomedical applications against resistant pathogens.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"8003-8022"},"PeriodicalIF":6.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}