Nanoparticle Platform Research Articles

Recent Development of Nanoparticle Platforms for Organophosphate Nerve Agent Detoxification.

Poisoning by organophosphate (OP) nerve agents remains a pressing global threat due to their extensive use in chemical warfare agents and pesticides, potentially causing high morbidity and mortality worldwide. This urgent need for effective countermeasures has driven considerable interest in innovative detoxification approaches. Among these, nanoparticle technology stands out for its multifunctional potential and wide-ranging applications. This review highlights recent advancements in nanoparticle platforms developed for OP detoxification, focusing on five main types: inorganic nanoparticles, lipid-based nanoparticles, polymer-based nanoparticles, metal-organic framework nanoparticles, and cellular nanoparticles. For each platform, we discuss representative examples that illustrate how structural and functional properties enhance their effectiveness as nanocarriers, nanocatalysts, or nanoscavengers, ultimately enabling safe and efficient OP detoxification. This review aims to stimulate further technological innovation in OP-detoxifying nanoparticles and encourage broader development of detoxification strategies.

Synergistic photothermal and chemo-therapeutic platform utilizing Cu2-xSe/PDA/AIPH nanoparticles for targeted tumor eradication.

In this study, we developed an innovative Cu2-xSe/PDA/AIPH nanoparticle platform that combines photothermal therapy and chemotherapy for effective tumor treatment. The Cu2-xSe nanoparticles, known for their strong near-infrared (NIR) absorption, were encapsulated within a polydopamine (PDA) and 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) matrix. Upon NIR irradiation, the platform triggers localized heating and subsequent thermal decomposition of AIPH, releasing ROS to induce significant oxidative damage in tumor cells. In vitro and in vivo experiments demonstrated that Cu2-xSe/PDA/AIPH nanoparticles exhibit excellent biocompatibility, effective photothermal conversion, and potent anticancer efficacy. This multifunctional nanosystem offers a promising approach for enhancing tumor therapy by combining PTT with ROS-mediated chemotherapy.

Organelle-Targeting Nanoparticles.

Organelles are specialized subunits within cells which carry out vital functions crucial to cellular survival and form a tightly regulated network. Dysfunctions in any of these organelles are linked to numerous diseases impacting virtually every organ system in the human body. Targeted delivery of therapeutics to specific organelles within the cell holds great promise for overcoming challenging diseases and improving treatment outcomes through the minimization of therapeutic dosage and off-target effects. Nanoparticles are versatile and effective tools for therapeutic delivery to specific organelles. Nanoparticles offer several advantageous characteristics, including a high surface area-to-volume ratio for efficient therapeutic loading and the ability to attach targeting moieties (tethers) that enhance delivery. The choice of nanoparticle shape, size, composition, surface properties, and targeting ligands depends on the desired target organelle and therapeutic effect. Various nanoparticle platforms have been explored for organelle targeting, such as liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles. In this review, current and emerging approaches to nanoparticle design are examined in the context of various diseases linked to organelle dysfunction. Specifically, advances in nanoparticle therapies targeting organelles such as the nucleus, mitochondria, lysosomes/endosomes, Golgi apparatus, and endoplasmic reticulum are comprehensively and critically discussed.

Polysialic acid-based nanoparticles for enhanced targeting and controlled dexamethasone release in pulmonary inflammation treatment.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions characterized by severe inflammation and respiratory failure. Despite the use of dexamethasone (Dex) in treatment, challenges such as poor solubility and systemic side effects persist, highlighting the need for novel therapeutic approaches. This study introduces an innovative nanoparticle delivery system based on chitosan (CS) and polysialic acid (PSA), engineered via electrostatic assembly, to improve the targeted delivery of Dex to inflamed lung tissues. To enhance drug encapsulation and stability, novel taurine-Vitamin E succinate amphiphilic molecules (TVES and TGVES) were synthesized. The unique ability of PSA to specifically target Siglec-1 receptors on M1 macrophages-key contributors to ALI/ARDS-related inflammation-positions this system as a promising strategy for targeted pulmonary therapies. In vitro targeting of M1 macrophages and in vivo reduction of inflammation demonstrate the potential to transform treatment by delivering therapeutic agents precisely to the site of need. This cutting-edge nanoparticle platform not only holds promise for improving ALI/ARDS outcomes but also paves the way for the application of functional additives like taurine in advanced medical therapies.

Oral delivery of MOMIPP lipid nanoparticles for methuosis-induced cancer chemotherapy.

Methuosis, a non-apoptotic pattern of cell death, triggers the accumulation of macropinosome-derived vacuoles in the cytoplasm. Through this novel mechanism, methuosis inducers possess great potential in fighting apoptosis-resistant cancer cells and offer a promising alternative for cancer treatment. However, the potent methuosis inducer, 3-(5-methoxy, 2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP), faces an intractable issue of insolubility in most solvents, hindering in vivo dosing and compromising the validation of its antitumor efficacy. Few strategies have been developed to effectively deliver MOMIPP and achieve robust in vivo tumor inhibition since its first report in 2012. Here, a MOMIPP self-emulsifying drug delivery system (MOMIPP-SEDDS) was developed to substantially improve its oral bioavailability and achieve a favorable antitumor effect in a mouse xenograft tumor model. Our findings demonstrated that the MOMIPP-SEDDS was internalized into Caco-2 cells via the lipid raft/caveolae pathway and exhibited enhanced absorption in both cell monolayers and everted gut sacs. Compared with MOMIPP suspensions, MOMIPP-SEDDS showed a 13.3-fold increase in peak concentration and increased relative bioavailability by 19.98 times. By inducing methuosis, MOMIPP-SEDDS successfully retarded tumor progression in a subcutaneous HeLa mouse tumor model. Additionally, transmission electron microscopy (TEM) images of the tumor sections evidenced the occurrence of methuosis in the MOMIPP-SEDDS treatment group. This MOMIPP-SEDDS emerges as a promising lipid nanoparticle platform and high translational medicine for the oral delivery of MOMIPP to exert methuosis-induced tumor suppression for cancer treatment.

Peptide-Functionalized Lipid Nanoparticles for Targeted Systemic mRNA Delivery to the Brain.

Systemic delivery of large nucleic acids, such as mRNA, to the brain remains challenging in part due to the blood-brain barrier (BBB) and the tendency of delivery vehicles to accumulate in the liver. Here, we design a peptide-functionalized lipid nanoparticle (LNP) platform for targeted mRNA delivery to the brain. We utilize click chemistry to functionalize LNPs with peptides that target receptors overexpressed on brain endothelial cells and neurons, namely the RVG29, T7, AP2, and mApoE peptides. We evaluate the effect of LNP targeting on brain endothelial and neuronal cell transfection in vitro, investigating factors such as serum protein adsorption, intracellular trafficking, endothelial transcytosis, and exosome secretion. Finally, we show that LNP peptide functionalization enhances mRNA transfection in the mouse brain and reduces hepatic delivery after systemic administration. Specifically, RVG29 LNPs improved neuronal transfection in vivo, establishing its potential as a nonviral platform for delivering mRNA to the brain.

Two-in-one nanoparticle platform induces a strong therapeutic effect of targeted therapies in P-selectin-expressing cancers.

Combined therapies in cancer treatment aim to enhance antitumor activity. However, delivering multiple small molecules imposes challenges, as different drugs have distinct pharmacokinetic profiles and tumor penetration abilities, affecting their therapeutic efficacy. To circumvent this, poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-based nanoparticles were developed as a platform for the codelivery of synergistic drug ratios, improving therapeutic efficacy by increasing the percentage of injected dose reaching the tumor. Nonetheless, extravasation-dependent tumor accumulation is susceptible to variations in tumor vasculature; therefore, PLGA-PEG was modified with sulfates to actively target P-selectin-expressing cancers. Here, we show the potential of our platform in unique three-dimensional (3D) in vitro and in vivo models. The P-selectin-targeted nanoparticles showed enhanced accumulation in 3D spheroids and tissues of P-selectin-expressing BRAF-mutated melanomas and BRCA-mutated breast cancers, resulting in superior in vivo efficacy and safety. This nanoplatform could advance the codelivery of a plethora of anticancer drug combinations to various P-selectin-expressing tumors.

From Frustration to Order: Role of Fluid-Fluid Interfaces in Precision Assembly of Nanoparticles.

Fluid-fluid interfaces are an attractive platform for self-assembling nanoparticles into low-dimensional materials. In this Perspective, we review recent developments in the use of interfaces to direct the assembly of spherical and anisotropic nanoparticles into diverse and sophisticated architectures. We illustrate how nanoparticle clusters, strings, networks, superlattices, chiral lattices, and quasicrystals can be self-assembled by harnessing the frustration between interfacial and interparticle forces. We highlight the role of polymeric ligands attached to the surface of nanoparticles in modulating assembly behavior by directly altering particle-fluid and particle-particle interactions or by deforming at interfaces and junctions between particles. We conclude by providing a roadmap of key questions and opportunities in this exciting field of interfacial assembly.

Challenges in AAV-Based Retinal Gene Therapies and the Role of Magnetic Nanoparticle Platforms.

Retinal diseases, leading to various visual impairments and blindness, are on the rise. However, the advancement of retinal gene therapies offers new hope for treatment of such diseases. Among different vector systems for conferring therapeutic genetic load to retinal cells, adeno-associated viruses (AAVs) have been most intensively explored and have already successfully gained multiple clinical approvals. AAV-based retinal gene therapies have shown great promise in treating retinal disorders, but usually rely on the heavily disruptive administration methods such as subretinal injection. This is because the clinically well-established, minimally invasive alternative of intravitreal injection (IVI) necessitates AAVs to traverse the retinal inner limiting membrane (ILM), which is hard to penetrate in higher eye models, like human or porcine eyes. Additionally, AAVs' natural transduction preference, known as tropism, is commonly not specific to cells of only one target retinal layer, which is another ongoing challenge in retinal gene therapy. This review examines strategies to overcome these obstacles with a focus on the potential of magnetic nanoparticles (MNPs) for improved retinal AAV delivery.

Impaired Biofilm Development on Graphene Oxide-Metal Nanoparticle Composites.

Biofilms are one of the main threats related to bacteria. Owing to their complex structure, in which bacteria are embedded in the extracellular matrix, they are extremely challenging to eradicate, especially since they can inhabit both biotic and abiotic surfaces. This study aimed to create an effective antibiofilm nanofilm based on graphene oxide-metal nanoparticles (GOM-NPs). To create nanofilms, physicochemical analysis was performed, including zeta potential (Zp) (and the nanocomposites stability in time) and size distribution measurements, scanning transmission electron microscopy (STEM), energy dispersive X-ray analysis (EDX), and atomic force microscopy (AFM) of the nanofilm surfaces. During biological analysis, reactive oxygen species (ROS) and antioxidant capacity were measured in planktonic cells treated with the nanocomposites. Thereafter, biofilm formation was checked via crystal violet staining, biofilm thickness was assessed by confocal microscopy using double fluorescent staining, and biofilm structure was analyzed by scanning electron microscopy. The results showed that two of the three nanocomposites were effective in reducing biofilm formation (GOAg and GOZnO), although the nanofilms were characterized by the roughest surface, indicating that high surface roughness is unfavorable for biofilm formation by the tested bacterial species (Staphylococcus aureus (ATCC 25923), Salmonella enterica (ATCC 13076), Pseudomonas aeruginosa (ATCC 27853)). The performed analysis indicated that graphene oxide may be a platform for metal nanoparticles that enhances their properties (eg colloidal stability, which is maintained over time). Nanocomposites based on graphene oxide with silver nanoparticles and other types of nanocomposites with zinc oxide were effective against biofilms, contributing to changes throughout the biofilm structure, causing a significant reduction in the thickness of the structure, and affecting cell distribution. A nanocomposite consisting of graphene oxide with copper nanoparticles inhibited the biofilm, but to a lesser extent.

PET/CT-guided and OPN-targeted melanin nanoparticle platform for early diagnosis and precision therapy of idiopathic pulmonary fibrosis (IPF)

PET/CT-guided and OPN-targeted melanin nanoparticle platform for early diagnosis and precision therapy of idiopathic pulmonary fibrosis (IPF)

A plug-and-play strategy for agrochemical delivery using a plant virus nanotechnology

Delivery of agrochemicals into soil presents a challenge, as the active ingredients are often hydrophobic and do not possess adequate soil mobility to reach their target pest. Previously, plant virus nanoparticles have been shown to penetrate soil and deliver agrochemicals for the treatment of plant parasitic nematodes. For example, tobacco mild green mosaic virus (TMGMV) can be functionalized with agrochemicals through bioconjugation, infusion at the coat protein interface, or encapsulation through thermal shapeshifting (rod-to-sphere). There continues to be a need to expand approaches for agrochemical display and delivery with a need for plug-and-play technology to be applicable for multiple nanoparticle platforms and agrochemicals. Toward this goal, we turned toward a bio-specific coupling strategy making use of the biotin-(strept)avidin system. Herein, we conjugated TMGMV with either avidin or biotin using azide-alkyne cycloaddition. The avidin/biotin-functionalized TMGMV nanoparticles were then characterized by gel electrophoresis and electron microscopy to confirm cargo loading and the nanoparticle’s structural integrity. Soil column assays confirmed that soil mobility was maintained upon chemical modification. Ivermectin modified with biotin or streptavidin linkers was then introduced to the TMGMV-avidin/biotin nanoparticles and binding propensity and loading were validated by QCM-D and a competitive ELISA. Finally, the ivermectin-loaded TMGMV nanoparticles were used to treat C. elegans in a gel burrowing assay, demonstrating that either pesticide loading strategy resulted in active TMGMV nanoparticle formulation that significantly reduced the mobility of nematodes, even after passing through soil. In stark contrast, free ivermectin only exhibited efficacy when applied directly to nematodes; the free pesticide was lost in the soil column—highlighting the need for a delivery system. The presented approach provides a facile plug-and-play approach for pesticide loading onto TMGMV nanoparticles. In particular, biotinylated TMGMV with streptavidin-conjugated ivermectin served as the most effective formulation. Importantly this method does not require heat, which contrasts our previous method of thermal reshaping that requires sample and pesticide exposure to temperatures > 96 °C. We envision the bio-specific loading strategy could be extended to other protein or inorganic nanoparticles to advance soil treatment strategies.

Preparation and characterizations of chitosan–octanoate nanoparticles for efficient delivery of curcumin into prostate cancer cells

The goal of the research was to develop a hydrophobic octanoate salt of chitosan (CS–OA) and use the salt as a nanoparticle platform for the delivery of curcumin (CUR) into prostate cancer cells. The nanoprecipitation technique was used to prepare the nanoparticles, which were measured for particle size and encapsulation efficacy relative to CUR–CS nanoparticles. The cytotoxicity of CUR–OA–CS nanoparticles was evaluated in prostate cancerous cells (PC3 and DU145) in comparison with the corresponding blank nanoparticles and hydroalcoholic CUR solution. PXRD, SEM, and TEM were also used to examine the CUR–CS–OA nanoparticles. The average diameters of the CUR–CS–OA and CUR–CS nanoparticles were 268.90 ± 3.77 nm and 221.90 ± 2.79 nm, respectively, with encapsulation efficiencies of 61.37 ± 1.70% and 60.20 ± 3.17%. PXRD and SEM suggested CUR amorphization in the CS–OA nanoparticles. The void nanoparticles exhibited concentration-dependent antiproliferative action, which was attributed to the cellular uptake of CS. CUR loading into these nanoparticles increased their cytotoxicity even more. The potential of CS–OA nanoparticles as a special delivery system for additional cytotoxic drugs into different malignant cells can be further explored.

Nanoparticle-Assisted Cancer Imaging and Targeted Drug Delivery for Early-Stage Tumor Detection and Combined Diagnosis-Therapy Systems for Improved Cancer Management

Nanoparticle-assisted imaging and targeted drug delivery represent a transformative approach in cancer diagnostics and therapeutics, particularly for early-stage tumor detection and integrated diagnosis- therapy systems. This review explores recent advancements in nanoparticle technology for magnetic resonance imaging (MRI), computed tomography (CT), optical imaging, and ultrasound, emphasizing the efficacy of nanoparticles such as superparamagnetic iron oxide nanoparticles (SPIONs), gold and bismuth nanoparticles, and quantum dots as contrast agents. Nanoparticles offer unique advantages, including enhanced permeability and retention (EPR) effects, ligand-receptor targeting, and microenvironment-responsive drug release, which improve localization and accumulation in tumor tissues. Additionally, dual-function theranostic systems utilizing nanoparticles enable simultaneous diagnostic imaging and therapy, allowing real-time monitoring of therapeutic efficacy and minimizing off-target effects. The integration of nanoparticles for both diagnostic and therapeutic purposes holds significant promise for precision oncology, providing a more personalized, minimally invasive, and effective cancer management strategy. This review also discusses current limitations, including issues of biocompatibility, toxicity, and regulatory challenges, while proposing future directions to overcome these barriers. By presenting a comprehensive analysis of nanoparticle platforms in oncology, this paper aims to underscore their potential in revolutionizing cancer diagnosis and therapy, ultimately contributing to improved patient outcomes and advancing the field of nanomedicine.

Nucleus-targeted Silencer nanoplatform regulating ZEB1-AS1 in head and neck squamous cell carcinoma therapy

Long noncoding RNAs have emerged as key players in the progression of head and neck squamous cell carcinoma (HNSC). Among them, ZEB1-AS1 was identified as an upregulated candidate in HNSC through comprehensive analysis of RNA-sequencing datasets. Here, elevated ZEB1-AS1 expression was correlated with poor prognosis in HNSC patients. Further investigations demonstrated that downregulation of ZEB1-AS1 induced epithelial-mesenchymal transition and increased sensitivity to cisplatin in Cal27 cells, while its upregulation reversed these effects, underscoring its pivotal role in tumor metastasis and cisplatin resistance in Cal27 cells. Mechanistically, ZEB1-AS1, located in cytoplasm and nucleus, directly regulated the expression of ZEB1, thereby influencing the expression of μ opioid receptor (MOR) and implicating in cancer progression. To advance clinical translation, we employed a nucleus-targeting nanoparticle platform for efficient delivery of a mixture of antisense oligonucleotides and siRNA (Silencer), effectively manipulating ZEB1-AS1 expression in vitro and in vivo. Besides, a predictive model for HNSC patients was developed by analyzing the expression levels of ZEB1-AS1, ZEB1, and MOR in the HNSC datasets. Our study underscored the critical role of ZEB1-AS1 in HNSC and its potential as a therapeutic target. By elucidating its functional mechanisms and utilizing a nucleus-targeting nanoparticle platform for efficient delivery, we proved the potential of ZEB1-AS1-targeted therapies in HNSC.

Conjugation of Antibodies and siRNA Duplexes to Polymer Nanoparticles via Maleimide-Thiol Chemistry.

Polymeric nanoparticles (NPs) have shown great promise as highly modifiable platforms that can be applied across many different disease states. They are advantageous because they can encapsulate a range of hydrophobic and hydrophilic cargoes while having customizable surface properties. Depending on the desired biointerfacing capabilities, the surface of polymeric NPs can be modified with moieties, such as antibodies, peptides, nucleic acids, and more. The work presented here is intended to provide mechanistic insight into how different parameters influence the loading of antibodies, small interfering ribonucleic acids (siRNAs), or both on the surface of poly(lactic-co-glycolic acid) (PLGA) NPs via maleimide-thiol chemistry. Some of the conjugation parameters investigated include the buffer concentration, maleimide to protein ratio, and the addition of an excipient such as Tween-20. Through variation in the concentration of FZD7 antibodies added to the reaction mixture, we established tunable conjugation and found the upper limit of their loading density under the conditions tested. We also confirmed antibody conjugation through two different mechanisms: via a thiol-modified antibody or a thiol-modified poly(ethylene glycol) (PEG) linker. Conjugation of thiolated siRNA duplexes targeting β-catenin was also investigated through variations in both Tween-20 concentration and CaCl2 buffer concentration. Finally, the coconjugation of both antibodies and siRNA duplexes was explored. Overall, this work outlines a basis for tunable biomolecule loading on polymer NPs using maleimide-thiol chemistry and reveals the incredible versatility of polymer NP platforms.

Nanoparticles Codelivering mRNA and SiRNA for Simultaneous Restoration and Silencing of Gene/Protein Expression In Vitro and In Vivo.

RNA-based agents (siRNA, miRNA, and mRNA) can selectively manipulate gene expression/proteins and are set to revolutionize a variety of disease treatments. Nanoparticle (NP) platforms have been developed to deliver functional mRNA or siRNA inside cells to overcome their inherent limitations. Recent studies have focused on siRNA to knock down proteins causing drug resistance or mRNA technology to introduce tumor suppressors. However, cancer needs multitargeted approaches to selectively manipulate multiple gene expressions/proteins. In this proof-of-concept study, we developed NPs containing Luc-mRNA and siRNA-GFP as model agents ((M+S)-NPs) and showed that NPs can simultaneously deliver functional mRNA and siRNA and impact the expression of two genes/proteins in vitro. Additionally, after in vivo administration, (M+S)-NPs successfully knocked down GFP while introducing luciferase into a TNBC mouse model, indicating that our NPs have the potential to develop RNA-based anticancer therapeutics. These studies pave the way to develop RNA-based, multitargeted approaches for complex diseases like cancer.

Combination application of Pickering emulsion and BLS protein nanoparticles enhances vaccine efficacy

The deficiency of recombinant protein immune response could be compensated for by using nanoparticle platforms or adding immune enhancers, however existing vaccines or adjuvants struggle to elicit durable cellular immune responses. In this work, a protein nanoscaffold, lumazine synthase isolated from Brucella (BLS) was optimally designed that could facilitate cellular uptake of displayed antigens and the maturation of bone marrow-derived dendritic cells (BMDCs), and enhancing humoral immune responses. To enhance cellular immune response, chitosan hydrochloride-stabilized Pickering emulsion (CHSPE) was evaluated as an adjuvant for the BLS nanoscaffold-based vaccine. CHSPE could enhance the recruitment and activation of DCs at the injection site and the uptake of antigen and activation of DCs in the draining lymph nodes (dLNs), compared with commercial adjuvant ISA 206. In addition, CHSPE induced antigen-specific antibody levels comparable to those of ISA 206 and increased the ratio of central memory T cells (TCM) and effector memory T cells (TEM), and promoted the secretion of Th1-type cytokines. Moreover, CHSPE-formulated vaccine provided a similar level of protection to the live attenuated vaccine and was superior to that of ISA 206. Taken together, the combination of the BLS nanoscaffold and CHSPE provides a feasible strategy for recombinant protein subunit vaccine development.

MRNA delivery enabled by metal–organic nanoparticles

mRNA therapeutics are set to revolutionize disease prevention and treatment, inspiring the development of platforms for safe and effective mRNA delivery. However, current mRNA delivery platforms face some challenges, including limited organ tropism for nonvaccine applications and inflammation induced by cationic nanoparticle components. Herein, we address these challenges through a versatile, noncationic nanoparticle platform whereby mRNA is assembled into a poly(ethylene glycol)-polyphenol network stabilized by metal ions. Screening a range of components and relative compositional ratios affords a library of stable, noncationic, and highly biocompatible metal–organic nanoparticles with robust mRNA transfection in vitro and in mice. Intravenous administration of the lead mRNA-containing metal–organic nanoparticles enables predominant protein expression and gene editing in the brain, liver, and kidney, while organ tropism is tuned by varying nanoparticle composition. This study opens an avenue for realizing metal–organic nanoparticle-enabled mRNA delivery, offering a modular approach to assembling mRNA therapeutics for health applications.

Nanoparticle-Based Nitric Oxide Donors: Exploring Their Antimicrobial and Anti-Biofilm Capabilities.

Background: Nitric oxide (NO) is an antimicrobial and anti-biofilm agent with significant potential for combating biofilm-associated infections and antibiotic resistance. However, owing to its high reactivity due to the possession of a free radical and short half-life (1-5 s), the practical application of NO in clinical settings is challenging. Objectives: This review explores the development of NO-releasing nanoparticles that provide a controlled, targeted delivery system for NO, enhancing its antimicrobial efficacy while minimizing toxicity. The review discusses various NO donors, nanoparticle platforms, and how NO disrupts biofilm formation and eradicates pathogens. Additionally, we examine the highly encouraging and inspiring results of NO-releasing nanoparticles against multidrug-resistant strains and their applications in medical and environmental contexts. This review highlights the promising role of NO-based nanotechnologies in overcoming the challenges posed by increasing antibiotic resistance and biofilm-associated infections. Conclusions: Although NO donors and nanoparticle delivery systems show great potential for antimicrobial and anti-biofilm uses, addressing challenges related to controlled release, toxicity, biofilm penetration, resistance, and clinical application is crucial.