Targeting the small intestine employing nanotechnology has proved to be a more effective way for site-specific drug delivery. The drug targeting to the small intestine can be achieved via nanoparticles for its optimum bioavailability within the systemic circulation. The small intestine is a remarkable candidate for localized drug delivery. The intestine has its unique properties. It has a less harsh environment than the stomach, provides comparatively more retention time, and possesses a greater surface area than other parts of the gastrointestinal tract. This review focuses on elaborating the intestinal barriers and approaches to overcome these barriers for internalizing nanoparticles and adopting different cellular trafficking pathways. We have discussed various factors that contribute to nanocarriers' cellular uptake, including their surface chemistry, surface morphology, and functionalization of nanoparticles. Furthermore, the fate of nanoparticles after their uptake at cellular and subcellular levels is also briefly explained. Finally, we have delineated the strategies that are adopted to determine the cytotoxicity of nanoparticles.
Addressing poor solubility and permeability issues associated with synthetic drugs and naturally occurring active compounds is crucial for improving bioavailability. This review explores the potential of phospholipid complex formulation technology to overcome these challenges. Phospholipids, as endogenous molecules, offer a viable solution, with drugs complexed with phospholipids demonstrating a similar absorption mechanism. The non-toxic and biodegradable nature of the phospholipid complex positions it as an ideal candidate for drug delivery. This article provides a comprehensive exploration of the mechanisms underlying phospholipid complexes. Special emphasis is placed on the solvent evaporation method, with meticulous scrutiny of formulation aspects such as the phospholipid ratio to the drug and solvent. Characterization techniques are employed to understand structural and functional attributes. Highlighting the adaptability of the phospholipid complex, the review discusses the loading of various nanoformulations and emulsion systems. These strategies aim to enhance drug delivery and efficacy in various malignancies, including breast, liver, lung, cervical, and pancreatic cancers. The broader application of the drug phospholipid complex is showcased, emphasizing its adaptability in diverse oncological settings. The review not only explores the mechanisms and formulation aspects of phospholipid complexes but also provides an overview of key clinical studies and patents. These insights contribute to the intellectual and translational advancements in drug phospholipid complexes.
Perianal mucinous adenocarcinoma (PMA) is an oncologic rarity that poses a diagnostic and therapeutic dilemma for treating clinicians because there are few reported cases and an absence of definitive guidelines. We report a patient who had been treated with local surgery for recurrent perianal abscess with fistula for 3 years. Biopsy of the indurated tissue overlying his surgical scars revealed PMA. Neoadjuvant concurrent chemoradiotherapy followed by abdominoperineal resection was planned to address the locally advanced disease and ongoing sepsis. Our case is unique in that the fistula preceded carcinoma by only 3 years instead of the typical 10 years.
Gold nanoparticles (AuNPs) have undergone significant research for their use in the treatment of cancer. Numerous researchers have established their potent antitumor properties, which have greatly impacted the treatment of cancer. AuNPs have been used in four primary anticancer treatment modalities, namely radiation, photothermal therapy, photodynamic therapy, and chemotherapy. However, the ability of AuNPs to destroy cancer is lacking and can even harm healthy cells without the right direction to transport them to the tumor microenvironment. Consequently, a suitable targeting technique is needed. Based on the distinct features of the human tumor microenvironment, this review discusses four different targeting strategies that target the four key features of the tumor microenvironment, including abnormal vasculature, overexpression of specific receptors, an acidic microenvironment, and a hypoxic microenvironment, to direct surface-functionalized AuNPs to the tumor microenvironment and increase antitumor efficacies. In addition, some current completed or ongoing clinical trials of AuNPs will also be discussed below to further reinforce the concept of using AuNPs in anticancer therapy.
Recently, transdermal monitoring and drug delivery have gained much interest, owing to the introduction of the minimally invasive microneedle (MN) device. The advancement of electroactive MNs electrically assisted in the capture of biomarkers or the triggering of drug release. Recent works have combined conducting polymers (CPs) onto MNs owing to the soft nature of the polymers and their tunable ionic and electronic conductivity. Though CPs are reported to work safely in the body, their biocompatibility in the skin has been insufficiently investigated. Furthermore, during electrical biasing of CPs, they undergo reduction or oxidation, which in practical terms leads to release/exchange of ions, which could pose biological risks. This work investigates the viability and proliferation of skin cells upon exposure to an electrochemically biased MN pair comprising two differently doped poly(3,4-ethylenedioxy-thiophene) (PEDOT) polymers that have been designed for skin sampling use. The impact of biasing on human keratinocytes and dermal fibroblasts was determined at different initial cell seeding densities and incubation periods. Indirect testing was employed, whereby the culture media was first exposed to PEDOTs prior to the addition of this extract to cells. In all conditions, both unbiased and biased PEDOT extracts showed no cytotoxicity, but the viability and proliferation of cells cultured at a low cell seeding density were lower than those of the control after 48 h of incubation.
Calcium silicate (CaSiO3, CS) ceramics are promising bioactive materials for bone tissue engineering, particularly for bone repair. However, the low toughness of CS limits its application in load-bearing conditions. Recent findings indicating the promising biocompatibility of graphene imply that graphene can be used as an additive to improve the mechanical properties of composites. Here, we report a simple method for the synthesis of calcium silicate/reduced graphene oxide (CS/rGO) composites using a hydrothermal approach followed by hot isostatic pressing (HIP). Adding rGO to pure CS increased the hardness of the material by ∼40%, the elastic modulus by ∼52%, and the fracture toughness by ∼123%. Different toughening mechanisms were observed including crack bridging, crack branching, crack deflection, and rGO pull-out, thus increasing the resistance to crack propagation and leading to a considerable improvement in the fracture toughness of the composites. The formation of bone-like apatite on a range of CS/rGO composites with rGO weight percentages ranging from 0 to 1.5 has been investigated in simulated body fluid (SBF). The presence of a bone-like apatite layer on the composite surface after soaking in SBF was demonstrated by X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM). The biocompatibility of the CS/rGO composites was characterized using methyl thiazole tetrazolium (MTT) assays in vitro. The cell adhesion results showed that human osteoblast cells (hFOB) can adhere to and develop on the CS/rGO composites. In addition, the proliferation rate and alkaline phosphatase (ALP) activity of cells on the CS/rGO composites were improved compared with the pure CS ceramics. These results suggest that calcium silicate/reduced graphene oxide composites are promising materials for biomedical applications.
Guided bone regeneration (GBR) scaffolds are futile in many clinical applications due to infection problems. In this work, we fabricated GBR with an anti-infective scaffold by ornamenting 2D single crystalline bismuth-doped nanohydroxyapatite (Bi-nHA) rods onto segmented polyurethane (SPU). Bi-nHA with high aspect ratio was prepared without any templates. Subsequently, it was introduced into an unprecedented synthesized SPU matrix based on dual soft segments (PCL-b-PDMS) of poly(ε-caprolactone) (PCL) and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, undoped pristine nHA rods were also ornamented into it. The enzymatic ring-opening polymerization technique was adapted to synthesize soft segments of PCL-b-PDMS copolymers of SPU. Structure elucidation of the synthesized polymers is done by nuclear magnetic resonance spectroscopy. Sparingly, Bi-nHA ornamented scaffolds exhibit tremendous improvement (155%) in the mechanical properties with excellent antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast cells (in vitro), the scaffolds were implanted in rabbits by subcutaneous and intraosseous (tibial) sites. Various histological sections reveal the signatures of early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks of the critical defects filled with ornamented scaffold compared to SPU scaffold. This implies osteogenic potential and ability to provide an adequate biomimetic microenvironment for mineralization for GBR of the scaffolds. Organ toxicity studies further confirm that no tissue architecture abnormalities were observed in hepatic, cardiac, and renal tissue sections. This finding manifests the feasibility of fabricating a mechanically adequate nanofibrous SPU scaffold by a biomimetic strategy and the advantages of Bi-nHA ornamentation in promoting osteoblast phenotype progression with microbial protection (on-demand) for GBR applications.
Thin-film lithium-ion microbatteries with a high energy density and long lifespan are exceedingly desired for developing self-powered integrated micro-nano devices and systems. However, exploring high-performance thin-film anodes still remains a challenge. Herein, a double-layer-structure diamond-like carbon-ZnS (DLC-ZnS) thin-film anode fabricated by radio frequency magnetron sputtering exhibits high specific capacity and good cycling stability up to 1000 cycles, superior to the pure ZnS thin-film anode. To understand the mechanism, the bimodal amplitude modulated-frequency modulated atomic force microscopy was used to explore the mechanical properties of the thin films, and the DLC layer shows significantly higher Young's modulus than the ZnS thin film. The DLC interface with a high Young's modulus can effectively buffer the mechanical stress originating from the huge volume changes of the ZnS layer during lithiation/delithiation processes; therefore, the DLC interface maintains the higher mechanical integrity of the DLC-ZnS thin film and improves the utilization of ZnS. In addition, the electrochemical kinetics of the DLC-ZnS and ZnS thin films were also investigated by electrochemical methods. Electrochemical impedance spectroscopy tests indicate the obstacle of the DLC interface to Li+ ion diffusion in the initial charge/discharge processes; however, the DLC-ZnS thin film exhibits lower total resistance than the ZnS thin film afterward. In particular, galvanostatic intermittent titration technique tests were performed to find out the differences between the two thin films during the galvanostatical charge/discharge processes. The results demonstrate the obviously enhanced conversion reaction reversibility and decreased alloy reaction polarization of the DLC-ZnS thin film; therefore, it delivers higher reversible capacity.
Clinical translation of nanotechnologies has limited success, at least in part, due to the existence of several overlooked factors on the nature of the nanosystem (e.g., physicochemical properties of nanoparticles), nanobio interfaces (e.g., protein corona composition), and the cellular characteristics (e.g., cell type). In the past decade, several ignored factors including personalized and disease-specific protein corona (a layer of formed biomolecules at the surface of nanoparticles upon their entrance into a biological fluid), incubating temperature, local temperature gradient, cell shape, and cell sex has been introduced. Here, it was hypothesized and validated cell age as another overlooked factor in the field of nanomedicine. To test our hypothesis, cellular toxicity and uptake profiles of our model nanoparticles (i.e., PEGylated quantum dots, QDs) were probed in young and senescent cells (i.e., IMR90 fibroblast cells from human fetal lung and CCD841CoN epithelial cells from human fetal colon) and the outcomes revealed substantial dependency of cell-nanoparticles interactions to the cell age. For example, it was observed that the PEGylated QDs were acutely toxic to senescent IMR90 and CCD841CoN cells, leading to lysosomal membrane permeabilization which caused cell necrosis; in contrast, the young cells were resilient to the exact same amount of QDs and the same incubation time. It was also found that the formation of protein corona could delay the QDs' toxicity on senescent cells. These findings suggest that the cellular aging process have a capacity to cause deteriorative effects on their organelles and normal functions. The outcomes of this study suggest the proof-of-concept that cell age may have critical role in biosystem responses to nanoparticle technologies. Therefore, the effect of cell age should be carefully considered on the nanobio interactions and the information about cellular age (e.g., passage number and age of the cell donor) should be included in the nanomedicine papers to facilitate clinical translation of nanotechnologies and to help scientists to better design and produce safe and efficient diagnostic/therapeutic age-specific nanoparticles.
Abraxane, an albumin-bound paclitaxel nanoparticle formulation, is superior to conventional paclitaxel preparations because it has better efficacy against unresectable pancreatic cancer. Previous reports suggest that this better efficacy of Abraxane than conventional paclitaxel preparation is probably due to its transport through Gp60, an albumin receptor on the surface of vascular endothelial cells. The increased tumor accumulation of Abraxane is also caused by the secreted protein acid and rich in cysteine in the tumor stroma. However, the uptake mechanism of Abraxane remains poorly understood. In this study, we demonstrated that the delivery of Abraxane occurred via different receptor pathways from that of endogenous albumin. Our results showed that the uptake of endogenous albumin was inhibited by a Gp60 pathway inhibitor in the process of endocytosis through endothelial cells or tumor cells. In contrast, the uptake of Abraxane-derived HSA was less affected by the Gp60 pathway inhibitor but significantly reduced by denatured albumin receptor inhibitors. In conclusion, these data indicate that Abraxane-derived HSA was taken up into endothelial cells or tumor cells by a mechanism different from normal endogenous albumin. These new data on distinct cellular transport pathways of denatured albumin via gp family proteins different from those of innate albumin shed light on the mechanisms of tumor delivery and antitumor activity of Abraxane and provide new scientific rationale for the development of a novel albumin drug delivery strategy via a denatured albumin receptor.
Tissue engineering aims to generate or facilitate regrowth or healing of damaged tissues by applying a combination of biomaterials, cells, and bioactive signaling molecules. In this regard, growth factors clearly play important roles in regulating cellular fate. However, uncontrolled release of growth factors has been demonstrated to produce severe side effects on the surrounding tissues. In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) incorporated three-dimensional (3D) CORAGRAF scaffolds were engineered to achieve controlled release of platelet-derived growth factor-BB (PDGF-BB) for the differentiation of stem cells within the 3D polymer network. Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, scanning electron microscopy, and microtomography were applied to characterize the fabricated scaffolds. In vitro study revealed that the CORAGRAF-PLGA-PDGF-BB scaffold system enhanced the release of PDGF-BB for the regulation of cell behavior. Stromal cell attachment, viability, release of osteogenic differentiation markers such as osteocalcin, and upregulation of osteogenic gene expression exhibited positive response. Overall, the developed scaffold system was noted to support rapid cell expansion and differentiation of stromal cells into osteogenic cells in vitro for bone tissue engineering applications.
The evaluation of the interaction of cells with biomaterials is fundamental to establish the suitability of the biomaterial for a specific application. In this study, the properties of bacterial nanocellulose/acrylic acid (BNC/AA) hydrogels fabricated with varying BNC to AA ratios and electron-beam irradiation doses were determined. The manner these hydrogel properties influence the behavior of human dermal fibroblasts (HDFs) at the cellular and molecular levels was also investigated, relating it to its application both as a cell carrier and wound dressing material. Swelling, hardness, adhesive force (wet), porosity, and hydrophilicity (dry) of the hydrogels were dependent on the degree of cross-linking and the amount of AA incorporated in the hydrogels. However, water vapor transmission rate, pore size, hydrophilicity (semidry), and topography were similar between all formulations, leading to a similar cell attachment and proliferation profile. At the cellular level, the hydrogel demonstrated rapid cell adhesion, maintained HDFs viability and morphology, restricted cellular migration, and facilitated fast transfer of cells. At the molecular level, the hydrogel affected nine wound-healing genes (IL6, IL10, MMP2, CTSK, FGF7, GM-CSF, TGFB1, COX2, and F3). The findings indicate that the BNC/AA hydrogel is a potential biomaterial that can be employed as a wound-dressing material to incorporate HDFs for the acceleration of wound healing.
Chitosan-based hemostats are promising candidates for immediate hemorrhage control. However, they have some disadvantages and require further improvement to achieve the desired hemostatic efficiency. Here, a series of 1% Ga2O3-containing mesoporous bioactive glass-chitosan composite scaffolds (Ga-MBG/CHT) were constructed by the lyophilization process and the effect of various concentrations of Ga-MBG (10, 30, and 50 wt %) on the hemostatic function of the CHT scaffold was assessed as compared to that of Celox Rapid gauze (CXR), a current commercially available chitosan-coated hemostatic gauze. The prepared scaffolds exhibited >79% porosity and showed increased water uptake compared to that in CXR. The results of coagulation studies showed that pure CHT and composite scaffolds exhibited increased hemostatic performance with respect to CXR. Furthermore, the composite scaffold with the highest Ga-MBG content (50 wt %) had increased capability to enhancing thrombus generation, blood clotting, and platelet adhesion and aggregation than that of the scaffold made of pure CHT. The antibacterial efficacy and biocompatibility of the prepared scaffolds were also assessed by a time-killing assay and an Alamar Blue assay, respectively. Our results show that the antibacterial effect of 50% Ga-MBG/CHT was more pronounced than that of CHT and CXR. The cell viability results also demonstrated that Ga-MBG/CHT composite scaffolds had good biocompatibility, which facilitates the spreading and proliferation of human dermal fibroblast cells even with 50 wt % Ga-MBG loading. These results suggest that Ga-MBG/CHT scaffolds could be a promising hemostatic candidate for improving hemostasis in critical situations.
Nanomedicines, while having been approved for cancer therapy, present many challenges such as low stability, rapid clearance, and nonspecificity leading to off-target toxicity. Cubosomes are porous lyotropic liquid crystalline nanoparticles that have shown great premise as drug delivery vehicles; however, their behavior in vivo is largely underexplored, hindering clinical translation. Here, we have engineered cubosomes based on the space group Im3m that are loaded with copper acetylacetonate as a model drug, and their surfaces are functionalized for the first time with Affimer proteins via copper-free click chemistry to actively target overexpressed carcinoembryonic antigens on LS174T colorectal cancer cells. Unlike nontargeted cubosomes, Affimer tagged cubosomes showed preferential accumulation in cancer cells compared to normal cells not only in vitro (2D monolayer cell culture and 3D spheroid models) but also in vivo in colorectal cancer mouse xenografts, while exhibiting low nonspecific absorption and toxicity in other vital organs. Cancerous spheroids had maximum cell death compared to noncancerous cells upon targeted delivery. Xenografts subjected to targeted drug-loaded cubosomes showed a 5-7-fold higher drug accumulation in the tumor tissue compared to the liver, kidneys, and other vital organs, a significant decrease in tumor growth, and an increased survival rate compared to the nontargeted group. This work encompasses the first thorough preclinical investigation of Affimer targeted cubosomes as a cancer therapeutic.
Spinal cord injury (SCI) causes severe motor or sensory damage that leads to long-term disabilities due to disruption of electrical conduction in neuronal pathways. Despite current clinical therapies being used to limit the propagation of cell or tissue damage, the need for neuroregenerative therapies remains. Conductive hydrogels have been considered a promising neuroregenerative therapy due to their ability to provide a pro-regenerative microenvironment and flexible structure, which conforms to a complex SCI lesion. Furthermore, their conductivity can be utilized for noninvasive electrical signaling in dictating neuronal cell behavior. However, the ability of hydrogels to guide directional axon growth to reach the distal end for complete nerve reconnection remains a critical challenge. In this Review, we highlight recent advances in conductive hydrogels, including the incorporation of conductive materials, fabrication techniques, and cross-linking interactions. We also discuss important characteristics for designing conductive hydrogels for directional growth and regenerative therapy. We propose insights into electrical conductivity properties in a hydrogel that could be implemented as guidance for directional cell growth for SCI applications. Specifically, we highlight the practical implications of recent findings in the field, including the potential for conductive hydrogels to be used in clinical applications. We conclude that conductive hydrogels are a promising neuroregenerative therapy for SCI and that further research is needed to optimize their design and application.
Nanotechnology has emerged as a transformative pathway in vaccine research and delivery. Nanovaccines, encompassing lipid and nonlipid formulations, exhibit considerable advantages over traditional vaccine techniques, including enhanced antigen stability, heightened immunogenicity, targeted distribution, and the potential for codelivery with adjuvants or immune modulators. This review provides a comprehensive overview of the latest advancements and applications of lipid and non-lipid-based nanovaccines in current vaccination strategies for immunization. The review commences by outlining the fundamental concepts underlying lipid and nonlipid nanovaccine design before delving into the diverse components and production processes employed in their development. Subsequently, a comparative analysis of various nanocarriers is presented, elucidating their distinct physicochemical characteristics and impact on the immune response, along with preclinical and clinical studies. The discussion also highlights how nanotechnology enables the possibility of personalized and combined vaccination techniques, facilitating the creation of tailored nanovaccines to meet the individual patient needs. The ethical aspects concerning the use of nanovaccines, as well as potential safety concerns and public perception, are also addressed. The study underscores the gaps and challenges that must be overcome before adopting nanovaccines in clinical practice. This comprehensive analysis offers vital new insights into lipid and nonlipid nanovaccine status. It emphasizes the significance of continuous research, collaboration among interdisciplinary experts, and regulatory measures to fully unlock the potential of nanotechnology in enhancing immunization and ensuring a healthier, more resilient society.
γ-Secretase inhibitors (GSIs) and modulators (GSMs) are at the frontline of cancer and Alzheimer's disease research, respectively. While both are therapeutically promising, not much is known about their interactions with proteins other than γ-secretase. Signal peptide peptidase (SPP), like γ-secretase, is a multispan transmembrane aspartyl protease that catalyzes regulated intramembrane proteolysis. We used active site-directed photophore walking probes to study the effects of different GSIs and GSMs on the active sites of γ-secretase and SPP and found that nontransition state GSIs inhibit labeling of γ-secretase by activity-based probes but enhance labeling of SPP. The opposite is true of GSMs, which have little effect on the labeling of γ-secretase but diminish labeling of SPP. These results demonstrate that GSIs and GSMs are altering the structure of not only γ-secretase but also SPP, leading to potential changes in enzyme activity and specificity that may impact the clinical outcomes of these molecules.
SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4 interact with inducible nitric oxide synthase (iNOS), causing the iNOS to be polyubiquitinated and targeted for degradation. Inhibition of this interaction increases iNOS levels, and consequently cellular nitric oxide (NO) concentrations, and has been proposed as a potential strategy for killing intracellular pathogens. We previously described two DINNN-containing cyclic peptides (CP1 and CP2) as potent inhibitors of the murine SPSB-iNOS interaction. In this study, we report the crystal structures of human SPSB4 bound to CP1 and CP2 and human SPSB2 bound to CP2. We then used these structures to design a new inhibitor in which an intramolecular hydrogen bond was replaced with a hydrocarbon linkage to form a smaller macrocycle while maintaining the bound geometry of CP2 observed in the crystal structures. This resulting pentapeptide SPSB-iNOS inhibitor (CP3) has a reduced macrocycle ring size, fewer nonbinding residues, and includes additional conformational constraints. CP3 has a greater affinity for SBSB2 ( KD = 7 nM as determined by surface plasmon resonance) and strongly inhibits the SPSB2-iNOS interaction in macrophage cell lysates. We have also determined the crystal structure of CP3 in complex with human SPSB2, which reveals the structural basis for the increased potency of CP3 and validates the original design.
Glioblastoma multiforme (GBM), a standout among the most dangerous class of central nervous system (CNS) cancer, is most common and is an aggressive malignant brain tumor in adults. In spite of developments in modality therapy, it remains mostly incurable. Consequently, the need for novel systems, strategies, or therapeutic approaches for enhancing the assortment of active agents meant for GBM becomes an important criterion. Currently, cancer research focuses mainly on improving the treatment of GBM via diverse novel drug delivery systems. The treatment options at diagnosis are multimodal and include radiation therapy. Moreover, significant advances in understanding the molecular pathology of GBM and associated cell signaling pathways have opened opportunities for new therapies. Innovative treatment such as immunotherapy also gives hope for enhanced survival. The objective of this work was to collect and report the recent research findings to manage GBM. The present review includes existing novel drug delivery systems and therapies intended for managing GBM. Reported novel drug delivery systems and diverse therapies seem to be precise, secure, and relatively effective, which could lead to a new track for the obliteration of GBM.
Naegleria fowleri (N. fowleri) causes primary amoebic meningoencephalitis (PAM) which almost always results in death. N. fowleri is also known as "brain-eating amoeba" due to its literal infestation of the brain leading to an inflammatory response in the brain tissues. Currently, there is no single drug that is available to treat PAM, and most treatments are combinations of antifungal, anticancer, and anti-inflammatory drugs. Recently nanotechnology has gained attention in chemotherapeutic research converging on drug delivery, while oleic acid (OA) has shown positive effects on the human immune system and inflammatory processes. In continuation of our recent research in which we reported the effects of oleic acid conjugated with silver nanoparticles (OA-AgNPs) against free-living amoeba Acanthamoeba castellanii, in this report, we show their antiamoebic effects against N. fowleri. OA alone and its nanoconjugates were tested against the amoeba by using amoebicidal and host cell cytopathogenicity assays. Trypan blue exclusion assay was used to determine cell viability. The results revealed that OA-AgNPs exhibited significantly enhanced antiamoebic effects (P < 0.05) against N. fowleri as compared to OA alone. Evidently, lactate dehydrogenase release shows reduced N. fowleri-mediated host cell cytotoxicity. Based on our study, we anticipate that further studies on OA-AgNPs could potentially provide an alternative treatment of PAM.