Nanomedicine Journal
Volume:12 Issue: 2, Spring 2025

Graphene and its derived forms have surfaced as promising substances for a wide range of technological and biomedical purposes. However, it is crucial to evaluate their safety and potential risks to ensure their safe use. This systematic review examines the present state of knowledge regarding the toxicity of graphene oxide (GO) through in-vivo, in-vitro, and other species studies. The aim of this present research was to study toxicity outcomes of GO-coated materials. The literature search was conducted and most important electronic databases (20 studies) were checked and selected for the present study. The findings underscore the need for cautious consideration of GO’s potential risks, especially at high concentrations and prolonged exposures. Continued research efforts are essential to gain a deeper understanding of the underlying mechanisms and to develop appropriate safety guidelines for the utilization of GO in various applications.

Persistent clinical infections have driven extensive research to find effective solutions. Liposomes, known for their biocompatibility, versatility, targetability, and tunability, have emerged as a prominent drug delivery system. They enhance the delivery of contemporary antibiotics to resistant infections and facilitate the introduction of a wide range of novel antimicrobial agents.

This review adopts a systematic and thematic approach to encompass all studies involving liposomal antimicrobials for biofilm-producing infections. Original papers were retrieved from NCBI/PubMed using MeSH terms ‘liposome’, ‘antimicrobial’, and ‘biofilm’. An inductive qualitative thematic analysis was then conducted to identify the main themes and sub-themes. Themes supporting the primary objective and fundamentals were included, while those covered in previous reviews were excluded.

Liposomes are an exceptional delivery system for treating clinical biofilm infections. They improve the delivery of contemporary hydrophobic antibiotics and enable the combinatorial introduction of natural and synthetic antimicrobials. Liposomes also serve as a suitable platform for controlled drug release, physicochemical modification, and surface functionalization with various biological ligands. Additionally, they allow for modifications that enhance adhesion to biotic and abiotic surfaces and support extended, prolonged drug release profiles with implants, scaffolds, and hydrogels.

Given their ease of manipulation and modulation, liposomes are anticipated to remain a long-standing drug delivery platform in future research focused on treating persistent infections with antimicrobials.

Researchers have successfully developed and validated diverse loading strategies, utilizing both endogenous and exogenous approaches, in laboratory and animal models, showcasing their effectiveness in advancing molecular biology research. Extracellular vesicles have advantages over synthetic carriers in disease management and therapeutics. However, their clinical application is hindered by challenges such as limited specificity, low production yield, storage stability, and targeting capability. Addressing these challenges and exploring exosome engineering techniques is crucial. Cell-derived exosomes can serve as carriers for therapeutic molecules, enabling targeted drug delivery. Understanding exosome formation and developing efficient engineering methods are essential for advancing clinical therapeutic strategies. Exosomes offer a unique approach to targeted drug delivery through intercellular communication. These natural liposomes carry endogenous biomolecules, ensuring biocompatibility and allowing for cargo loading. Genetic or chemical modifications can improve targeting and drug loading capabilities. Importantly, exosomes have weak interactions with serum proteins, extending the lifespan of the cargo. By combining the capabilities of artificial nanocarriers and intercellular signaling, exosomes provide new and reliable strategies for drug administration and medical interventions. This review examines diverse exosome types, preparation methodologies, cargo encapsulation, and their efficacy in delivering therapeutic agents across different diseases. It also highlights global companies involved in the development and testing of exosome-based therapies.

Recently, magnetic nanoparticles coated with different ligands have been utilized in diagnosis, drug delivery, and therapy. This study aimed to synthesize,  characterize, and apply Fe3O4 coated with Poly Dopamine (PDA) as an MR imaging nanoprobe and its application in metronidazole-resistant helicobacter pylori (H.pylori).

Fe3O4 nanoparticles were characterized and their cytotoxicity was determined in MCF-7 cell lines. Then, coated and non-coated nanoparticles were injected intravenously into  9 xenograft BALB/C mice, and the signal intensity of the T2-weighted MR was assessed. Iron concentrations were measured by ICP-AES, and histopathological assessment was done on harvested critical organs. Finally, The standard disk diffusion method was also used to identify the H.pylori resistance to metronidazole. The minimum inhibitory concentrations and the minimum bactericidal concentration of uncoated and coated iron oxide nanoparticles were investigated.

The MTT assay showed low cytotoxicity at 512 µg/ml. T2 relaxation times of tumors were lower compared to normal tissues. ICP-AES results indicated that the NPs accumulated mostly in the spleen and liver. The histopathology study demonstrated that the vital organ tissues had less morphologic abnormality and apoptotic changes. The minimum inhibitory and minimum bactericidal concentrations of ION@PDA were 16-64 µg/ml and 16-128 µg/ml, respectively. 

Due to the high permeability of nanoprobes in tumors, less cytotoxicity, and its inhibitory effects on metronidazole-resistant H.pylori, ION@PDA may be used as a nano contrast agent in MR imaging for the detection of MCF-7 cells.

Traditional wound dressings primarily promote passive wound healing and infrequently promote active wound healing by influencing skin cell. It is known that electrical stimulation (ES) can control the actions of skin cells. In the present study, the conductive electrospun PU/rGO was designed and fabricated and its qualities as skin wound dressings in animal models were examined. 

In this study, nanocomposite PU (polyurethane)/rGO (reduce graphene oxide) was synthesized using an electrospinning process, investigated via scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), water contact angle, degradation studies, electrochemical impedance spectroscopy (EIS), bactericidal efficacy, hemolysis and MTT assay.  Then, the scaffolds were grafted in full-thickness wounds of animal rats and evaluated by wound closure and histological.

The results showed that the PU/rGO scaffold exhibited antibacterial activity in comparison with PU scaffold and viability showed a notable improvement in cell promotion. In the histopathological analysis, improved dermis development and collagen deposition at the healed wound area of the PU/rGO scaffold with electrical stimulation in comparison to other groups were observed. 

A PU/rGO scaffold with electrical stimulation could be an appropriate option for skin tissue engineering and wound healing.

The clinical application of doxorubicin (DOX), a potent anticancer agent, is restricted by its serious side-effects and multidrug resistance. The combination strategy of antineoplastic drugs with Berberine (BBR) as plant-derived natural products enhances the cytotoxicity of chemotherapeutic drugs in cancer cells and also amends their toxicity in normal cells. 

In this study, the nanoparticles (NPs) of PLGA/PVA containing DOX and BBR were synthesized and optimized using the double emulsion-solvent evaporation method. The vesicular size, zeta potential, entrapment efficiency and also the drug release profile was surveyed at different temperatures and pH (37 °C, 7.4 and 42 °C, 5.2). The MTT assay was used to evaluate the cytotoxic effects of individual of DOX and BBR as a free form and as a nanoparticle form and also the combination of DOX- and BBR-loaded NPs on MCF-7 breast cancer cells. 

The optimum formulation demonstrated that the vesicle size and zeta potential of DOX were 176.4 nm and -56.4 mV and BBR were 150.3 nm and -41.2 mV, respectively. Entrapment efficiency (EE%) for DOX and BBR was 91.0 ± 1.9% and 82.0 ± 1.8%, respectively. The DOX- and BBR -loaded NPs exhibited a sustained and controlled release pattern with the pH- and thermosensitive characteristic. Additionally, the loading of DOX and BBR into PLGA/PVA NPs had a higher toxicity against cancer cells when compared with free forms and the combination of DOX and BBR was exhibited an augmented antineoplastic activity against the cancer cell death. 

The findings of this study suggest that the coadministration of DOX with BBR using the PLGA/PVA NPs may have the potential clinical application in sensitization cells to DOX and generates synergistic antitumor effects.

Acute myocardial infarction causes the heart to lose its proper function due to contractile dysfunction within the damaged ischemic cardiac tissue. Different studies have presented various cardiac patches based on different biomaterials to support the infarcted myocardium to recover cardiac function. 

In this study, we developed a nanofiber cardiac patch with antioxidant and antibacterial properties. Polycaprolactone (PCL) nanofibers were enriched with chitosan-coated selenium nanoparticles (Cs-SeNPs) using an electrospinning technique. 

The PCL/Cs-SeNPs nanofibers, with an average diameter of 648.36±259.19 nm, displayed antioxidant properties in the DPPH assay. Additionally, viable cell count assessment demonstrated the antibacterial effects of PCL/Cs-SeNPs nanofibers against Staphylococcus aureus and Escherichia coli bacteria. MTT assay results revealed improved proliferation for the PCL/Cs-SeNPs nanofibers compared to the PCL nanofibers scaffold, with no significant cell toxicity. The SEM imaging and DAPI/Phalloidin staining supported the improved cell adhesion with well-expanded cytoskeleton of 3T3 cells on PCL/Cs-SeNPs nanofibers. In the rat model of myocardial infarction, improved cardiac function and reduced post-surgical adhesion were observed 28 days after surgery. 

The results of this study suggest that the PCL/Cs-SeNPs nanofibers cardiac patch can be considered a potent supportive strategy for myocardial rehabilitation after myocardial infarction.

In a new approach, copper(II) oxide (CuO) nanostructure was synthesized by a solvothermal method for applying as a biosensor for detecting of glucose. Determination of the glucose is important in controlling of diabetes. Non-enzymatic detection of glucose is preferable because of its low cost benefits. Otherwise, CuO can play a role in oxidation of glucose to gluconic acid which is important in glucose detection. Therefore, obtaining new morphology or new composite from CuO is interesting. 

CuO nanostructure was prepared with the assistance of a bifunctional amino acid of L-lysine (with the isoelectric point about 10 for precipitating copper ion) and an additive of urea. Fourier transform infrared (FT-IR) and Raman spectroscopies, X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), cyclic voltammetry analyses and differential pulse voltammetry (DPV) were employed.

XRD indicated that the synthesized CuO consists of a tenorite crystal system with a monoclinic structure. The TEM histogram showed a mean diameter of 91 nm for CuO nanostructure. CuO nanostructure loaded on graphene oxide-grafted Lisdexamfetamine Dimesylate (LIS) to achieve CuO/LIS-g-GO composite. CuO/LIS-g-GO was dropped on a glassy carbon electrode (GCE) to develop a new nanobiosensor for detecting glucose in a cost-effective manner without the necessity of using glucose oxidase or nafion. Phosphate buffer (PBS) and simulated body fluid (SBF) solutions were the media of the glucose detection. The sensitivity of the biosensor was 34.7 µA/cm2mM for 10 mM concentration of the glucose. The mentioned sensor detected no interference in the presence of dopamine and fructose. Also, the repeatability of the biosensor was investigated and the measured standard deviation (RSD) was 3.93%.

New nanostructured CuO was composited with LIS-g-GO and the new biosensor of CuO/LIS-g-GO/GCE was applied for the detection of glucose. The sensitivity of 34.7 µA/cm2mM without any interference of dopamine and fructose caused this system as favorite sensor for the detection of glucose.

The mucoadhesive systems are among the preferred dosage forms for oral disorders. They can be designed to concentrate the drug at the site of action, control the drug release, and reduce both the frequency of medication and the systemic side effects. This study aims to design and evaluate a multilayered oro-mucoadhesive film encompassing chamomile hydroalcoholic extract and Lidocaine to manage oral aphthous disorder. 

A three-layer film for controlled release of Lidocaine and chamomile extract was prepared stepwise. The solvent casting method was used to prepare the fast-dissolving layer containing Lidocaine and chitosan/eudragit® S100 mucoadhesive layers. The middle layer, i.e. polycaprolactone nanofiber loaded with chamomile hydroalcoholic extract, was prepared by electrospinning. Layers were evaluated for appearance, thickness, pH, mucoadhesion, folding endurance, swellability, film disintegration time, content uniformity, chemical structure, and drug release. By attaching layers, the final system was prepared while DDSolver software was used to assess the release mechanism of Lidocaine and chamomile extract.

The final dosage form had desirable physicochemical features, including mucoadhesive strength. The entire Lidocaine was released by diffusion over the first 4 hours, while the extract reached its maximum cumulative release (%) after about 24 hours under a combined release mechanism of diffusion and polymer relaxation. 

Due to having polymers with different properties in each layer, our multilayered system allowed the controlled release of Lidocaine and chamomile extract, enabling it effectively used in the treatment of oral disorders.

 High levels of hydrogen peroxide (H2O2) induce oxidative stress in physiological environments. Elevation of H2O2 levels in semen can be a reason for male infertility, by causing protein and enzyme denaturation, lipid peroxidation, and DNA damage. Oxidative stress can affect sperm features, such as viability, motility, and fertilization potential. Although nanozymes are widely used to detect H2O2 using different techniques, monitoring of H2O2 in physiological fluids remains a challenge that has not been studied extensively. We report on a non-enzymatic paper strip based on γ-Fe2O3@Prussian blue nanoparticles (γ-Fe2O3@PB NPs) and their performance for H2O2 detection in buffer and seminal plasma. 

 γ-Fe2O3 NPs were synthesized using chemical coprecipitation method and were then coated with PB. γ-Fe2O3@PB NPs were characterized using ultraviolet-visible spectroscopy (UV-vis), dynamic light scattering (DLS), X-ray diffraction (XRD), and transmission electron microscopy (TEM). The results confirmed formation of relatively monodisperse and approximately 71 nm γ-Fe2O3@PB NPs. The peroxidase-like activities of γ-Fe2O3 NPs and γ-Fe2O3@PB NPs were measured using UV-visible spectroscopy. 

 The results demonstrated that the catalytic activity of  γ-Fe2O3@PB NPs was higher than that of γ-Fe 2 O3 NPs. The concentrations of γ-Fe2O3@PB NPs and TMB, immobilized on paper strips, were optimized. The detection limit of the constructed lateral flow assays (LFA) for H2O2 in acetate buffer was 50.0 µM. Citric acid and ascorbic acid, as common components in semen, showed interference with the performance of paper strips. The γ-Fe2O3@PB NPs-based paper strip could detect H2O2 spiked in human seminal plasma in 20 min with a detection limit of 750.0 µM. 

 The colorimetric detection of H2O2 on paper strips was successful and quantification of the results was possible with the help of a cell phone, which makes it a breakthrough in quantitative rapid tests.

Natural compounds, such as Oleuropein, Quercetin, Coumarin, and Valproic acid, play a vital role in preventing the spread and progression of cancer. Oleuropein increases the expression of certain caspases, Quercetin reduces the activity of the PI3K/Akt/IKK-/NF-κB pathway, Coumarin inhibits aromatase, and Valproic acid acts as an inhibitor of histone deacetylases. This study aimed to produce a quadruple magnetic nanocomplex with high bioavailability and to examine whether this nanocomplex can induce apoptosis in MCF7 breast cancer cell lines.

A silicon bridge (Sio-N-) was built using nanomagnetic iron and methoxysilane to create a magnetic nanocomplex that incorporated the four natural substances. This quadruple nanocomplex was then analyzed using various spectroscopic techniques and measurements. The researchers assessed the inhibitory impact of the nanocomplex on apoptotic genes in the MCF7 breast cancer cell line using the MTT assay, Hoechst staining, flow cytometry, and real-time PCR analysis.

The magnetic nanocomplex exhibited a greater level of toxicity and reduced the number of cancer cells compared to any of the individual natural compounds or the quadruple combination without nanoparticles. The quadruple magnetic nanocomplex induced overexpression of the pro-apoptotic genes P53, Bim, and Bak, while reducing the expression of the anti-apoptotic gene Bcl2. Additionally, the nanocomplex treatment increased the expression level of genes involved in apoptosis by up to two-fold.

The combination of plant-derived natural compounds and magnetic nanoparticles can enhance the toxicity and concentration of the materials against breast cancer cells. This approach may provide synergistic effects through the modulation of various molecular pathways, leading to the inhibition of cancer cell proliferation and the induction of apoptosis.

Recently, the use of tacrolimus in treating eye diseases has received much attention. Although this drug is powerful in treating eye diseases, however for various reasons, it lacks the necessary efficacy for multiple reasons. This research investigated the development of Tacrolimus encapsulated liposomes, optimization, loading effectiveness, increasing drug efficiency through absorption, controlled release, drug targeting, and reducing drug side effects such as nephropathy.

Two agents, liposome and chitosan, have been chosen to transport the drugs used in this study. Nanoliposomes were synthesized through the heating method and chitosan nanoparticles were by reversing the micelle method. A field emission scanning electron microscope(FESEM) was used to prepare images and a zeta sizer was used to measure the average size and distribution of particles. Drug release for 18 days was checked by in vitro and ex-vivo(Franz diffusion) tests. The MTT method was used to evaluate the cytotoxic effect of nanoparticles loaded with tacrolimus drug.

The molar ratio of the drug to liposome and chitosan was chosen to be 0.002. A drug loading effectiveness of (88-95%) was obtained. Tacrolimus drug loading efficiency in liposomes (EPC100, EPC80, DPPC60, DPPC100) value (88.95-95-74%) was obtained for its entrapment in liposome core with passive loading strategy. The difference in drug release rate for EPC 80/chitosan liposome and EPC 100/chitosan was 83.6% and 93.1%, respectively, and for DPPC60/chitosan and DPPC100/chitosan liposomes, 72.8% and 78.8%, respectively.

With this study, it can be concluded that DPPC liposome was good for drug loading. The results of the test (FT-IR) showed that the loading of the drug was successful. The results of electron microscope tests in both samples (EPC, DPPC) indicated the synthesis of drug delivery systems with a spherical morphology with a diameter of less than 100 nanometers. The release results showed that the highest release rate was related to EPC liposomes. In the MTT test, it was observed that nanocarriers without tacrolimus drugs do not show any toxic effect on cells.

Staphylococcus aureus is a common human pathogen that infects thousands of people every year. The growing resistance of this bacterium to antibiotics has increased the need for developing more effective and natural antimicrobial medications. In this study, niosomes loaded Rosmarinus officinalis (rosemary)@curcumin were synthesized, and their antimicrobial and anti-biofilm activity on clinical S. aureus strains was investigated. Rosmarinus officinalis (rosemary) extract was prepared through maceration and its compounds were identified by GC/MS. Niosomes loaded rosemary@curcumin were synthesized through thin-film hydration. Their characteristics were analyzed with dynamic light scattering (DLS)-zetasizer, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and drug release test was studied using a dialysis bag. Finally, the antimicrobial and anti-biofilm activity against clinical strains of S. aureus were investigated using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and crystal violet methods, respectively. Formulated niosomes were spherical, averaged 442 nm in size, and had uniform particle distribution. FTIR results indicated the successful encapsulation of rosemary@curcumin inside niosomes with 94.23% encapsulation efficiency. In vitro drug release studies showed a slow-release pattern of rosemary@curcumin from niosomes. The MIC and MBC values of niosomes loaded rosemary@curcumin were between 32.5 and 62.5 µg/ml and showed higher antimicrobial activity. Also, the results of the biofilm inhibition test showed that niosomes loaded rosemary@curcumin reduced the rate of biofilm formation between 2 and 4 fold. Niosomes loaded rosemary@curcumin have suitable structure and surface characteristics and can successfully inhibit S. aureus growth and prevent its biofilm formation potency.

Cancer remains a leading cause of mortality globally, necessitating novel and effective therapies. Nanotechnology, particularly poly (lactic-co-glycolic acid) (PLGA) nanoparticles, offers promising potential for safe and effective delivery of therapeutic agents due to their biocompatibility, biodegradability, and tunable release properties. This study aimed to synthesize PLGA nanoparticles loaded with auraptene (Aur-PLGA-NPs) and evaluate their anti-cancer effects.

Aur-PLGA-NPs were synthesized and characterized using particle size analyzer, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR). Cytotoxic effects were assessed against HT-29 colon cancer cells and human umbilical vein endothelial cells (HFF) as normal controls. Apoptotic mechanisms were investigated through 4,6-diamidino-2-phenylindole (DAPI) staining, flow cytometry, and gene expression analysis of caspase-3, caspase-9, and BAX.

Spherical nanoparticles with an average size of 185 nm were successfully synthesized. Aur-PLGA-NPs exhibited higher cytotoxicity against HT-29 cancer cells compared to HFF normal cells. Furthermore, Aur-PLGA-NPs significantly enhanced the expression of apoptotic genes caspase-3, caspase-9, and BAX in HT-29 cells.

The increased cytotoxicity of Aur-PLGA-NPs against cancer cells suggests their potential as anti-cancer agents. However, further studies are needed to evaluate their effects on other cancer cell lines and elucidate the underlying anti-cancer mechanisms.

Multidrug-resistant (MDR) organisms are posing threat by exhibiting resistance to commonly used antibiotics. From our study, we found a novel strategy to enhance the efficacy of antibiotics, which could help in treating diseases caused by various pathogens. We have used a natural, low-cost, biological reducing and capping agent, Thespesia populnea leaf extract to synthesize silver nanoparticles (AgNPs) and linezolid-conjugated silver nanoparticles (Li-AgNPs).

The nanoparticles were characterized by UV-visible spectroscopy, Scanning Electron Microscope (SEM), X-Ray Diffraction (XRD), and Fourier Transform Infrared (FT-IR) spectroscopy. The antimicrobial activity was evaluated against MDR Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium by agar well plate method. The UV-visible absorption spectra showed absorption peaks at 442 nm and 464 nm for AgNPs and Li-AgNPs, respectively. 

The SEM analysis revealed particle size with a diameter ranging from 18 to 22 nm and 24 to 32 nm, respectively, and spherical in shape. The FT-IR spectrum has a distinct absorption band at 2065 cm-1 confirms adsorption of antibiotic linezolid on the AgNPs. The XRD pattern showed the characteristic absorption bands of 2 theta values, which confirms that NPs are crystalline in nature. The AgNPs and Li-AgNPs have exhibited the antibacterial potency. The Li-AgNPs have showed 25.8%, 7.6%, and 12.5% more microbial growth inhibition compared to antibiotic linezolid against E. faecalis, E. faecium,and S. aureus,respectively. 

All these results clearly indicated that the Li-AgNPs possesses enhanced antimicrobial activity than antibiotic linezolid, indicating the usefulness of this novel strategy to treat various communicable diseases caused by MDR pathogens.