Nanoparticle-based Delivery Systems Research Articles

Preparation and characterization of BSA as a model protein loaded chitosan nanoparticles for the development of protein-/peptide-based drug delivery system

BackgroundThe purpose of this study was to develop protein-/peptide-loaded nanoparticle-based delivery system, which can efficiently deliver therapeutic molecules to the lung via pulmonary delivery. The chitosan nanoparticles were prepared by the ionic gelation method, and bovine serum albumin was used as a model protein. These nanoparticles were characterized for size, zeta potential, encapsulation efficiency, cell cytotoxicity, uptake study, release profile and size distribution and uniformity. The chemical interaction of chitosan and protein was studied by XRD and FTIR. The integrity assessment of encapsulated protein into nanoparticle was studied by native and SDS-PAGE gel electrophoresis.ResultsThe size and zeta potential of BSA nanoparticles were 193.53 ± 44.97 to 336.36 ± 94.63 and 12.73 ± 0.41 to 18.33 ± 0.96, respectively, with PDI values of 0.35–0.45. The encapsulation efficiency was in the range of 80.73 ± 6.37% to 92.34 ± 1.72%. The cumulative release of the BSA from the nanoparticles was 72.56 ± 6.67% in 2 weeks. The BSA-loaded nanoparticles showed good uptake and no significant cytotoxicity observed into the A549 cell line. In this study, it was also observed that during nanoparticles’ synthesis protein structure and integrity is not compromised. The nanoparticles showed controlled and sustained release with initial burst release. In TEM images, it was shown that nanoparticles’ distribution is uniform within nanometre range.ConclusionFrom this study, it was concluded that nanoparticles prepared by this method are suitable to deliver protein/peptide into the cells without any degradation of protein during process of nanoparticle fabrication.

Ethanol-soluble polysaccharide from sugar beet pulp for stabilizing zein nanoparticles and improving encapsulation of curcumin

Ethanol-soluble polysaccharide (ESP) is a highly ethanol-soluble (85% v/v) fraction from the precipitation process of sugar beet pectin and holds the potential to be utilized for food purposes. This study aimed to explore ESP as a coating polymer to stabilize zein nanoparticles against agglomeration via co-dissolving ESP and zein in an ethanol/water mixture (85% v/v) and subsequently dispersing into the water to form composite nanoparticles. Structural analyses showed that the ESP contained 28.3 wt% galacturonic acid, 45.7 wt% neutral sugar, and 17.6 wt% protein, and that its average molecular weight was 93,157 Da. In this study, we fabricated ESP-coated zein (zein-ESP) nanoparticles with a diameter of around 248 nm using the antisolvent co-precipitation method. These zein-ESP nanoparticles were stable over a wide pH range of 2.0–8.0 when the ESP:zein mass ratio was higher than 0.6:1. Additionally, the nanoparticles exhibited good stability in environmental stresses such as sodium ion concentrations of 400 mM and high temperatures of 90 °C (for 120 min). The encapsulation efficiency of Cur improved significantly, from 68.5% with the zein nanoparticles to 88.7% with the zein-ESP nanoparticles. When encapsulated by zein-ESP nanoparticles, Cur presented as an amorphous form and was released in a sustained and controlled manner after exposure to simulated gastrointestinal fluids, resulting in enhanced solubility and in vitro bioaccessibility, as compared with the free Cur. Altogether, ESP has great potential to stabilize zein nanoparticles-based delivery systems for hydrophobic bioactive compounds with enhanced water solubility and encapsulation efficiency for use in the food and pharmaceutical industries.

Design and Optimization of the Circulatory Cell-Driven Drug Delivery Platform.

Achievement of high targeting efficiency for a drug delivery system remains a challenge of tumor diagnoses and nonsurgery therapies. Although nanoparticle-based drug delivery systems have made great progress in extending circulation time, improving durability, and controlling drug release, the targeting efficiency remains low. And the development is limited to reducing side effects since overall survival rates are mostly unchanged. Therefore, great efforts have been made to explore cell-driven drug delivery systems in the tumor area. Cells, particularly those in the blood circulatory system, meet most of the demands that the nanoparticle-based delivery systems do not. These cells possess extended circulation times and innate chemomigration ability and can activate an immune response that exerts therapeutic effects. However, new challenges have emerged, such as payloads, cell function change, cargo leakage, and in situ release. Generally, employing cells from the blood circulatory system as cargo carriers has achieved great benefits and paved the way for tumor diagnosis and therapy. This review specifically covers (a) the properties of red blood cells, monocytes, macrophages, neutrophils, natural killer cells, T lymphocytes, and mesenchymal stem cells; (b) the loading strategies to balance cargo amounts and cell function balance; (c) the cascade strategies to improve cell-driven targeting delivery efficiency; and (d) the features and applications of cell membranes, artificial cells, and extracellular vesicles in cancer treatment.

Biocontrol Delivery System of <i>Trichoderma harzianum</i> Formulated in Graphite and Silica Nano Particles to Control <i>Rhizoctonia solani</i> on Tomato Plants

This paper reports the performance of a graphite and silica nanoparticles-based delivery system forT. harzianumin controlling the in vitro growth ofR. solaniand damping-off disease on tomato plants. The in vitro and in vivo experiments were arranged in the randomized complete block design. The in vitro treatment was a dual culture ofR. solaniandT. harzianumin the various components of formulation on PDA, i.e.,T. harzianum+ 5 wt.% graphite,T. harzianum+ 1wt.% silica NPs.,T. harzianum+ 5 wt.% graphite + 1 wt.% silica nanoparticles,T. harzianum, 5 wt.% graphite, 1 wt.% silica nanoparticles, fungicide (mancozeb), and a control. The in vivo treatment included the application ofT. harzianumin the same compositions as the in vitro treatment, except that there were two controls i.e., inoculated and noninoculated tomato plants withR. solani.T. harzianumby soaking tomato seeds in the formulation suspensions before planting. The results showed that all formulation compositions were able to inhibit the in vitro growth ofR. solani. The inhibitions of the colony growth ofR. solanicaused by formulated and non-formulatedT. harzianumwere the same. This proved that graphite and silica NPs did not resist to the ability ofT. harzianumin controllingR. solani, indicated that the formulation was promising to develop. However, the inhibition of damping-off disease incidence on tomato plants caused by formulatedT. harzianumwas the same as the non-formulated one only on day 7 after treatments. On days 14, 21, and 28, the inhibitions were lower than the non-formulated ones. It was suggested to reapply the formulation ofT. harzianumin the soil at planting and several days after.

Role of NKT Cells during Viral Infection and the Development of NKT Cell-Based Nanovaccines.

Natural killer T (NKT) cells, a small population of T cells, are capable of influencing a wide range of the immune cells, including T cells, B cells, dendritic cells and macrophages. In the present review, the antiviral role of the NKT cells and the strategies of viruses to evade the functioning of NKT cell have been illustrated. The nanoparticle-based formulations have superior immunoadjuvant potential by facilitating the efficient antigen processing and presentation that favorably elicits the antigen-specific immune response. Finally, the immunoadjuvant potential of the NKT cell ligand was explored in the development of antiviral vaccines. The use of an NKT cell-activating nanoparticle-based vaccine delivery system was supported in order to avoid the NKT cell anergy. The results from the animal and preclinical studies demonstrated that nanoparticle-incorporated NKT cell ligands may have potential implications as an immunoadjuvant in the formulation of an effective antiviral vaccine that is capable of eliciting the antigen-specific activation of the cell-mediated and humoral immune responses.

Nanobiotechnology and Immunotherapy: Two Powerful and Cooperative Allies against Cancer.

Simple SummaryConventional anti-cancer treatments for metastatic tumors include chemotherapy and radiation. These approaches can result in harmful side-effects and, in the vast majority of cases, are not curative. Recently, novel treatments have been developed in order to stimulate the host immune system to fight cancer. This type of therapeutic approach, called immunotherapy, has gained a lot of attention in recent years due to discoveries that have deciphered the immunosuppressive role of the tumor microenvironment and underpinning molecular signals. To enhance the delivery of therapeutic drugs to the tumor site, nanoparticle-based delivery systems can be used to reduce off-target effects, and to modulate immune cells present in the tumor microenvironment. This novel therapeutic approach can synergize with other immunotherapies such as immune checkpoint blockade inhibitors and adoptive cell therapy, by enhancing the infiltration of activated immune cells to the tumor site, and by limiting local immunosuppression.A number of novel cancer therapies have recently emerged that have rapidly moved from the bench to the clinic. Onco-immunotherapies, such as immune checkpoint blockade inhibitors and adoptive cell therapies, have revolutionized the field, since they provide a way to induce strong anti-tumor immune responses, which are able to fight cancer effectively. However, despite showing great efficacy in hematological and some solid tumors, unresponsiveness, development of therapy resistance and the development of serious adverse effects, limit their capacity to impact the vast majority of tumors. Nanoparticle-based delivery systems are versatile vehicles for a wide variety of molecular cargoes and provide an innovative strategy to improve conventional onco-immunotherapies. They can be finely tuned to release their contents in the tumor microenvironment, or to deliver combinations of adjuvants and antigens in the case of nanovaccines. In this review, we summarize the recent advancements in the field of nanobiotechnology, to remodel the tumor microenvironment and to enhance immunotherapies.

A non-invasive nanoparticle-based sustained dual-drug delivery system as an eyedrop for endophthalmitis

Endophthalmitis is an infectious disease that affects the entire eye spreading to the internal retinal layers and the vitreous and causes severe sight-threatening conditions. Current treatment strategies rely on intraocular injections of antibiotics that are invasive, may lead to procedural complications and, ultimately, blindness. In this study, we developed a non-invasive strategy as an eyedrop containing nanoparticle-based dual-drug delivery system in which the hydrophobic poly-L-lactide core was loaded with azithromycin or triamcinolone acetonide, and the hydrophilic shell was made of chitosan. The developed nanoparticles were ~200–250 nm in size, spherical in shape, moderately hydrophilic, lysozyme tolerant, cytocompatible, and hemocompatible. Application of these chitosan-coated nanoparticles as eye drops to C57BL/6 mice showed higher bioavailability in choroid and retina when compared to the uncoated nanoparticles. The delivery system showed sustained release of drug for 300 h and exhibited antimicrobial effects against Gram-positive and Gram-negative bacteria and anti-inflammatory effects on activated microglial cells. Interestingly, the combination of the nanoparticles loaded with azithromycin and the nanoparticles loaded with triamcinolone acetonide acted synergistically as compared to either of the nanoparticles/drugs alone. Overall, the developed dual-drug delivery system is non-invasive, has antimicrobial and anti-inflammatory effects, and shows potential as an eye drop formulation against endophthalmitis.

In Vitro Evaluation of a Nanoparticle-Based mRNA Delivery System for Cells in the Joint.

Biodegradable and bioresponsive polymer-based nanoparticles (NPs) can be used for oligonucleotide delivery, making them a promising candidate for mRNA-based therapeutics. In this study, we evaluated and optimized the efficiency of a cationic, hyperbranched poly(amidoamine)s-based nanoparticle system to deliver tdTomato mRNA to primary human bone marrow stromal cells (hBMSC), human synovial derived stem cells (hSDSC), bovine chondrocytes (bCH), and rat tendon derived stem/progenitor cells (rTDSPC). Transfection efficiencies varied among the cell types tested (bCH 28.4% ± 22.87, rTDSPC 18.13% ± 12.07, hBMSC 18.23% ± 14.80, hSDSC 26.63% ± 8.81) and while an increase of NPs with a constant amount of mRNA generally improved the transfection efficiency, an increase of the mRNA loading ratio (2:50, 4:50, or 6:50 w/w mRNA:NPs) had no impact. However, metabolic activity of bCHs and rTDSPCs was significantly reduced when using higher amounts of NPs, indicating a dose-dependent cytotoxic response. Finally, we demonstrate the feasibility of transfecting extracellular matrix-rich 3D cell culture constructs using the nanoparticle system, making it a promising transfection strategy for musculoskeletal tissues that exhibit a complex, dense extracellular matrix.

Metal-Organic Frameworks-Based Nanomaterials for Drug Delivery.

The composition and topology of metal-organic frameworks (MOFs) are exceptionally tailorable; moreover, they are extremely porous and represent an excellent Brunauer–Emmett–Teller (BET) surface area (≈3000–6000 m2·g−1). Nanoscale MOFs (NMOFs), as cargo nanocarriers, have increasingly attracted the attention of scientists and biotechnologists during the past decade, in parallel with the evolution in the use of porous nanomaterials in biomedicine. Compared to other nanoparticle-based delivery systems, such as porous nanosilica, nanomicelles, and dendrimer-encapsulated nanoparticles, NMOFs are more flexible, have a higher biodegradability potential, and can be more easily functionalized to meet the required level of host–guest interactions, while preserving a larger and fully adjustable pore window in most cases. Due to these unique properties, NMOFs have the potential to carry anticancer cargos. In contrast to almost all porous materials, MOFs can be synthesized in diverse morphologies, including spherical, ellipsoidal, cubic, hexagonal, and octahedral, which facilitates the acceptance of various drugs and genes.

Production and Characterization of Motile and Chemotactic Bacterial Minicells.

Minicells are nanosized membrane vesicles produced by bacteria. Minicells are chromosome-free but contain cellular biosynthetic and metabolic machinery, and they are robust due to the protection provided by the bacterial cell envelope, which makes them potentially highly attractive in biomedical applications. However, the applicability of minicells and other nanoparticle-based delivery systems is limited by their inefficient accumulation at the target. Here we engineered the minicell-producing Escherichia coli strain to overexpress flagellar genes, which enables the generation of motile minicells. We subsequently performed an experimental and theoretical analysis of the minicell motility and their responses to gradients of chemoeffectors. Despite important differences between the motility of minicells and normal bacterial cells, minicells were able to bias their movement in chemical gradients and to accumulate toward the sources of chemoattractants. Such motile and chemotactic minicells may thus be applicable for an active effector delivery and specific targeting of tissues and cells according to their metabolic profiles.

Cell-Specific Delivery Using an Engineered Protein Nanocage.

Nanoparticle-based delivery systems have shown great promise for theranostics and bioimaging on the laboratory scale due to favorable pharmacokinetics and biodistribution. In this study, we examine the utility of a cage-forming variant of the protein lumazine synthase, which was previously designed and evolved to encapsulate biomacromolecular cargo. Linking antibody-binding domains to the exterior of the cage enabled binding of targeting immunoglobulins and cell-specific uptake of encapsulated cargo. Protein nanocages displaying antibody-binding domains appear to be less immunogenic than their unmodified counterparts, but they also recruit serum antibodies that can mask the efficacy of the targeting antibody. Our study highlights the strengths and limitations of a common targeting strategy for practical nanoparticle-based delivery applications.

Cytoplasmic delivery of small interfering RNA by photoresponsive non-cationic liposomes

Small interfering RNA (siRNA) can specifically suppress gene expression by cleaving mRNA in the cytoplasm, termed RNA interference (RNAi). Although a nanoparticle-based siRNA delivery system has been approved for clinical use, the efficiency of cytoplasmic delivery of siRNA is still low. Recently, our group has established a highly efficient siRNA encapsulation method using non-cationic liposomes (LPs), which are more biocompatible than conventional cationic LPs. While non-cationic LPs containing siRNA were taken up by cells in vitro, the cytoplasmic release of siRNA and subsequent phenomena involving RNAi were not observed. It was considered that cytoplasmic delivery of siRNA, and siRNA release from LPs, should occur sequentially. We utilized amphiphilic photosensitizer Al (III) phthalocyanine chloride disulfonic acid (AlPcS2a), which can generate singlet oxygen under exposure to red light. When SK-HEP-1 cells expressing luciferase were treated with non-cationic LPs containing both siRNA and AlPcS2a, RNAi could be observed upon red light exposure, suggesting that singlet oxygen efficiently disrupts the membranous structures of endo/lysosomes and LPs. Thus, the combined use of AlPcS2a and red light is effective for utilizing non-cationic LPs for cytoplasmic delivery of siRNA.

A mussel-inspired film for adhesion to wet buccal tissue and efficient buccal drug delivery

Administration of drugs via the buccal route has attracted much attention in recent years. However, developing systems with satisfactory adhesion under wet conditions and adequate drug bioavailability still remains a challenge. Here, we propose a mussel-inspired mucoadhesive film. Ex vivo models show that this film can achieve strong adhesion to wet buccal tissues (up to 38.72 ± 10.94 kPa). We also demonstrate that the adhesion mechanism of this film relies on both physical association and covalent bonding between the film and mucus. Additionally, the film with incorporated polydopamine nanoparticles shows superior advantages for transport across the mucosal barrier, with improved drug bioavailability (~3.5-fold greater than observed with oral delivery) and therapeutic efficacy in oral mucositis models (~6.0-fold improvement in wound closure at day 5 compared with that observed with no treatment). We anticipate that this platform might aid the development of tissue adhesives and inspire the design of nanoparticle-based buccal delivery systems.

Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice.

Nanoparticle-based delivery systems for cancer immunotherapies aim to improve the safety and efficacy of these treatments through local delivery to specialized antigen-presenting cells (APCs). Multifunctional mesoporous silica nanoparticles (MSNs), with their large surface areas, their tunable particle and pore sizes, and their spatially controlled functionalization, represent a safe and versatile carrier system. In this study, we demonstrate the potential of MSNs as a pH-responsive drug carrier system for the anticancer immune-stimulant R848 (resiquimod), a synthetic Toll-like receptor 7 and 8 agonist. Equipped with a biotin-avidin cap, the tailor-made nanoparticles showed efficient stimuli-responsive release of their R848 cargo in an environmental pH of 5.5 or below. We showed that the MSNs loaded with R848 were rapidly taken up by APCs into the acidic environment of the lysosome and that they potently activated the immune cells. Upon subcutaneous injection into mice, the particles accumulated in migratory dendritic cells (DCs) in the draining lymph nodes, where they strongly enhanced the activation of the DCs. Furthermore, simultaneous delivery of the model antigen OVA and the adjuvant R848 by MSNs resulted in an augmented antigen-specific T-cell response. The MSNs significantly improved the pharmacokinetic profile of R848 in mice, as the half-life of the drug was increased 6-fold, and at the same time, the systemic exposure was reduced. In summary, we demonstrate that MSNs represent a promising tool for targeted delivery of the immune modulator R848 to APCs and hold considerable potential as a carrier for cancer vaccines.

Novel pH-responsive nanohybrid for simultaneous delivery of doxorubicin and paclitaxel: an in-silico insight

BackgroundThe distribution of drugs could not be controlled in the conventional delivery systems. This has led to the developing of a specific nanoparticle-based delivery system, called smart drug delivery systems. In cancer therapy, innovative biocompatible nanocarriers have received much attention for various ranges of anti-cancer drugs. In this work, the effect of an interesting and novel copolymer named "dimethyl acrylamide-trimethyl chitosan" was investigated on delivery of paclitaxel and doxorubicin applying carboxylated fullerene nanohybrid. The current study was run via molecular dynamics simulation and quantum calculations based on the acidic pH differences between cancerous microenvironment and normal tissues. Furthermore, hydrogen bonds, radius of gyration, and nanoparticle interaction energies were studied here. Stimulatingly, a simultaneous pH and temperature-responsive system were proposed for paclitaxel and doxorubicin for a co-polymer. A pH-responsive and thermal responsive copolymer were utilized based on trimethyl chitosan and dimethyl acrylamide, respectively. In such a dualistic approach, co-polymer makes an excellent system to possess two simultaneous properties in one bio-polymer.ResultsThe simulation results proposed dramatic and indisputable effects of the copolymer in the release of drugs in cancerous tissues, as well as increased biocompatibility and drug uptake in healthy tissues. Repeated simulations of a similar article performed for the validation test. The results are very close to those of the reference paper.ConclusionsOverall, conjugated modified fullerene and dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) as nanohybrid can be an appropriate proposition for drug loading, drug delivery, and drug release on dual responsive smart drug delivery system.

Nanoparticle-based inner ear delivery systems for the treatment of hearing loss

Hearing loss has become the most common sensory disorder worldwide. Despite intensive research on the pathophysiology of hearing loss, biological therapeutic approaches are limited by the anatomical and physiological characteristics of the inner ear. Challenges in inner ear drug delivery involve biotherapeutic instability, membrane inaccessibility and delivery non-specificity. With the development of nanotechnology, the nanoparticle-based delivery systems are promising to overcome these limitations. After drugs loading and stabilization, nanoparticles can carry the drugs into the inner ear by crossing round window membrane. The surface bioconjugation of ligand endows nanoparticles with specific targeting capability. Nanoparticles with stimuli-responsive moieties can provide a controlled release manner. Together, these strategies show great potential for hearing loss treatment. Understanding the current advances of nanotechnology in hearing loss treatment will facilitate future therapeutic options and clinical applications.

Nanoparticles Enable Efficient Delivery of Antimicrobial Peptides for the Treatment of Deep Infections

Abstract Antimicrobial peptides (AMPs) have emerged as promising alternatives of traditional antibiotics against drug-resistant bacteria owing to their broad-spectrum antimicrobial properties and low tendency to drug resistance. However, their therapeutic efficacy in vivo, especially for infections in deep organs, is limited owing to their systemic toxicity and low bioavailability. Nanoparticles-based delivery systems offer a strategy to increase the therapeutic index of AMPs by preventing proteolysis, increasing the accumulation at infection sites, and reducing toxicity. Herein, we will discuss the current progress of using nanoparticles as delivery vehicles for AMPs for the treatment of deep infections. Statement of significance Antimicrobial peptides (AMPs) are rarely directly used to treat deep infections due to their systemic toxicity and low bioavailability. This review summarizes recent progress that researchers employed nanoparticles-based delivery systems to deliver AMPs for the treatment of deep infections. Nanoparticles-based delivery systems offer a strategy to increase the therapeutic index of AMPs by preventing proteolysis, increasing the accumulation at infection sites, and reducing toxicity. Especially, the development of intelligent nanocarriers can achieve selective activation and active target in the infectious sites, thus improving the therapeutic efficacy against bacterial infection and reducing the toxicity against normal tissues.

Nanotherapeutics approaches to improve the efficacy of CAR-T cells in solid tumors

Adoptive cell therapy and Immune Checkpoint Blockade Inhibitors have recently revolutionized the field of oncology. However, these types of immunotherapeutic approaches have limited success in treating solid tumors. In particular, chimeric antigen receptor (CAR)-T cells efficacy is hampered by immunosuppressive signals in the tumor microenvironment (TME) and by a limited infiltration of re-infused T cells to the tumor site. The field of nanobiotechnology applied to oncology is also rapidly expanding. Nanoparticles-based delivery systems can be employed to modulate the activity of immune cells present in the TME enhancing the efficacy of CAR-T cells. Interestingly, nano-backpacks can be attached to CAR-T cells prior to re-infusion to support their homing to the tumor site and to slowly release immunopotentiators directly in the TME. Furthermore, nanovaccines can also be employed to support the in vivo expansion of CAR-T cells with consequent enhancement of their therapeutic potential. In this viewpoint, recent advancement in the field of nanobiotechnology to support CAR-T cell therapy will be discussed. The development of novel therapeutic CAR-T cells protocols together with nanotherapies is warranted in order to take full advantage of the high therapeutic potential of CAR-T cell therapy.

Research trends in pharmacological modulation of tumor-associated macrophages.

As one of the most abundant immune cell populations in the tumor microenvironment (TME), tumor‐associated macrophages (TAMs) play important roles in multiple solid malignancies, including breast cancer, prostate cancer, liver cancer, lung cancer, ovarian cancer, gastric cancer, pancreatic cancer, and colorectal cancer. TAMs could contribute to carcinogenesis, neoangiogenesis, immune‐suppressive TME remodeling, cancer chemoresistance, recurrence, and metastasis. Therefore, reprogramming of the immune‐suppressive TAMs by pharmacological approaches has attracted considerable research attention in recent years. In this review, the promising pharmaceutical targets, as well as the existing modulatory strategies of TAMs were summarized. The chemokine–chemokine receptor signaling, tyrosine kinase receptor signaling, metabolic signaling, and exosomal signaling have been highlighted in determining the biological functions of TAMs. Besides, both preclinical research and clinical trials have suggested the chemokine–chemokine receptor blockers, tyrosine kinase inhibitors, bisphosphonates, as well as the exosomal or nanoparticle‐based targeting delivery systems as the promising pharmacological approaches for TAMs deletion or reprogramming. Lastly, the combined therapies of TAMs‐targeting strategies with traditional treatments or immunotherapies as well as the exosome‐like nanovesicles for cancer therapy are prospected.

Home-made in vitro magnetic nanoparticle-based gene delivery system

Introduction: Biotechnology applications of Magnetic Nanoparticles (MNPs) have been rapidly investigated and are becoming the leading trend in the field. Although making an appearance almost 20 years ago, gene delivery using magnetic nanoparticles has not achieved much significant success. This study aims to establish promising and simple MNP-based protocol for gene delivery initially. Specifically, we aim to evaluate whether sodium chloride (NaCl) could enhance gene transfer with naked plasmid DNA without the need to combine liposomes or polymersomes. Methods: In this work, our "homemade" MNPs were mixed with plasmid DNA (phEF1-hKO – which expresses orange fluorescence) under various treatments of NaCl to enhance the formation of MNP-DNA complex for transfection. Then, these complexes were added to cultured cells. Delivery efficiency was represented by fluorescent expressing cells. Results: NaCl facilitated the magnetofection process in a dose and treatment duration co-dependent manner. Initial data showed that the optimal condition was 150mM NaCl with a 40-minute duration. Conclusion: Our homemade gene delivery system based on magnetic nanoparticles was established successfully. The viability of cells in magnetofection was maintained. Magnetofection without liposomes and polymersomes is certainly possible, but further researches have to be carried out in order to tell the definite optimal conditions.