Free Nanoparticles Research Articles

Thermo-Responsive Hydrogels Encapsulating Targeted Core-Shell Nanoparticles as Injectable Drug Delivery Systems.

As therapeutic agents that allow for minimally invasive administration, injectable biomaterials stand out as effective tools with tunable properties. Furthermore, hydrogels with responsive features present potential platforms for delivering therapeutics to desired sites in the body. Herein, temperature-responsive hydrogel scaffolds with embedded targeted nanoparticles were utilized to achieve controlled drug delivery via local drug administration. Poly(N-isopropylacrylamide) (pNIPAM) hydrogels, prepared with an ethylene-glycol-based cross-linker, demonstrated thermo-sensitive gelation ability upon injection into environments at body temperature. This hydrogel network was engineered to provide a slow and controlled drug release profile by being incorporated with curcumin-loaded nanoparticles bearing high encapsulation efficiency. A core (alginate)-shell (chitosan) nanoparticle design was preferred to ensure the stability of the drug molecules encapsulated in the core and to provide slower drug release. Nanoparticle-embedded hydrogels were shown to release curcumin at least four times slower compared to the free nanoparticle itself and to possess high water uptake capacity and more mechanically stable viscoelastic behavior. Moreover, this therapy has the potential to specifically address tumor tissues over-expressing folate receptors like ovaries, as the nanoparticles target the receptors by folic acid conjugation to the periphery. Together with its temperature-driven injectability, it can be concluded that this hydrogel scaffold with drug-loaded and embedded folate-targeting nanoparticles would provide effective therapy for tumor tissues accessible via minimally invasive routes and be beneficial for post-operative drug administration after tumor resection.

Autophagy-targeted nanoparticles in breast carcinoma: A systematic review.

Breast cancer is a commonly known cancer type and the leading cause of cancer death among females. One of the unresolved problems in cancer treatment is the increased resistance of the tumor to existing treatments, which is a direct result of apoptotic defects. Calculating an alternative to cell death (autophagy) may be the ultimate solution to maximizing cancer cell death. Our aim in this study was to investigate the potential of free nanoparticles (un-drug-loaded) in the induction or inhibition of autophagy and consider this effect on the therapy process. When the studies met the inclusion criteria, the full texts of all relevant articles were carefully examined and classified. Of the 25 articles included in the analysis, carried out on MCF-7, MDA-MB-231, MDA-MB-231-TXSA, MDA-MB-468, SUM1315, and 4T1 cell lines. Twenty in vitro studies and fivein vivo/in vitro studies applied five different autophagy tests: Acridine orange, western blot, Cyto-ID Autophagy Detection Kit, confocal microscope, and quantitativepolymerase chain reaction. Nanoparticles(NPs) in the basic format, including Ag, Au, Y2 O3 , Se, ZnO, CuO, Al, Fe, vanadium pentoxide, and liposomes, were prepared in the included articles. Three behaviors of NPs related to autophagy were seen: induction, inhibition, and no action. Screened and presented data suggest that most of the involved free NPs (metallic NPs) in this systematic review had reactiveoxygenspecies-mediated pathways with autophagy induction (36%). Also, PI3K/Akt/mTOR and MAPK/ERK signaling pathways were mentioned in just four studies (16%). An impressive percentage of studies (31%) did not examine the NP-related autophagy pathway.

Fabricating niosomal-PEG nanoparticles co-loaded with metformin and silibinin for effective treatment of human lung cancer cells.

Despite current therapies, lung cancer remains a global issue and requires the creation of novel treatment methods. Recent research has shown that biguanides such as metformin (MET) and silibinin (SIL) have a potential anticancer effect. As a consequence, the effectiveness of MET and SIL in combination against lung cancer cells was investigated in this study to develop an effective and novel treatment method. Niosomal nanoparticles were synthesized via the thin-film hydration method, and field emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FTIR), atomic force microscopy (AFM), and dynamic light scattering (DLS) techniques were used to evaluate their physico-chemical characteristics. The cytotoxic effects of free and drug-loaded nanoparticles (NPs), as well as their combination, on A549 cells were assessed using the MTT assay. An apoptosis test was used while under the influence of medication to identify the molecular mechanisms behind programmed cell death. With the use of a cell cycle test, it was determined whether pharmaceutical effects caused the cell cycle to stop progressing. Additionally, the qRT-PCR technique was used to evaluate the levels of hTERT, BAX, and BCL-2 gene expression after 48-h medication treatment. In the cytotoxicity assay, the growth of A549 lung cancer cells was inhibited by both MET and SIL. Compared to the individual therapies, the combination of MET and SIL dramatically and synergistically decreased the IC50 values of MET and SIL in lung cancer cells. Furthermore, the combination of MET and SIL produced lower IC50 values and a better anti-proliferative effect on A549 lung cancer cells. Real-time PCR results showed that the expression levels of hTERT and BCL-2 were significantly reduced in lung cancer cell lines treated with MET and SIL compared to single treatments (p< 0.001). It is anticipated that the use of nano-niosomal-formed MET and SIL would improve lung cancer treatment outcomes and improve the therapeutic efficiency of lung cancer cells.

Effect of precursors on ZnO nanoparticles to enhance the level-III ridge details of LFPs and anti-counterfeiting applications

Comparative analysis for the combustion-based synthesis of zinc oxide nanoparticles (NPs) utilizing various precursors of zinc was reported. l-ascorbic acid extraction was used as a fuel for the combustion process. The sizes, morphologies, structural details and purity of samples were examined using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffractometry (XRD). XRD pattern matches with the standard JCPDS card of ZnO with good crystallite size. The average crystallite size of the NPs was confirmed the nano-regime. Variations in morphological structures and the energy band gap variation with the change in precursors was reported. Using a powder-dusting technique, on separate surfaces, level-III features of the fingerprints produced by these NPs without any background noise. The suggested powder composition was easy to make and effective for producing latent finger prints on a variety of dry and wet surfaces. In the area of counterfeit prevention, the fluorescent ink has several potential applications. Invisible security ink was developed for anti-counterfeiting applications based on the UV fluorescence feature of ZnO NPs. The fluorescent invisible security ink for screen printing was evaluated and proved to be stable on a variety of microporous papers. The new strategy adopted here lowers the cost of ink by using rare earth free ZnO NPs.

Anti-cancer effect of nano-encapsulated boswellic acids, curcumin and naringenin against HepG-2 cell line

Backgroundliver cancer is one of the most common cancers in the world. So far, there is no gold standard treatment for hepatocellular carcinoma. We conducted this in vitro study to assess the effect of three natural products: Boswellic acids, curcumin and naringin versus corresponding nanoparticles (NPs) on Hep G2 cells proliferation.MethodsBoswellic acid, curcumin, naringin-loaded NPs were prepared using nanoprecipitation method. Human liver (HepG2) cell line was cultured in Dulbecco’s modified Eagle’s medium (DMEM). The cell growth inhibition and cytotoxicity were evaluated by MTT assay.ResultsBoswellic acid, curcumin, naringin were able to inhibit HepG2 cells proliferation. IC50 at 24 h, 48 h showed significant lower values in NPs versus Free herbs. IC50 values of free Boswellic acids and NPs at 24 h were (24.60 ± 1.89 and 7.78 ± 0.54, P < 0.001), at 48 h were (22.45 ± 1.13 and 5.58 ± 0.27, P < 0.001) respectively. IC50 values of free curcumin and NPs at 24 h were (5.89 ± 0.8 and 3.46 ± 0.23, P < 0.05), at 48 h were (5.57 ± 0.94 and 2.51 ± 0.11, P < 0.05), respectively. For free and naringenin NPs, IC50 values at 24 h were (14.57 ± 1.78 and 7.25 ± 0.17, P < 0.01), at 48 h were (11.37 ± 1.45 and 5.21 ± 0.18, P < 0.01) respectively.ConclusionBoswellic acid, curcumin, naringin and their nanoprecipitation prepared nanoparticles suppressed Hep G2 cells proliferation.

Highly bright stable organic radicals encapsulated by amphiphilic polypeptide for efficient near-infrared phototheranostics

Stable organic radical molecules have received extensive attention due to their unique electronic structure and photophysical properties, and the highly fluorescent quantum efficiency has great appeal to bioimaging. However, still scarce reports on the application of them on the therapy of tumors, especially theranostics. Here, 3,6-dibromocarbazole modified tris (2,4,6-trichlorophenyl) methane radical (TB) has been synthesized with high NIR fluorescence quantum efficiency, and free radical nanoparticles (NPs) have been prepared using the precursor of the radical doping strategy. The free radical molecule TB and its precursor molecule HTB were mixed in proportion and encapsulated with an amphiphilic polypeptide (PEG-PAsp) to obtain the NPs. The 4% NPs can achieve a high fluorescence quantum efficiency (18.68%) in the NIR region. In addition, the NPs also have a good ability to produce reactive oxygen species (ROS) under either normoxia or hypoxia conditions, which makes it possible for photodynamic therapy (PDT). Interestingly, the NPs also show preferable photothermal ability (PCE = 42.39%) for photothermal therapy (PTT). Both in vitro and in vivo studies reveal that the as-prepared radical NPS show a NIR fluorescence imaging-guided synergistic PTT and type I/II PDT to tumors. It provides new strategies and new clues for the application of free radical molecules in the theranostics of tumors.

Intracellular Localization during Blood–Brain Barrier Crossing Influences Extracellular Release and Uptake of Fluorescent Nanoprobes

To improve the efficacy of nanoparticles (NPs) and boost their theragnostic potential for brain diseases, it is key to understand the mechanisms controlling blood–brain barrier (BBB) crossing. Here, the capability of 100 nm carboxylated polystyrene NPs, used as a nanoprobe model, to cross the human brain endothelial hCMEC/D3 cell layer, as well as to be consequently internalized by human brain tumor U87 cells, is investigated as a function of NPs’ different intracellular localization. We compared NPs confined in the endo-lysosomal compartment, delivered to the cells through endocytosis, with free NPs in the cytoplasm, delivered by the gene gun method. The results indicate that the intracellular behavior of NPs changed as a function of their entrance mechanism. Moreover, by bypassing endo-lysosomal accumulation, free NPs were released from cells more efficiently than endocytosed NPs. Most importantly, once excreted by the endothelial cells, free NPs were released in the cell culture medium as aggregates smaller than endocytosed NPs and, consequently, they entered the human glioblastoma U87 cells more efficiently. These findings prove that intracellular localization influences NPs’ long-term fate, improving their cellular release and consequent cellular uptake once in the brain parenchyma. This study represents a step forward in designing nanomaterials that are able to reach the brain effectively.

Designing Alginate/Chitosan Nanoparticles Containing Echinacea angustifolia: A Novel Candidate For Combating Multidrug-resistant Staphylococcus aureus.

Nanoparticles (NPs) may help treat multidrug-resistant Staphylococcus aureus (MDR). This study prepared and evaluated chitosan/alginate-encapsulated Echinacea angustifolia extract against MDR strains. Evaluating synthesized NPs with SEM, DLS, and FTIR. Congo red agar and colorimetric plate techniques examined isolate biofilm formation. NP antibacterial power was assessed using well diffusion. Real-time PCR assessed biofilm-forming genes. MTT assessed the synthesized NPs' toxicity. According to DLS measurements, spherical E. angustifolia NPs had a diameter of 335.3 ± 1.43 nm. The PDI was 0.681, and the entrapment effectiveness (EE%) of the E. angustifolia extract reached 83.45 %. Synthesized NPs were most antimicrobial. S. aureus resistant to several treatments was 80 percent of 100 clinical samples. Biofilm production was linked to MDR in all strains. The ALG/CS-encapsulated extract had a 4 to 32-fold lower MIC than the free extract, which had no bactericidal action. They also significantly decreased the expression of genes involved in biofilm formation. E. angustifolia-encapsulated ALG/CS decreased IcaD, IcaA, and IcaC gene expression in all MDR strains (***p<0.001). Free extract, free NPs, and E. angustifolia-NPs had 57.5%, 85.5%, and 90.0% cell viability at 256 μg/ml. These discoveries could assist generate stable plant extracts by releasing natural-derived substances under controlled conditions.

Preparation of Nanoparticle-Loaded Extracellular Vesicles Using Direct Flow Filtration.

Extracellular vesicles (EVs) have shown great potential as cell-free therapeutics and biomimetic nanocarriers for drug delivery. However, the potential of EVs is limited by scalable, reproducible production and in vivo tracking after delivery. Here, we report the preparation of quercetin-iron complex nanoparticle-loaded EVs derived from a breast cancer cell line, MDA-MB-231br, using direct flow filtration. The morphology and size of the nanoparticle-loaded EVs were characterized using transmission electron microscopy and dynamic light scattering. The SDS-PAGE gel electrophoresis of those EVs showed several protein bands in the range of 20-100 kDa. The analysis of EV protein markers by a semi-quantitative antibody array confirmed the presence of several typical EV markers, such as ALIX, TSG101, CD63, and CD81. Our EV yield quantification suggested a significant yield increase in direct flow filtration compared with ultracentrifugation. Subsequently, we compared the cellular uptake behaviors of nanoparticle-loaded EVs with free nanoparticles using MDA-MB-231br cell line. Iron staining studies indicated that free nanoparticles were taken up by cells via endocytosis and localized at a certain area within the cells while uniform iron staining across cells was observed for cells treated with nanoparticle-loaded EVs. Our studies demonstrate the feasibility of using direct flow filtration for the production of nanoparticle-loaded EVs from cancer cells. The cellular uptake studies suggested the possibility of deeper penetration of the nanocarriers because the cancer cells readily took up the quercetin-iron complex nanoparticles, and then released nanoparticle-loaded EVs, which can be further delivered to regional cells.

Study on free and entangled binary metal nanocatalysts for removal of 2,4,6-trichlorophenol in aqueous phase: a comparative study

The present study highlights the comparative catalytic removal of 2,4,6-trichlorophenol (TCP) in the aqueous phase by binary nanoparticles in free as well as entangled forms. In brief, binary nanoparticles comprising Fe–Ni are prepared, characterized, and subsequently entangled in reduced graphene oxide (rGO) for better performances. Optimization studies on the mass of free and rGO-entangled binary nanoparticles with respect to TCP concentration and other environmental factors were carried out. Results suggested that free binary nanoparticles at 40 mg ml−1 took 300 min to dechlorinate 600 ppm of TCP, whereas rGO-entangled Fe–Ni particles at the same mass took only 190 min to dechlorinate when the pH was maintained at near neutral. In addition, experiments on the reuse of the catalyst with respect to removal efficiency were carried out, and the results implied that, compared to free form, rGO-entangled nanoparticles exemplify more than 98% of removal efficacy even after 5 times of exposure to 600 ppm TCP concentration. The reduction in percentage removal was observed after the sixth exposure. A sequential dechlorination pattern was assessed and confirmed using high-performance liquid chromatography. Further, the phenol-enriched aqueous phase is exposed to Bacillus licheniformis SL10, which degrades the phenol effectively within 24 h. In conclusion, the prepared binary nanoparticles, both in free as well as in rGO-entangled forms, effectively dechlorinate 2,4,6-TCP contaminations in the aqueous phase, but with differences in removal duration. Entanglement also makes it easier to reuse the catalyst. Furthermore, microbial phenol degradation allows the aqueous phase to be free of 2, 4, and 6-TCP contamination and allows for the reuse of treated water.

Integrated multi-omics analysis reveals unique signatures of paclitaxel-loaded poly(lactide-co-glycolide) nanoparticles treatment of head and neck cancer cells.

The use of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) as carriers for chemotherapeutic drugs is regarded as an actively targeted nano-therapy for the specific delivery of anti-cancer drugs to target cells. However, the exact mechanism by which PLGA NPs boost anticancer cytotoxicity at the molecular level remains largely unclear. This study employed different molecular approaches to define the response of carcinoma FaDu cells to different types of treatment, specifically: paclitaxel (PTX) alone, drug free PLGA NPs, and PTX-loaded PTX-PLGA NPs. Functional cell assays revealed that PTX-PLGA NPs treated cells had a higher level of apoptosis than PTX alone, whereas the complementary, UHPLC-MS/MS (TIMS-TOF) based multi-omics analyses revealed that PTX-PLGA NPs treatment resulted in increased abundance of proteins associated with tubulin, as well as metabolites such as 5-thymidylic acid, PC(18:1(9Z)/18:1(9Z0), vitamin D, and sphinganine among others. The multi-omics analyses revealed new insights about the molecular mechanisms underlying the action of novel anticancer NP therapies. In particular, PTX-loaded NPs appeared to exacerbate specific changes induced by both PLGA-NPs and PTX as a free drug. Hence, the PTX-PLGA NPs' molecular mode of action, seen in greater detail, depends on this synergy that ultimately accelerates the apoptotic process, resulting in cancer cell death.

Comparison of antibacterial activity and cytotoxicity of silver nanoparticles and silver-loaded montmorillonite and saponite

Although silver nanoparticles are known for their antibacterial activity, little research has been carried out on what synthesis method provides the most effective particles. In this study, silver nanoparticles were synthesised via chemical reduction by using silver nitrate as the silver precursor, ascorbic acid as the reducing agent and sodium citrate as the stabilising agent. The solutions were adjusted to several pH values employing sodium hydroxide, citric acid or nitric acid. Dynamic light scattering and absorption spectra in the ultraviolet/visible region characterisation revealed that employing nitric acid to adjust the pH produced more varied and larger silver particle sizes. Then, silver nanoparticles were supported on montmorillonite and saponite through wet impregnation or ion exchange methods. Scanning electron microscopy, energy-dispersive X-ray spectroscopy and transmission electron microscopy characterisation confirmed that silver nanoparticles were successfully loaded onto the clay minerals. Next, the antibacterial activity of the samples was evaluated against Escherichia coli and Staphylococcus aureus by determining their minimum inhibitory concentrations and minimum bactericidal concentrations. The free silver nanoparticles did not show any antibacterial activity at 125 mg/L. In contrast, the silver-loaded samples obtained by wet impregnation and with a higher silver content displayed the strongest antibacterial effect. Finally, the cytotoxicity of the samples was determined in GM07492-A cell line by using an XTT colorimetric assay. The calculated IC50 values revealed that the supported silver nanoparticles were barely toxic. Thus, the silver-loaded clay minerals obtained here are promising antibacterial materials with a high-grade safety profile.

CNP-miR146a improves outcomes in a two-hit acute- and ventilator-induced lung injury model

Acute respiratory distress syndrome (ARDS) has high mortality (~40 %) and requires the lifesaving intervention of mechanical ventilation. A variety of systemic inflammatory insults can progress to ARDS, and the inflamed and injured lung is susceptible to ventilator-induced lung injury (VILI). Strategies to mitigate the inflammatory response while restoring pulmonary function are limited, thus we sought to determine if treatment with CNP-miR146a, a conjugate of novel free radical scavenging cerium oxide nanoparticles (CNP) to the anti-inflammatory microRNA (miR)-146a, would protect murine lungs from acute lung injury (ALI) induced with intratracheal endotoxin and subsequent VILI. Lung injury severity and treatment efficacy were evaluated via lung mechanical function, relative gene expression of inflammatory biomarkers, and lung morphometry (stereology). CNP-miR146a reduced the severity of ALI and slowed the progression of VILI, evidenced by improvements in inflammatory biomarkers, atelectasis, gas volumes in the parenchymal airspaces, and the stiffness of the pulmonary system.

Development and characterization of lung surfactant-coated polymer nanoparticles for pulmonary drug delivery

Lung cancer is often diagnosed at an advanced stage where tumors are usually inoperable and first-line therapies are inefficient and have off-targeted adverse effects, resulting in poor patient survival. Here, we report the development of an inhalable poly lactic-co-glycolic acid polymer-based nanoparticle (PLGA-NP) formulation with a biomimetic Infasurf® lung surfactant (LS) coating, for localized and sustained lung cancer drug delivery. The nanoparticles (188 ± 7 nm) were stable in phosphate buffered saline, serum and Gamble's solution (simulated lung fluid), and demonstrated cytocompatibility up to 1000 μg/mL concentration and dose-dependent uptake by lung cancer cells. The LS coating significantly decreased nanoparticle (NP) uptake by NR8383 alveolar macrophages in vitro compared to uncoated NPs. The coating, however, did not impair NP uptake by A549 lung adenocarcinoma cells. The anti-cancer drug gemcitabine hydrochloride encapsulated in the PLGA core was released in a sustained manner while the paclitaxel loaded in the LS shell demonstrated a rapid or burst release profile over 21 days. The drug-loaded NPs significantly decreased cancer cell survival and colony formation in vitro compared to free drugs and single drug-loaded NPs. In vivo studies confirmed greater retention of LS-coated NPs in the lungs of C57BL/6 WT mice compared to uncoated NPs, at 24 h and 72 h following intranasal administration. The overall results confirm that LS coating is a unique strategy for cloaking polymeric NPs to potentially prevent their rapid lung clearance and facilitate prolonged pulmonary drug delivery.

Neutrophil hitchhiking for drug delivery to the bone marrow.

Pharmaceuticals have been developed for the treatment of a wide range of bone diseases and disorders, but suffer from problematic delivery to the bone marrow. Neutrophils are naturally trafficked to the bone marrow and can cross the bone marrow-blood barrier. Here we report the use of neutrophils for the targeted delivery of free drugs and drug nanoparticles to the bone marrow. We demonstrate how drug-loaded poly(lactic-co-glycolic acid) nanoparticles are taken up by neutrophils and are then transported across the bone marrow-blood barrier to boost drug concentrations in the bone marrow. We demonstrate application of this principle to two models. In a bone metastasis cancer model, neutrophil delivery is shown to deliver cabazitaxel and significantly inhibit tumour growth. In an induced osteoporosis model, neutrophil delivery of teriparatide is shown to significantly increase bone mineral density and alleviate osteoporosis indicators.

Targeting glutamine metabolism with photodynamic immunotherapy for metastatic tumor eradication

Immune checkpoint blockade (ICB) has shown significant clinical success, yet its responses can vary due to immunosuppressive tumor microenvironments. To enhance antitumor immunity, combining ICB therapy with tumor metabolism reprogramming may be a promising strategy. In this study, we developed a photodynamic immunostimulant called BVC aiming to boost immune recognition and prevent immune escape for metastatic tumor eradication by reprogramming glutamine metabolism. BVC, a carrier free self-assembled nanoparticle, comprises a photosensitizer (chlorin e6), an ASCT2 inhibitor (V9302) and a PD1/PDL1 blocker (BMS-1), offering favorable stability and enhanced drug delivery efficiency. The potent photodynamic therapy (PDT) capability of BVC is attributed to its regulation of glutamine metabolism, which influences the redox microenvironment within tumor tissues. By targeting ASCT2-mediated glutamine metabolism, BVC inhibits glutamine transport and GSH synthesis, leading to the upregulation of Fas and PDL1. Additionally, BVC-mediated PDT induces immunogenic cell death, triggering a cascade of immune responses. Consequently, BVC not only enhances immune recognition between CD8+ T cells and Fas-overexpressing tumor cells but also reduces tumor cell immune escape through PD1/PDL1 blockade, significantly benefiting metastatic tumor eradication. This study paves a novel approach for multi-synergistic tumor treatment.

Ag-oxide signature in Ag 3d photoelectron spectra: A study on free nanoparticles

Over decades the Ag 3d-level binding energy has been puzzling researchers with its unusual sign and value in silver oxides. For the absolute majority of metals, the metal-to-oxide binding energy shifts are positive and depend significantly on the oxidation state, while in Ag-oxides the oxide shift was time after time reported negative, small, and close for the two very different Ag(I) and Ag(III) oxidation states. In the current work, a photoelectron spectroscopy (PES) investigation on the in-situ created free nanoparticles simultaneously containing both metallic silver and silver-oxide parts provided the grounds to reconsider the old consensus on the Ag-oxide shifts. The Ag 3d energies for the metallic and the oxide parts established in the current experimental work allowed estimating a ≈ 1.2 eV positive shift for the realized oxidation state. This estimate was made possible by using a beam of free nanoparticles with finely controlled composition. The PES experiments on such a beam allowed for a continuous and fast renewal of the poorly conducting sample and for a reliable and accurate calibration relative to vacuum. The constant oxide shift observed at several different oxidation conditions, as well as the relatively narrow and symmetric oxide peaks, point to one dominating oxidation state being present in the particles.

Pegylated Gold Nanoparticles Conjugated with siRNA: Complexes Formation and Cytotoxicity

Drug delivery systems such as dendrimers, liposomes, polymers or gold/silver nanoparticles could be used to advance modern medicine. One significant pharmacological problem is crossing biological barriers by commonly used drugs, e.g., in the treatment of neurodegenerative diseases, which have a problem of the blood-brain barrier (BBB) restricting drug delivery. Numerous studies have been conducted to find appropriate drug carriers that are safe, biocompatible and efficient. In this work, we evaluate pegylated gold nanoparticles AuNP14a and AuNP14b after their conjugation with therapeutic siRNA directed against APOE4. This genetic risk factor remains the strongest predictor for late-onset Alzheimer's disease. The study aimed to assess the biophysical properties of AuNPs/siAPOE complexes and to check their biological safety on healthy cells using human brain endothelial cells (HBEC-5i). Techniques such as fluorescence polarization, circular dichroism, dynamic light scattering, ζ-potential measurements and gel retardation assay showed that AuNPs form stable complexes with siRNA. Subsequently, cytotoxicity assays proved the biological safety of formed conjugates. Obtained results enabled us to find effective concentrations of AuNPs when complexes are formed and non-toxic for healthy cells. One of the studied nanoparticles, AuNP14b complexed with siRNA, displayed lower cytotoxicity (MTT assay, cells viability -74.8 ± 3.1%) than free nanoparticles (44.7 ± 3.6%). This may be promising for further investigations in nucleic acid delivery and could have practical use in treating neurodegenerative diseases.

In vitro and in vivo study on the anticancer effects of anethole-loaded bovine serum albumin nanoparticles surface decorated with chitosan and folic acid

Anethole (Ant) is a herbal compound with unique properties, which is limited in its clinical use due to its low solubility in aqueous solutions. Therefore, in this study, albumin nanocarrier modified with chitosan-folate was used to transfer Ant to cancer cells and its anticancer effects were evaluated. First, Ant was loaded on albumin nanoparticles by desolvation method and then the surface of nanoparticles was covered with chitosan bound to folate. After characterization, the amount of Ant loading in nanoparticles was measured by the absorption method and then its toxicity effects on breast cancer cell lines, colon, and normal cells were evaluated by the MTT method. The real-time QPCR method was used to investigate the expression changes of apoptosis-related genes in the treated cells compared to the control cells, and finally, the antitumor effects of nanoparticles were evaluated in the mouse model carrying breast cancer. The results of this investigation showed the presence of nanoparticles with dimensions of 252 nm, a dispersion index of 0.28 mV, and a surface charge of 27.14 mV, which are trapped in about 88% of ATL. The toxicity effect of nanoparticles was shown on breast, colon, and normal cancer cells, respectively. In addition, the examination of the gene profile under investigation showed an increase in the expression of BAX and caspase-3 and -9 along with a decrease in the expression of the Bcl-2 gene, which confirms the activation of the internal pathway of apoptosis. The decrease in the volume of tumors and the presence of apoptotic areas in the tissue sections confirmed the antitumor effects of nanoparticles in the in vivo model. The inhibition percentage of free Ant and nanoparticles with a concentration of 25 and 50 mg/kg/tumor volume was reported as 36.9%, 56.6%, and 64.9%, respectively, during 15 days of treatment. These results showed the effectiveness of the formulation in inhibiting cancer cells both in vitro and in vivo.

Co-delivery of microRNA-150 and quercetin by lipid nanoparticles (LNPs) for the targeted treatment of age-related macular degeneration (AMD).

Age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV), which leads to severe vision loss in middle-aged and elderly patients. Current treatments for CNV show weak, transient efficacy, and they can cause several adverse effects. A potential new treatment is to use microRNA-150 (mR150), which regulates physiological and pathological angiogenesis by modulating the expression of CXCR4 at the post-transcriptional level. Here, we developed solid lipid nanoparticles that we modified with an Asp-Gly-Arg peptide to target endothelial cells during abnormal angiogenesis, then we co-loaded them with mR150 and the anti-angiogenic drug quercetin. The resulting nanoparticles had an average size around 200nm and showed strong ability to target the fundus and inhibit CNV for up to two weeks in a mouse model without causing retinal toxicity. They significantly enhanced the uptake of mR150 in vitro compared to free mR150 or nanoparticles without peptide. Our study suggests that co-administration of mR150 and quercetin has potential for treating age-related macular degeneration and that nanoparticles modified with Asp-Gly-Arg peptide are an effective platform for the co-delivery of small-molecule and nucleic acid drugs via intravitreal injection.