Acriflavine-loaded solid lipid nanoparticles: preparation, physicochemical characterization, and anti-proliferative properties.

Acriflavine (ACF) is an antiseptic compound with the potential antitumor activity which is used for the fluorescent staining of RNA due to its dominant fluorescent emission at ∼515 nm. Here, solid lipid nanoparticles (SLNs) containing ACF (ACF-SLNs) were prepared and their physicochemical properties, potential geno/cytotoxicity, as well as the fluorescent properties were investigated. FITC-annexin V/PI staining and cell cycle assays were carried out to find the type of cellular death caused. Particle size analysis and SEM images revealed that spherical ACF-SLNs had a homogeneous dispersion with a mean diameter of 106 ± 5.7 nm. Drug loading (DL) of 31.25 ± 4.21 mg/mL and high encapsulation efficiency (EE%) (89.75 ± 5.44) were found. ACF-SLNs physically were relatively stable in terms of dispersion, size, and EE. The uptake study demonstrated the potential use of fluorescent ACF-SLNs in bio-distribution studies. MTT assay showed that plain ACF could induce growth inhibition of A549 cells with IC50 of 8.5, 6, and 4.5 µMol after 24, 48, and 72 hours, respectively, while ACF-SLNs had stable cytotoxic effects after 48 hours. ACF-SLNs induced remarkable apoptosis and even necrosis after 48 h. Conclusively, ACF-SLNs with acceptable physicochemical features showed increased bioimpacts after 48 h compared to plain ACF.

A comprehensive review on nanocomposite biomaterials based on gelatin for bone tissue engineering.

The creation of a suitable scaffold is a crucial step in the process of bone tissue engineering (BTE). The scaffold, acting as an artificial extracellular matrix, plays a significant role in determining the fate of cells by affecting their proliferation and differentiation in BTE. Therefore, careful consideration should be given to the fabrication approach and materials used for scaffold preparation. Natural polypeptides such as gelatin and collagen have been widely used for this purpose. The unique properties of nanoparticles, which vary depending on their size, charge, and physicochemical properties, have demonstrated potential in solving various challenges encountered in BTE. Therefore, nanocomposite biomaterials consisting of polymers and nanoparticles have been extensively used for BTE. Gelatin has also been utilized in combination with other nanomaterials to apply for this purpose. Composites of gelatin with various types of nanoparticles are particularly promising for creating scaffolds with superior biological and physicochemical properties. This review explores the use of nanocomposite biomaterials based on gelatin and various types of nanoparticles together for applications in bone tissue engineering.

Protective effect of l-carnitine-loaded solid lipid nanoparticles against H2O2-induced genotoxicity and apoptosis.

L-carnitine (LC) is a highly water-soluble compound involved in the ß-oxidation of lipids and transportation of long-chain fatty acids across the membrane of mitochondria. However, the higher hydrophilicity of LC limits its free diffusion across the bilayer lipid membrane of intestinal epithelium in oral administration, decreasing oral bioavailability. Drug delivery with nanoparticles enhances cargo bioavailability and cellular uptake and improves therapeutic outcomes while decreasing unwanted side effects. Here, we proposed solid lipid nanoparticles (SLNs) as a hydrophobic carrier for LC delivery, aiming at increasing LC bioavailability and its protective role against intracellular oxidative stress damages. The LC-SLNs were prepared using the hot homogenization technique, and different physicochemical properties were investigated. The inhibition of H2O2-induced ROS generation in human umbilical vein endothelial cells (HUVECs) with plain LC and LC-SLNs was investigated. Moreover, various in vitro experiments were performed to assess whether LC-SLNs can protect HUVECs from H2O2-induced genotoxicity and apoptosis. The monodispersed and spherical blank SLNs and LC-SLNs were 104 ± 1.8 and 128 ± 1.5 nm, respectively with a drug loading (DL) of 11.49 ± 0.78 mg/mL and acceptable encapsulation efficiency (EE%) (69.09 ± 1.12) of LC-SLNs. The formulation process did not affect the antioxidant properties of LC. MTT assay and comet assay demonstrated that the LC-SLNs decreased cytotoxicity and genotoxicity of H2O2, respectively on HUVECs. Besides, LC-SLNs more inhibited ROS generation, along with apoptotic events in H2O2-treated HUVECs compared to the plain LC. Altogether, our findings affirmed the protective effects of LC-SLNs against H2O2-induced genotoxicity and apoptosis in HUVECs. In conclusion, LC-SLN formulation is a promising drug delivery system to overcome the bioavailability issue of hydrophilic LC, enhancing the antioxidant and biological properties of the plain LC.

Preparation, physicochemical characterization, and anti-proliferative properties of Lawsone-loaded solid lipid nanoparticles.

Lawsone (LWS) is a naphthoquinone-type dye with potential antitumor activity. LWS is used in cosmetics for coloring hair, skin, and nails. In this study, solid lipid nanoparticles (SLNs) containing LWS were prepared using a hot homogenization technique. Physicochemical properties of LWS-SLNs including encapsulation efficiency (EE), drug loading (DL), size, zeta potential, homogeneity, in vitro release, and kinetics of release were determined. The potential cytotoxic properties of LWS-SLNs were investigated. Comet assay was done to assess the genotoxicity of LWS-SLNs. The scanning electron microscopy (SEM) images revealed that LWS-SLNs were spherical and homogeneously dispersed. The average diameter of free SLNs and LWS-SLNs were 97 ± 1.4 and 127 ± 3.1 nm, respectively with high EE% (95.88 ± 3.29) and a DL of 22.72 ± 1.39 mg/mL of LWS-SLNs. The plain LWS could induce growth inhibition of A549 cells with IC50 of 17.99 ± 1.11, 13.37 ± 1.22, and 9.21 ± 1.15 µg/mL after 24, 48, and 72 h, respectively, while LWS-SLNs had more cytotoxic effects after 48 h (9.81 ± 1.3 µg/mL). Comet assay represented clear fragmentation in the chromatin of the treated cells. Besides, LWS-SLNs (13.37 ± 1.22 µg/mL) induced ∼52 % apoptosis and even necrosis after 48 h. The qPCR results showed an enhanced downregulation of Bcl-2 and upregulation of Casp 9 due to the treatment of A549 cells with LSW-SLNs. In conclusion, a stable formulation of LWS-SLN was prepared with good physicochemical features and long-term biological effects that candidate it for in vivo trials.

Natural polypeptides-based electrically conductive biomaterials for tissue engineering.

Fabrication of an appropriate scaffold is the key fundamental step required for a successful tissue engineering (TE). The artificial scaffold as extracellular matrix in TE has noticeable role in the fate of cells in terms of their attachment, proliferation, differentiation, orientation and movement. In addition, chemical and electrical stimulations affect various behaviors of cells such as polarity and functionality. Therefore, the fabrication approach and materials used for the preparation of scaffold should be more considered. Various synthetic and natural polymers have been used extensively for the preparation of scaffolds. The electrically conductive polymers (ECPs), moreover, have been used in combination with other polymers to apply electric fields (EF) during TE. In this context, composites of natural polypeptides and ECPs can be taken into account as context for the preparation of suitable scaffolds with superior biological and physicochemical features. In this review, we overviewed the simultaneous usage of natural polypeptides and ECPs for the fabrication of scaffolds in TE.

Antisense LNA-loaded nanoparticles of star-shaped glucose-core PCL-PEG copolymer for enhanced inhibition of oncomiR-214 and nucleolin-mediated therapy of cisplatin-resistant ovarian cancer cells.

We aimed to inhibit overexpressed oncomiR-214 in cisplatin (CIS)-resistant ovarian cancer (OC) and perform targeted therapy of sensitized cells using a novel polymeric drug delivery system (DDS). A system of nanoparticles (NPs) of star-shaped glucose-core polycaprolactone-polyethylene glycol (Glu-PCL-PEG) block copolymer containing cisplatin (CIS-PCL NPs) and locked nucleic acid (LNA) anti-miR-214 (LNA-PCL NPs) were prepared and anti-nucleolin aptamer was conjugated to the surface of prepared NPs to prepare Ap-CIS-PCL NPs and Ap-LNA-PCL NPs, respectively. The cancer-targeting ability of the NPs was confirmed and the CIS-resistant A2780 (A2780 R) cells were transfected with Ap-LNA-PCL NPs to inhibit oncomiR-214 and sensitize the cells to CIS. Next, the miR-214-inhibited cells were exposed to the Ap-CIS-NPs and the deracination efficiency of targeted DDS was evaluated. The oncomiR-214 in A2780 R cells were harnessed by Ap-LNA-PCL NPs, and nucleolin-mediated endocytosis of targeted polymeric DDSs containing CIS into miR-214-inhibited A2780 R cells caused enhanced apoptosis, which was further confirmed by apoptosis detection and evaluation of downstream genes expression. Targeted inhibition of miR-214 using the developed NPs containing LNA can decrease drug-resistant properties of cancer cells and may enhance the efficiency of targeted DDSs.

Electrically conductive biomaterials based on natural polysaccharides: Challenges and applications in tissue engineering.

Since the introduction of tissue engineering (TE) concept for repair or regeneration of failed tissues/organs, this novel interdisciplinary field has progressed significantly. In this context, cells, signal molecules, and scaffolds are the key fundamental elements which required for a successful TE. Among these, scaffold as an artificial extracellular matrix (ECM) has a prominent role in cell attachment, differentiation, orientation, proliferation, and new tissue formation. Moreover, stimulants such as electric field (EF) affect different aspects of cellular performances, including polarity, wound healing, division, and differentiation. In this respect, simultaneous usage of natural polysaccharides and electrically conductive polymers can be considered as a new strategy to produce composite biomaterials as suitable scaffolds with superior physicochemical and biological properties. This review focuses on the simultaneous usage of natural polysaccharides and electrically conductive polymers for the fabrication of bio-scaffold and investigation of their performance in TE.

AS1411 aptamer-decorated cisplatin-loaded poly(lactic-co-glycolic acid) nanoparticles for targeted therapy of miR-21-inhibited ovarian cancer cells.

AIM: The overexpression of miRNA-21 correlates with the cisplatin (CIS) resistance in the ovarian cancers. METHODS: AS1411 antinucleolin aptamer-decorated PEGylated poly(lactic-co-glycolic acid) nanoparticles containing CIS (Ap-CIS-NPs) and anti-miR-21 (Ap-anti-miR-21-NPs) were prepared, physicochemically investigated and their cancer-targeting ability was confirmed. CIS-resistant A2780 cells (A2780 R) were infected with anti-miR-21 using Ap-anti-miR-21-NPs to decrease the drug resistance and sensitize the cells to CIS. Afterward, miR-21-inhibited cells were exposed to the Ap-CIS-NPs. RESULTS: Ap-anti-miR-21-NPs could infect the A2780 R cells mainly through nucleolin-mediated endocytosis and inhibit the endogenous miR-21. Targeted delivery of CIS using Ap-CIS-NPs into the miR-21-inhibited cells caused an enhanced mortality. CONCLUSION: The targeted delivery of chemotherapeutics to the oncomiR-inhibited cells may find a robust application in cancer chemo/gene therapy.

Recent advances in aptamer-armed multimodal theranostic nanosystems for imaging and targeted therapy of cancer.

The side effects of chemotherapeutics during the course of cancer treatment limit their clinical outcomes. The most important mission of the modern cancer therapy modalities is the delivery of anticancer drugs specifically to the target cells/tissue in order to avoid/reduce any inadvertent non-specific impacts on the healthy normal cells. Nanocarriers decorated with a designated targeting ligand such as aptamers (Aps) and antibodies (Abs) are able to deliver cargo molecules to the target cells/tissue without affecting other neighboring cells, resulting in an improved treatment of cancer. For targeted therapy of cancer, different ligands (e.g., protein, peptide, Abs, Aps and small molecules) have widely been used in the development of different targeting drug delivery systems (DDSs). Of these homing agents, nucleic acid Aps show unique targeting potential with high binding affinity to a variety of biological targets (e.g., genes, peptides, proteins, and even cells and organs). Aps have widely been used as the targeting agent, in large part due to their unique 3D structure, simplicity in synthesis and functionalization, high chemical flexibility, low immunogenicity and toxicity, and cell/tissue penetration capability in some cases. Here, in this review, we provide important insights on Ap-decorated multimodal nanosystems (NSs) and discuss their applications in targeted therapy and imaging of cancer.