Poly(sodium acrylate)-Modified Magnetite Nanoparticles for Separation of Heavy Metals from Aqueous Solutions.

Two types of magnetite nanoparticles: unmodified (Fe3O4 NPs), and modified with poly(sodium acrylate) (Fe3O4/PSA NPs) were synthesized by the co-precipitation method and characterized using different techniques: X-ray diffraction (XRD), transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), Brunauer-Emmett-Teller (BET) adsorption, Fourier-transform infrared spectroscopy (FTIR). Additionally, magnetic properties and the effect of pH on the zeta potential were analyzed for both types of nanoparticles. Magnetites were used as adsorbents for seven heavy metal ions (Zn(II), Cu(II), Ni(II), Cd(II), Pb(II), Cr(III), Cr(VI)) within the pH range of 3-7. Research revealed nanometric particle sizes, a specific surface area of 140-145 m2/g, and superparamagnetic properties of both tested materials. Moreover, the presence of PSA functional groups in modified magnetite was confirmed, which lowered the pH of the isoelectric point. Both types of magnetite were effective metal ion adsorbents, with metal cations more effectively removed on Fe3O4/PSA NPs and Cr(VI) anions on Fe3O4 NPs. The adsorption of most of the examined cations (performed at pH = 5) can be well described by the Langmuir isotherm model, whereas the adsorption of Cr(VI) ions on modified magnetite correlated better with the Freundlich model. The Dubinin-Radushkevich model confirmed that chemisorption is the predominant process. The adsorption of all metal ions was well-characterized by the pseudo-second-order kinetic model.

Targeted Nano-Drug Delivery of Colchicine against Colon Cancer Cells by Means of Mesoporous Silica Nanoparticles.

Antimitotics are important anticancer agents and include the natural alkaloid prodrug colchicine (COL). However, a major challenge of using COL as an anticancer drug is its cytotoxicity. We developed a novel drug delivery system (DDS) for COL using mesoporous silica nanoparticles (MSNs). The MSNs were functionalized with phosphonate groups, loaded with COL, and coated with folic acid chitosan-glycine complex. The resulting nanoformulation, called MSNsPCOL/CG-FA, was tested for action against cancer and normal cell lines. The anticancer effect was highly enhanced for MSNsPCOL/CG-FA compared to COL. In the case of HCT116 cells, 100% inhibition was achieved. The efficiency of MSNsPCOL/CG-FA ranked in this order: HCT116 (colon cancer) > HepG2 (liver cancer) > PC3 (prostate cancer). MSNsPCOL/CG-FA exhibited low cytotoxicity (4%) compared to COL (~60%) in BJ1 normal cells. The mechanism of action was studied in detail for HCT116 cells and found to be primarily intrinsic apoptosis caused by an enhanced antimitotic effect. Furthermore, a contribution of genetic regulation (metastasis-associated lung adenocarcinoma transcript 1 (MALAT 1), and microRNA (mir-205)) and immunotherapy effects (angiopoietin-2 (Ang-2 protein) and programmed cell death protein 1 (PD-1) was found. Therefore, this study shows enhanced anticancer effects and reduced cytotoxicity of COL with targeted delivery compared to free COL and is a novel method of developing cancer immunotherapy using a low-cost small-molecule natural prodrug.

Effective Targeting of Colon Cancer Cells with Piperine Natural Anticancer Prodrug Using Functionalized Clusters of Hydroxyapatite Nanoparticles.

Targeted drug delivery offers great opportunities for treating cancer. Here, we developed a novel anticancer targeted delivery system for piperine (Pip), an alkaloid prodrug derived from black pepper that exhibits anticancer effects. The tailored delivery system comprises aggregated hydroxyapatite nanoparticles (HAPs) functionalized with phosphonate groups (HAP-Ps). Pip was loaded into HAPs and HAP-Ps at pH 7.2 and 9.3 to obtain nanoformulations. The nanoformulations were characterized using several techniques and the release kinetics and anticancer effects investigated in vitro. The Pip loading capacity was >20%. Prolonged release was observed with kinetics dependent on pH, surface modification, and coating. The nanoformulations fully inhibited monolayer HCT116 colon cancer cells compared to Caco2 colon cancer and MCF7 breast cancer cells after 72 h, whereas free Pip had a weaker effect. The nanoformulations inhibited ~60% in HCT116 spheroids compared to free Pip. The Pip-loaded nanoparticles were also coated with gum Arabic and functionalized with folic acid as a targeting ligand. These functionalized nanoformulations had the lowest cytotoxicity towards normal WI-38 fibroblast cells. These preliminary findings suggest that the targeted delivery system comprising HAP aggregates loaded with Pip, coated with gum Arabic, and functionalized with folic acid are a potentially efficient agent against colon cancer.

In vivo and in vitro study of a novel nanohydroxyapatite sonocoated scaffolds for enhanced bone regeneration.

There still remains a need for new methods of healing large bone defects, i.e., gaps in bone tissue that are too big to naturally heal. Bone regrowth scaffolds can fill the bone gap and enhance the bone regeneration by providing cells with a support to for new tissue formation. Coating of the scaffolds surface with nanocrystalline hydroxyapatite may enhance the osteoinductivity or osteoconductivity of such scaffolds. Here we present the sonocoating method to coat scaffolds with bioactive hydroxyapatite nanoparticles. We show a method, where the material to be coated is immersed in a colloidal suspension of nanoparticles with mean sizes of 10 nm and 43 nm in water, and high-power ultrasound waves are applied to the suspension for 15 min at 30 °C. High power ultrasounds lead to growth of cavitation bubbles in liquid, which implode at a critical size. The implosion energy propels the nanoparticles towards the material surface, causing their attachment to the scaffold. Using this technique, we produced a uniform layer of nanohydroxyapatite particles of thickness in the range 200 to 300 nm on two types of scaffolds: a porous ß-TCP ceramic scaffold and a 3D-printed scaffold made of PCL fibers. In vivo tests in rabbits confirmed that the novel coating strongly stimulated new bone tissue formation, with new bone tissue occupying 33% for the nHAP-coated PCL scaffold and 68% for the nHAP-coated ß-TCP after a 3-month test. The sonocoating method leads to formation of a bioactive layer on the scaffolds at temperature close to room temperature, very short time and in water. It is a green technological process, promising for bone tissue regeneration applications.

Dendrimer based theranostic nanostructures for combined chemo- and photothermal therapy of liver cancer cells in vitro.

Here we report the synthesis of multifunctional nanocarriers based on PAMAM dendrimers generation (G) 4.0, 5.0 and 6.0 fixed to polydopamine (PDA) coated magnetite nanoparticles (Fe3O4). Synthesized nanoplatforms were characterized by transmission electron microscopy (TEM), the electrokinetic (zeta) potential, Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and magnetic resonance imaging (MRI). Further, we show as a proof of concept that nanocarriers functionalized with G 5.0 could be successfully applied in combined chemo- and photothermal therapy (CT-PTT) of the liver cancer cells. The cooperative effect of the modalities mentioned above led to higher mortality of cancer cells when compared to their individual performance. Moreover, the performed in vitro studies revealed that the application of dual therapy triggered the desired cell death mechanism-apoptosis. Furthermore, performed tests using Magnetic Resonance Imaging (MRI) showed that our materials have competitive contrast properties. Overall, the functionality of dendrimers has been extended by merging them with magnetic nanoparticles resulting in multifunctional hybrid nanostructures that are promising smart drug delivery system for cancer therapy.

Folic acid-conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action.

Naturally derived prodrugs have a wide range of pharmacological activities, including anticancer, antioxidant, and antiviral effects. However, significant barriers inhibit their use in medicine, e.g. their hydrophobicity. In this comprehensive study, we investigated simple and effective nanoformulations consisting of amine-functionalized and conjugated with folic acid (FA) mesoporous silica nanoparticles (MSNs). Two types of MSNs were studied: KCC- 1, with mean size 324 nm and mean pore diameter 3.4 nm, and MCM - 41, with mean size 197 and pore diameter 2 nm. Both types of MSNs were loaded with three anticancer prodrugs: curcumin, quercetin, and colchicine. The nanoformulations were tested to target in vitro human hepatocellular carcinoma cells (HepG2) and HeLa cancer cells. The amine-functionalized and FA-conjugated curcumin-loaded, especially KCC-1 MSNs penetrated all cells organs and steadily released curcumin. The FA-conjugated MSNs displayed higher cellular uptake, sustained intracellular release, and cytotoxicity effects in comparison to non-conjugated MSNs. The KCC-1 type MSNs carrying curcumin displayed the highest anticancer activity. Apoptosis was induced through specific signaling molecular pathways (caspase-3, H2O2, c-MET, and MCL-1). The nanoformulations displayed also an enhanced antioxidant activity compared to the pure forms of the prodrugs, and the effect depended on the time of release, type of MSN, prodrug, and assay used. FA-conjugated MSNs carrying curcumin and other safe natural prodrugs offer new possibilities for targeted cancer therapy.

Effect of Microwave Radiation Power on the Size of Aggregates of ZnO NPs Prepared Using Microwave Solvothermal Synthesis.

This paper reports the possibility of changing the size of zinc oxide nanoparticles (ZnO NPs) aggregates through a change of synthesis parameters. The effect of the changed power of microwave heating on the properties of ZnO NPs obtained by the microwave solvothermal synthesis from zinc acetate dissolved in ethylene glycol was tested for the first time. It was found that the size of ZnO aggregates ranged from 60 to 120 nm depending on the power of microwave radiation used in the synthesis of ZnO NPs. The increase in the microwave radiation power resulted in the reduction of the total synthesis time with simultaneous preservation of the constant size and shape of single ZnO NPs, which were synthesized at a pressure of 4 bar. All the obtained ZnO NPs samples were composed of homogeneous spherical particles that were single crystals with an average size of 27 ± 3 nm with a developed specific surface area of 40 m²/g and the skeleton density of 5.18 ± 0.03 g/cm³. A model of a mechanism explaining the correlation between the size of aggregates and the power of microwaves was proposed. This method of controlling the average size of ZnO NPs aggregates is presented for the first time and similar investigations are not found in the literature.