Delivery of Natural Agents by Means of Mesoporous Silica Nanospheres as a Promising Anticancer Strategy

Natural prodrugs derived from different natural origins (e.g., medicinal plants, microbes, animals) have a long history in traditional medicine. They exhibit a broad range of pharmacological activities, including anticancer effects in vitro and in vivo. They have potential as safe, cost-effective treatments with few side effects, but are lacking in solubility, bioavailability, specific targeting and have short half-lives. These are barriers to clinical application. Nanomedicine has the potential to offer solutions to circumvent these limitations and allow the use of natural pro-drugs in cancer therapy. Mesoporous silica nanoparticles (MSNs) of various morphology have attracted considerable attention in the search for targeted drug delivery systems. MSNs are characterized by chemical stability, easy synthesis and functionalization, large surface area, tunable pore sizes and volumes, good biocompatibility, controlled drug release under different conditions, and high drug-loading capacity, enabling multifunctional purposes. In vivo pre-clinical evaluations, a significant majority of results indicate the safety profile of MSNs if they are synthesized in an optimized way. Here, we present an overview of synthesis methods, possible surface functionalization, cellular uptake, biodistribution, toxicity, loading strategies, delivery designs with controlled release, and cancer targeting and discuss the future of anticancer nanotechnology-based natural prodrug delivery systems

Nanomedicine as an Emerging Technology to Foster Application of Essential Oils to Fight Cancer

Natural prodrugs extracted from plants are increasingly used in many sectors, including the pharmaceutical, cosmetic, and food industries. Among these prodrugs, essential oils (EOs) are of particular importance. These biologically active volatile oily liquids are produced by medicinal and aromatic plants and characterized by a distinctive odor. EOs possess high anticancer, antibacterial, antiviral, and antioxidant potential but often are associated with low stability; high volatility; and a high risk of deterioration with exposure to heat, humidity, light, or oxygen. Furthermore, their bioavailability is limited because they are not soluble in water, and enhancements are needed to increase their potential to target specific cells or tissues, as well as for controlled release. Nanomedicine, the application of nanotechnology in medicine, may offer efficient solutions to these problems. The technology is based on creating nanostructures in which the natural prodrug is connected to or encapsulated in nanoparticles or submicron-sized capsules that ensure their solubility in water and their targeting properties, as well as controlled delivery. The potential of EOs as anticancer prodrugs is considerable but not fully exploited. This review focusses on the recent progress towards the practical application of EOs in cancer therapy based on nanotechnology applications

Green Synthesis of Controlled Shape Silver Nanostructures and Their Peroxidase, Catalytic Degradation, and Antibacterial Activity

Nanoparticles with unique shapes have garnered significant interest due to their enhanced surface area-to-volume ratio, leading to improved potential compared to their spherical counterparts. The present study focuses on a biological approach to producing different silver nanostructures employing Moringa oleifera leaf extract. Phytoextract provides metabolites, serving as reducing and stabilizing agents in the reaction. Two different silver nanostructures, dendritic (AgNDs) and spherical (AgNPs), were successfully formed by adjusting the phytoextract concentration with and without copper ions in the reaction system, resulting in particle sizes of ~300 ± 30 nm (AgNDs) and ~100 ± 30 nm (AgNPs). These nanostructures were characterized by several techniques to ascertain their physicochemical properties; the surface was distinguished by functional groups related to polyphenols due to plant extract that led to critical controlling of the shape of nanoparticles. Nanostructures performance was assessed in terms of peroxidase-like activity, catalytic behavior for dye degradation, and antibacterial activity. Spectroscopic analysis revealed that AgNDs demonstrated significantly higher peroxidase activity compared to AgNPs when evaluated using chromogenic reagent 3,3′,5,5′-tetramethylbenzidine. Furthermore, AgNDs exhibited enhanced catalytic degradation activities, achieving degradation percentages of 92.2% and 91.0% for methyl orange and methylene blue dyes, respectively, compared to 66.6% and 58.0% for AgNPs. Additionally, AgNDs exhibited superior antibacterial properties against Gram-negative E. coli compared to Gram-positive S. aureus, as evidenced by the calculated zone of inhibition. These findings highlight the potential of the green synthesis method in generating novel nanoparticle morphologies, such as dendritic shape, compared with the traditionally synthesized spherical shape of silver nanostructures. The synthesis of such unique nanostructures holds promise for various applications and further investigations in diverse sectors, including chemical and biomedical fields

Nanoformulation Composed of Ellagic Acid and Functionalized Zinc Oxide Nanoparticles Inactivates DNA and RNA Viruses

The COVID-19 pandemic has strongly impacted daily life across the globe and caused millions of infections and deaths. No drug therapy has yet been approved for the clinic. In the current study, we provide a novel nanoformulation against DNA and RNA viruses that also has a potential for implementation against COVID-19. The inorganic–organic hybrid nanoformulation is composed of zinc oxide nanoparticles (ZnO NPs) functionalized with triptycene organic molecules (TRP) via EDC/NHS coupling chemistry and impregnated with a natural agent, ellagic acid (ELG), via non-covalent interactions. The physicochemical properties of prepared materials were identified with several techniques. The hybrid nanoformulation contained 9.5 wt.% TRP and was loaded with up to 33.3 wt.% ELG. ELG alone exhibited higher cytotoxicity than both the ZnO NPs and nanoformulation against host cells. The nanoformulation efficiently inhibited viruses, compared to ZnO NPs or ELG alone. For H1N1 and HCoV-229E (RNA viruses), the nanoformulation had a therapeutic index of 77.3 and 75.7, respectively. For HSV-2 and Ad-7 (DNA viruses), the nanoformulation had a therapeutic index of 57.5 and 51.7, respectively. In addition, the nanoformulation showed direct inactivation of HCoV-229E via a virucidal mechanism. The inhibition by this mechanism was > 60%. Thus, the nanoformulation is a potentially safe and low-cost hybrid agent that can be explored as a new alternative therapeutic strategy for COVID-19

Co-Delivery System of Curcumin and Colchicine Using Functionalized Mesoporous Silica Nanoparticles Promotes Anticancer and Apoptosis Effects

Purpose: Many natural agents have a high anticancer potential, and their combination may be advantageous for improved anticancer effects. Such agents, however, often are not water soluble and do not efficiently target cancer cells, and the kinetics of their action is poorly controlled. One way to overcome these barriers is to combine natural agents with nanoparticles. Our aim in the current study was to fabricate an anticancer nanoformulation for co-delivery of two natural agents, curcumin (CR) and colchicine (CL), with a core-shell structure. Using cancer cell lines, we compared the anticancer efficacy between the combination and a nanoformulation with CL alone. Methods: For the single-drug nanoformulation, we used phosphonate groups to functionalize mesoporous silica nanoparticles (MSNs) and loaded the MSNs with CL. Additional loading of this nanoformulation with CR achieved the co-delivery format. To create the structure with a core shell, we selected a chitosan–cellulose mixture conjugated with targeting ligands of folic acid for the coating. For evaluating anticancer and apoptosis effects, we assessed changes in important genes and proteins in apoptosis (p53, caspase-3, Bax, Bcl-2) in several cell lines (MCF-7, breast adenocarcinoma; HCT-116, colon carcinoma; HOS, human osteosarcoma; and A-549, non–small cell lung cancer). Results: Nanoformulations were successfully synthesized and contained 10.9 wt.% for the CL single-delivery version and 18.1 wt.% for the CL+CR co-delivery nanoformulation. Anticancer effects depended on treatment, cell line, and concentration. Co-delivery nanoformulations exerted anticancer effects that were significantly superior to those of single delivery or free CL or CR. Anticancer effects by cell line were in the order of HCT-116 > A549 > HOS > MCF-7. The lowest IC50 value was obtained for the nanoformulation consisting of CL and CR coated with a polymeric shell conjugated with FA (equivalent to 4.1 ± 0.05 µg/mL). With dual delivery compared with the free agents, we detected strongly increased p53, caspase-3, and Bax expression, but inhibition of Bcl-2, suggesting promotion of apoptosis. Conclusions: Our findings, although preliminary, indicate that the proposed dual delivery nanoformulation consisting of nanocore: MSNs loaded with CL and CR and coated with a shell of chitosan–cellulose conjugated folic acid exerted strong anticancer and apoptotic effects with potent antitumor activity against HCT-116 colon cells. The effect bested CL alone. Evaluating and confirming the efficacy of co-delivery nanoformulations will require in vivo studies

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

Drug-Releasing Antibacterial Coating Made from Nano-Hydroxyapatite Using the Sonocoating Method

Medical implant use is associated with a risk of infection caused by bacteria on their surface. Implants with a surface that has both bone growth-promoting properties and antibacterial properties are of interest in orthopedics. In the current study, we fabricated a bioactive coating of hydroxyapatite nanoparticles on polyether ether ketone (PEEK) using the sonocoating method. The sonocoating method creates a layer by immersing the object in a suspension of nanoparticles in water and applying a high-power ultrasound. We show that the simple layer fabrication method results in a well-adhering layer with a thickness of 219 nm to 764 nm. Dropping cefuroxime sodium salt (Cef) antibiotic on the coated substrate creates a layer with a drug release effect and antibacterial activity against Staphylococcus aureus. We achieved a concentration of up to 1 mg of drug per cm2 of the coated substrate. In drug release tests, an initial burst was observed within 24 h, accompanied by a linear stable release effect. The drug-loaded implants exhibited sufficient activity against S. aureus for 24 and 168 h. Thus, the simple method we present here produces a biocompatible coating that can be soaked with antibiotics for antibacterial properties and can be used for a range of medical implants

Novel delivery system with a dual–trigger release of savory essential oil by mesoporous silica nanospheres and its possible targets in leukemia cancer cells: in vitro study

Abstract Introduction Essential oils (EOs) are complex structures and possess several pharmacological effects. Nanomedicine offers a solution for their major limitations, including poor solubility, volatility, and non–controlled release, preventing their clinical use. Methods Here, we developed a novel delivery system by nanoformulations that were prepared by impregnating savory essential oil (SA) into mesoporous silica nanoparticles (MSNs). The nanoformulations were characterized and examined for their anticancer activities on cancer cells (HepG2 liver and HL60 leukemia cells) and MRC5 normal cells. We further tested the mechanisms of action and possible molecular targets against HL60 cells. Results The results demonstrated that SA was governed by nanoformulations under the dual–trigger release of pH/glutathione, and it typically fit the Korsmeyer–Peppas kinetic model. The nanoformulations enhanced the anticancer effect against HepG2 cells and HL60 cells compared to SA but were less cytotoxic to MRC5 normal cells and regulated various molecular pathways of apoptosis. Most importantly, new results were obtained on the genetic regulation principle through the high inhibition of long noncoding RNAs (HOTAIR, HULC, CCAT1, and H19) and matrix metalloproteinases (MMP–2 and MMP–9), providing a novel leukemia target. Conclusions These results suggest potential impacts for nanoformulations composed of SA with a sustained release pattern controlled by dual–trigger release of pH/GSH that enhanced anticancer cells. This approach may offer a new route for using EOs as new targets for cancers and open the door for deep preclinical investigations