Co-Encapsulation of Violacein and Iron Oxide in Poly(lactic acid) Nanoparticles for Simultaneous Antibacterial and Anticancer Applications.

To date, the possibility of drug-resistant bacterial infections in hospitals and intensive care units comprises a significant concern especially for immunocompromised cancer patients. In the current study, violacein and superparamagnetic iron oxide nanoparticles were co-encapsulated in polylactic acid nanoparticles (vio-Fe3O4-PLA) and tested for their antimicrobial and anticancer activity. The loaded nanoparticles presented efficient saturation magnetization that rendered this nanosystem a promising candidate for magnetic targeting. Moreover, violacein released from the nanoparticles at 500 µg/mL successfully inhibited the growth of the "superbug" methicillin-resistant Staphylococcus aureus (MRSA) with an IC50 value of 595.8 µg/mL, while it did not prove effective against multi-drug-resistant Escherichia coli at concentrations of 10-1000 µg/mL. Finally, a concentration of 500 µg/mL of drug loaded magnetic nanoparticles induced an over 80% growth inhibition of glioblastoma and melanoma cancer cell lines with IC50 values of 221.30 and 201.60 µg/mL, respectively. Since bacterial infections are a key clinical problem for cancer patients due to their compromised immune systems, the presented results suggest that our system should be further studied for its simultaneous anti-bacterial and anti-cancer properties, as it comprises a promising strategy for combating bacterial infections and providing anticancer activity through magnetic-targeted delivery.

The Potential Anticancer Activity of 5-Fluorouracil Loaded in Cellulose Fibers Isolated from Rice Straw.

INTRODUCTION: Green-based materials have been increasingly studied to circumvent off-target cytotoxicity and other side-effects from conventional chemotherapy. MATERIALS AND METHODS: Here, cellulose fibers (CF) were isolated from rice straw (RS) waste by using an eco-friendly alkali treatment. The CF network served as an anticancer drug carrier for 5-fluorouracil (5-FU). The physicochemical and thermal properties of CF, pure 5-FU drug, and the 5-FU-loaded CF (CF/5-FU) samples were evaluated. The samples were assessed for in vitro cytotoxicity assays using human colorectal cancer (HCT116) and normal (CCD112) cell lines, along with human nasopharyngeal cancer (HONE-1) and normal (NP 460) cell lines after 72-hours of treatment. RESULTS: XRD and FTIR revealed the successful alkali treatment of RS to isolate CF with high purity and crystallinity. Compared to RS, the alkali-treated CF showed an almost fourfold increase in surface area and zeta potential of up to -33.61 mV. SEM images illustrated the CF network with a rod-shaped structure and comprised of ordered aggregated cellulose. TGA results proved that the thermal stability of 5-FU increased within the drug carrier. Based on UV-spectroscopy measurements for 5-FU loading into CF, drug loading encapsulation efficiency was estimated to be 83 ±0.8%. The release media at pH 7.4 and pH 1.2 showed a maximum drug release of 79% and 46%, respectively, over 24 hours. In cytotoxicity assays, CF showed almost no damage, while pure 5-FU killed most of the both normal and cancer cells. Impressively, the drug-loaded sample of CF/5-FU at a 250 µg/mL concentration demonstrated a 58% inhibition against colorectal cancer cells, but only a 23% inhibition against normal colorectal cells. Further, a 62.50 µg/mL concentration of CF/5FU eliminated 71% and 39% of nasopharyngeal carcinoma and normal nasopharyngeal cells, respectively. DISCUSSION: This study, therefore, showed the strong potential anticancer activity of the novel CF/5-FU formulations, warranting their further investigation.

Enzymatic Synthesis of Ricinoleyl Hydroxamic Acid Based on Commercial Castor Oil, Cytotoxicity Properties and Application as a New Anticancer Agent.

BACKGROUND: New anticancer agents that rely on natural/healthy, not synthetic/toxic, components are very much needed. METHODS: Ricinoleyl hydroxamic acid (RHA) was synthesized from castor oil and hydroxylamine using Lipozyme TL IM as a catalyst. To optimize the conversion, the effects of the following parameters were investigated: type of organic solvent, period of reaction, amount of enzyme, the molar ratio of reactants and temperature. The highest conversion was obtained when the reaction was carried out under the following conditions: hexane as a solvent; reaction period of 48 hours; 120 mg of Lipozyme TL IM/3 mmol oil; HA-oil ratio of 19 mmol HA/3 mmol oil; and temperature of 40°C. The cytotoxicity of the synthesized RHA was assessed using human dermal fibroblasts (HDF), and its application towards fighting cancer was assessed using melanoma and glioblastoma cancer cells over a duration of 24 and 48 hours. RESULTS: RHA was successfully synthesized  and it demonstrated strong anticancer activity against glioblastoma and melanoma cells at as low as a 1 µg/mL concentration while it did not demonstrate any toxicity against HDF cells. CONCLUSION: This is the first report on the synthesis of RHA with great potential to be used as a new anticancer agent.

Green Synthesis of Zeolite/Fe2O3 Nanocomposites: Toxicity & Cell Proliferation Assays and Application as a Smart Iron Nanofertilizer.

PURPOSE: The aim of this study was to prepare zeolite/iron (III) oxide nanocomposites (zeolite/Fe2O3-NCs) as a smart fertilizer to improve crop yield and soil productivity. METHODS: Zeolite/Fe2O3-NCs were successfully produced by loading of Fe2O3-NPs onto the zeolite surface using a quick green precipitation method. The production of zeolite/Fe2O3 nanocomposites was performed under a mild condition using environmentally friendly raw materials as a new green chemistry method. The product was characterized using several techniques such as near and far Fourier-transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: The results confirmed the formation of Fe2O3-NPs with mean particle sizes of 1.45, 2.19, and 2.20 nm on the surface of the zeolite per amount of 4, 7 and 12 wt% Fe2O3-NPs, respectively. Such results indicated that the size of the Fe2O3-NPs did not significantly change when Fe amounts increased from 7 to 12 wt% for the zeolite/Fe2O3-NCs. In terms of medical applications, in vitro cell studies demonstrated that zeolites and zeolite/Fe2O3-NCs were generally non-toxic to human fibroblast cells and significantly pernicious to human malignant melanoma cells. From MTS cytotoxicity assays, the concentration of Fe2O3 within the zeolite/Fe2O3-NCs that was effective at inhibiting the growth of malignant melanoma cells by 50% (the IC50 value) was ~14.9 wt%. The three types of nanocomposites were further tested as an iron smart nanofertilizer for the slow-release of iron ions. CONCLUSION: Advantages of this project include the production of non-toxic nanocomposites as a smart fertilizer to develop crops while the reaction involves the use of commercial and natural materials as low-cost raw materials with low energy usage due to a mild reaction condition, as well as the use of an environmentally friendly solvent (water) with no toxic residues.

Local Immunomodulation Using an Adhesive Hydrogel Loaded with miRNA-Laden Nanoparticles Promotes Wound Healing.

Chronic wounds are characterized by impaired healing and uncontrolled inflammation, which compromise the protective role of the immune system and may lead to bacterial infection. Upregulation of miR-223 microRNAs (miRNAs) shows driving of the polarization of macrophages toward the anti-inflammatory (M2) phenotype, which could aid in the acceleration of wound healing. However, local-targeted delivery of microRNAs is still challenging, due to their low stability. Here, adhesive hydrogels containing miR-223 5p mimic (miR-223*) loaded hyaluronic acid nanoparticles are developed to control tissue macrophages polarization during wound healing processes. In vitro upregulation of miR-223* in J774A.1 macrophages demonstrates increased expression of the anti-inflammatory gene Arg-1 and a decrease in proinflammatory markers, including TNF-α, IL-1ß, and IL-6. The therapeutic potential of miR-223* loaded adhesive hydrogels is also evaluated in vivo. The adhesive hydrogels could adhere to and cover the wounds during the healing process in an acute excisional wound model. Histological evaluation and quantitative polymerase chain reaction (qPCR) analysis show that local delivery of miR-223* efficiently promotes the formation of uniform vascularized skin at the wound site, which is mainly due to the polarization of macrophages to the M2 phenotype. Overall, this study demonstrates the potential of nanoparticle-laden hydrogels conveying miRNA-223* to accelerate wound healing.

Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival.

A primary goal in the management of burn wounds is early wound closure. The use of skin allografts represents a lifesaving strategy for severe burn patients, but their ultimate rejection limits their potential efficacy and utility. IL-6 is a major pleiotropic cytokine which critically links innate and adaptive immune responses. Here, we devised anti-IL-6 receptor eluting gelatin methacryloyl (GelMA) biomaterials (GelMA/anti-IL-6), which were implanted at the interface between the wound beds and skin allografts. Our visible light crosslinked GelMA/anti-IL-6 immunomodulatory biomaterial (IMB) demonstrated a stable kinetic release profile of anti-IL-6. In addition, the incorporation of anti-IL-6 within the GelMA hydrogel had no effect on the mechanical properties of the hydrogels. Using a highly stringent skin transplant model, the GelMA/anti-IL-6 IMB almost doubled the survival of skin allografts. The use of GelMA/anti-IL-6 IMB was far superior to systemic anti-IL-6 receptor treatment in prolonging skin allograft survival. As compared to the untreated control group, skin from the GelMA/anti-IL-6 IMB group contained significantly fewer alloreactive T cells and macrophages. Interestingly, the environmental milieu of the draining lymph nodes (DLNs) of the mice implanted with the GelMA/anti-IL-6 IMB was also considerably less pro-inflammatory. The percentage of CD4+ IFNγ+ cells was much lower in the DLNs of the GelMA/anti-IL-6 IMB group in comparison to the GelMA group. These data highlight the importance of localized immune delivery in prolonging skin allograft survival and its potential utility in treating patients with severe burns.

Current developments in green synthesis of metallic nanoparticles using plant extracts: a review.

Metal nanoparticles (MNPs) produced by green approaches have received global attention because of their physicochemical characteristics and their applications in the field of biotechnology. In recent years, the development of synthesizing NPs by plant extracts has become a major focus of researchers because of these NPs have low hazardous effect in the environment and low toxicity for the human body. Synthesized NPs from plants are not only more stable in terms of size and shape, also the yield of this method is higher than the other methods. Moreover, some of these MNPs have shown antimicrobial activity which is consistently confirmed in past few years. Plant extracts have been used as reducing agent and stabilizer of NPs in which we can reduce the toxicity in the environment as well as the human body only by not using chemical agents. Furthermore, the presence of some specific materials in plant extracts could be extremely helpful and effective for the human body; for instance, polyphenol, which may have antioxidant effects has the capability for capturing free radicals before they can react with other biomolecules and cause serious damages. In this article, we focused on of the most common plants which are regularly used to synthesize MNPs along with various methods for synthesizing MNPs from plant extracts.