Therapeutic role of biogenic silver and gold nanoparticles against a DMH-induced colon cancer model.

Colorectal cancer (CRC) ranks third among fatal diseases afflicting mankind globally due to the shortage of primary detection methods and appropriate choice of drugs. Moreover, current treatments such as chemo drugs and radiotherapies create adverse effects and lead to drug resistance. In this context, recent advances in nanomedicine offer novel clinical solutions for colon cancer therapy. The current study denotes the therapeutic roles of biogenic Abutilon indicum silver and gold nanoparticles (AIAgNPs and AIAuNPs) against a 1, 2-dimethyl hydrazine (DMH)-induced CRC in Wistar rats. Following treatment of nanoparticles (NPs), the CRC rats showed great localization of AIAgNPs and AIAuNPs in colon tumors shown by ICP-OES, indicating their bioavailability. The AIAgNPs and AIAuNPs significantly enhanced cellular antioxidant enzyme levels including catalase, SOD, GSH, GPx and reduced lipid peroxidation (LPO) compared to the standard drug paclitaxel. AIAgNPs and AIAuNPs revealed significant protection against metastasis compared to paclitaxel shown in the histopathological study. The important CRC signaling molecules of the Wnt pathway, the ß-catenin and Tcf-4 levels were significantly downregulated in AIAgNPs and AIAuNPs treated CRC rats compared to paclitaxel. Furthermore, the expression levels of cleaved apoptotic caspase-9, -8, and - 3 and lamins were significantly upregulated in AIAgNPs and AIAuNPs treated CRC rats compared to paclitaxel. This preclinical study provides substantial insights into the anti-colon cancer roles of biogenic NPs and gives an idea for targeting different cancers.

The Dynamic Inflammatory Tissue Microenvironment: Signality and Disease Therapy by Biomaterials.

Tissue regeneration is an active multiplex process involving the dynamic inflammatory microenvironment. Under a normal physiological framework, inflammation is necessary for the systematic immunity including tissue repair and regeneration as well as returning to homeostasis. Inflammatory cellular response and metabolic mechanisms play key roles in the well-orchestrated tissue regeneration. If this response is dysregulated, it becomes chronic, which in turn causes progressive fibrosis, improper repair, and autoimmune disorders, ultimately leading to organ failure and death. Therefore, understanding of the complex inflammatory multiple player responses and their cellular metabolisms facilitates the latest insights and brings novel therapeutic methods for early diseases and modern health challenges. This review discusses the recent advances in molecular interactions of immune cells, controlled shift of pro- to anti-inflammation, reparative inflammatory metabolisms in tissue regeneration, controlling of an unfavorable microenvironment, dysregulated inflammatory diseases, and emerging therapeutic strategies including the use of biomaterials, which expand therapeutic views and briefly denote important gaps that are still prevailing.

Green synthesized silver nanoparticles: Catalytic dye degradation, in vitro anticancer activity and in vivo toxicity in rats.

In this study, silver nanoparticles were synthesized (AgNPs) using aqueous rhizome extract of Acorus calamus (ACRE) and evaluated their in vitro anticancer activity and in vivo toxicity in a Wistar rat model. The synthesized AgNPs showed good catalytic activity against different organic pollutant dyes. In vitro cytotoxic effects of AgNPs were assessed in Hep2, COLO 205 and SH-SY5Y cells using MTT assay. Further, the apoptotic changes induced by AgNPs in more susceptible Hep2 cells were observed through AO/EB, DCFH-DA, Rhodamine 123, PI/DAPI staining, oxidative stress markers and Western blotting. In vivo toxicity study revealed substantial alterations in the levels of serum biochemical markers including AST, ALT, LDH and inflammatory markers such as TNF-α and IL-6 on day 29 when rats treated with AgNPs as compared to control, however, these levels were restored to normal at the end of washout period on day 89. No remarkable changes were observed in liver oxidative stress enzymes. ICP-OES analysis indicated bio-distribution of silver in spleen (5.67 µg/g) and liver (4.98 µg/g) in rats treated with 10 mg/kg b.w of AgNPs on day 29 and elimination of silver from all organs was observed at the end of washout period on day 89. Histopathological analysis revealed no significant changes in kidney, spleen, lungs, heart, testis and brain with 5 and 10 mg/kg b.w of AgNP. However, 10 mg/kg b.w of AgNPs showed moderate degree of cell swelling and vacuolar degeneration in liver and these alterations were reverted back to normal at the end of washout period. Findings from this study signify green synthesized AgNPs at low concentrations might be useful in many ways with ecofriendly nature.

In vivo bio-distribution, clearance and toxicity assessment of biogenic silver and gold nanoparticles synthesized from Abutilon indicum in Wistar rats.

This study reports the bio-distribution and clearance of Abutilon indicum silver and gold nanoparticles (AIAgNPs and AIAuNPs) in Wistar rats. Rats in different groups were orally administered with 5 and 10 mg/Kg BW of AIAgNPs and AIAuNPs (size 1-25 nm) for 28 days and few were maintained until 58 days of washout period. Serum biochemical parameters were not changed significantly at both doses of AIAuNPs and at lower concentration of AIAgNPs. But, with 10 mg/Kg BW of AIAgNPs rats showed elevated levels of AST, ALP and ALT on day 29, however, these levels were restored to normal after washout period. Liver oxidative stress markers were not altered with the treatment of AIAgNPs and AIAuNPs. ICP-OES analysis indicated bio-distribution of Ag and Au more in liver, kidney and spleen on day 29 and was found cleared on day 59. Histological analysis of nine vital organs indicated normal tissue architecture at both doses of AIAuNPs and lower dose of AIAgNPs. While the rats treated with higher dose of AIAgNPs showed mild liver sinusoid cell swelling on day 29, which also was recovered on day 59. Findings of this preclinical study indicate biocompatible nature of biogenic nanoparticles supporting their future biomedical applications.

Green synthesized nano silver: Synthesis, physicochemical profiling, antibacterial, anticancer activities and biological in vivo toxicity.

Green synthesis of nanoparticles using plants is gaining much interest in recent years. Anyway, intricate details on the role of phytochemicals involved in capping and stabilization of nanoparticles in diminishing toxicity and enhancing therapeutic potential are required. In this study, Ficus religiosa silver nanoparticles (FRAgNPs) were synthesized using Ficus religiosa leaf extract (FRLE) and characterized. The FRAgNPs showed good antibacterial activity and also cytotoxic effect in different cancer cell lines. Induction of apoptotic cell death was confirmed by various staining techniques, increased expression of cleaved caspases-8, 9, 3, lamin, PARP and oxidative stress markers in A549 and Hep2 cells. The in vivo studies performed in rats revealed significant increase in serum levels of AST, ALT, and LDH, TNF-α and IL-6 on day 29 following oral administration of FRAgNPs. However, these levels reverted back to normal at the end of wash out period on day 89. ICP-OES analysis revealed accumulation of silver in liver, brain and lungs on day 29 with respective concentration of 4.77, 3.94 and 3.043µg/g tissue. However, complete elimination of silver was observed on day 89. Histological analysis performed in vital organs indicated pathological changes only in liver which was also normalized after 89days.

Polyphenol stabilized colloidal gold nanoparticles from Abutilon indicum leaf extract induce apoptosis in HT-29 colon cancer cells.

Green synthesized gold nanoparticles have received substantial attention owing to their biomedical applications, particularly in cancer therapy. Although anticancer activities of green synthesized gold nanoparticles have been reported earlier, the underlying mechanism behind their anticancer activity is still to be understood. The present study, describes the green synthesis of Abutilon indicum gold nanoparticles (AIGNPs) from Abutilon indicum leaf extract (AILE) and their cytotoxic mechanism in colon cancer cells. Dimensions of spherical shaped AIGNPs were found to be in the range of 1-20nm as determined by TEM. GC-MS and FTIR analysis indicated the presence of polyphenolic groups in AILE, which might have been involved in the stabilization of AIGNPs. In vitro free radical scavenging analysis revealed the radical quenching activity of AIGNPs. Further, the AIGNPs exhibited cytotoxicity in HT-29 colon cancer cells with IC50 values of 210 and 180µg/mL after 24 and 48h. This was mediated through nuclear morphological changes and cell membrane damage as evidenced by acridine orange/ethidium bromide, propidium iodide and AnnexinV-Cy3 staining methods. Mechanism of the observed cytotoxicity of AIGNPs was explained on the basis of increased levels of reactive oxygen species and simultaneous reduction in cellular antioxidants, which might have caused mitochondrial membrane potential loss, DNA damage and G1/S phase cell cycle arrest. Expression of cleaved Caspase-9, Caspase-8, Caspase-3, Lamin A/C and PARP, provided the clues for the induction of intrinsic and extrinsic apoptosis pathways in AIGNPs treated HT-29 cells. The study provides a preliminary guidance towards the development of colon cancer therapy using green synthesized gold nanoparticles.

Catalytic and biological activities of green silver nanoparticles synthesized from Plumeria alba (frangipani) flower extract.

Herein, we report the green synthesis of silver nanoparticles using Plumeria alba (frangipani) flower extract (FFE) and their biological applications. The formation of frangipani silver nanoparticles (FSNPs) was confirmed by UV-visible spectroscopy and characterized by DLS particle size analyzer, SEM/EDAX, FTIR, TGA/DSC and XRD. The synthesized spherical FSNPs were found to be 36.19nm in size as determined by DLS particle size analyzer. EDAX data and XRD pattern of FSNPs confirmed the presence and face-centered cubic (fcc) phase structure of silver. The bioactive groups C-C and C-N present in FFE were involved in the formation of FSNPs as identified by FTIR analysis. FSNPs exhibited powerful catalytic activity by reducing 4-nitrophenol to 4-aminophenol within 8min and the other organic dyes namely methylene blue and ethidium bromide were moderately degraded. Biological activities of FSNPs are evaluated by means of antioxidant, antibacterial and cytotoxic effect. Antioxidant potential of FSNPs was assessed by various in vitro assays in which they exhibited moderate antioxidant activity. The antibacterial effect of FSNPs was tested in two different pathogenic bacterial strains and their bacteriostatic effect was confirmed by growth kinetic study in Escherichia coli. The cytotoxic effect of FSNPs in COLO 205 was analyzed by MTT assay and the IC50 concentration was found at 5.5 and 4µg/ml respectively after 24 and 48h of incubation. Cytotoxic effect of FSNPs in COLO 205 cells was associated with the loss of membrane integrity and chromatin condensation which might have played a crucial role in the induction of apoptosis as evidenced in AO/EB staining.

Biogenic silver nanoparticles from Abutilon indicum: their antioxidant, antibacterial and cytotoxic effects in vitro.

Green synthesis of silver nanoparticles using biological entities is gaining interest because of their potential applications in nano-medicine. Herein, we report the biological synthesis of Abutilon indicum silver nanoparticles (AIAgNPs) using aqueous Abutilon indicum leaf extract (AILE) and evaluation of their biological applications. TEM analysis revealed that the spherical biogenic AIAgNPs were found to be between 5 and 25 nm in size. The bioactive phyto-constituents such are condensed tannins of AILE were found to play a key role in the reduction and capping of AIAgNPs. The biological properties of AIAgNPs were premeditated as free radical scavenging activity, antibacterial effect and anti-proliferative activity. AIAgNPs were found to exhibit good free radical scavenging activities and the intense zone of inhibition displayed by them in six different pathogenic species indicate the potential antibacterial effect. Further, AIAgNPs showed a dose dependant anti-proliferative effect against COLO 205 (human colon cancer) and MDCK (normal) cells with an IC50 of 3 and 4 µg/mL and 100 and 75 µg/mL, respectively after 24 and 48 h. The morphological changes, chromatin condensation and membrane potential loss induced by AIAgNPs were evidenced by AO/EB and AnnexinV-Cy3 staining. The mitochondrial membrane potential (MMP) loss and G1/S transition cell cycle arrest in COLO 205 cells was evidenced in rhodamine123 staining and FACS analysis. The high levels of ROS as shown in DCF-DA staining could have played a major role in DNA fragmentation and eventually lead to apoptosis. The mode of action through the induction apoptosis by AIAgNPs in COLO 205 cells is exciting with promising application of nano-materials in biomedical research.

Biological activities of green silver nanoparticles synthesized with Acorous calamus rhizome extract.

Nanomedicine utilize biocompatible nanomaterials for diagnostic and therapeutic purposes. This study reports the synthesis of silver nanoparticles using aqueous rhizome extract of Acorus calamus (ACRE) and evaluation of antioxidant, antibacterial as well as anticancer effects of synthesized A. calamus silver nanoparticles (ACAgNPs). The formation of ACAgNPs was confirmed by UV-visible spectroscopy and their average size was found to be 31.83 nm by DLS particle size analyzer. Scanning electron micrograph (SEM) revealed spherical shape of ACAgNPs and energy dispersive spectroscopy (EDX) data showed the presence of metallic silver. Fourier transform infrared spectroscopy (FTIR) analysis indicated the presence of phenol/alcohol, aromatic amine and carbonyl groups in ACRE that were involved in reduction and capping of nanoparticles. ACRE and ACAgNPs exhibited substantial free radical quenching ability in various in vitro antioxidant assays performed in this study. ACAgNPs also displayed appreciable antibacterial activity against three different pathogenic bacteria and the growth kinetic study with Escherichia coli designated the inhibition of bacterial growth at the log phase. The cytotoxic effect of ACAgNPs was assessed by MTT assay in HeLa and A549 cells. The IC50 value of ACAgNPs respectively after 24 and 48 h was found to be 92.48 and 69.44 µg/ml in HeLa cells and in A549 cells it was 53.2 and 32.1 µg/ml. Apoptotic cell death in ACAgNPs treated cells was indicated by acridine orange/ethidium bromide (AO/EB) and annexinV-Cy3 staining techniques. Staining with propidium iodide (PI) and 4', 6-diamidino-2-phenylindole, dihydrochloride (DAPI) also confirmed nuclear changes such as condensation and fragmentation. Further, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed distribution of ACAgNPs treated cells in the late apoptotic stage. These findings emphasize that such biocompatible green nanoparticles with multifaceted biological activities may find their applications in the field of nanomedicine.