Recent Advances in Biopolymeric Composite Materials for Tissue Engineering and Regenerative Medicines: A Review.

The polymeric composite material with desirable features can be gained by selecting suitable biopolymers with selected additives to get polymer-filler interaction. Several parameters can be modified according to the design requirements, such as chemical structure, degradation kinetics, and biopolymer composites' mechanical properties. The interfacial interactions between the biopolymer and the nanofiller have substantial control over biopolymer composites' mechanical characteristics. This review focuses on different applications of biopolymeric composites in controlled drug release, tissue engineering, and wound healing with considerable properties. The biopolymeric composite materials are required with advanced and multifunctional properties in the biomedical field and regenerative medicines with a complete analysis of routine biomaterials with enhanced biomedical engineering characteristics. Several studies in the literature on tissue engineering, drug delivery, and wound dressing have been mentioned. These results need to be reviewed for possible development and analysis, which makes an essential study.

A Dual-Antigen Enzyme-Linked Immunosorbent Assay Allows the Assessment of Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Seroprevalence in a Low-Transmission Setting.

Estimates of seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have been hampered by inadequate assay sensitivity and specificity. Using an enzyme-linked immunosorbent assay-based approach that combines data about immunoglobulin G responses to both the nucleocapsid and spike receptor binding domain antigens, we show that excellent sensitivity and specificity can be achieved. We used this assay to assess the frequency of virus-specific antibodies in a cohort of elective surgery patients in Australia and estimated seroprevalence in Australia to be 0.28% (95% Confidence Interval, 0-1.15%). These data confirm the low level of transmission of SARS-CoV-2 in Australia before July 2020 and validate the specificity of our assay.

Antileishmanial activity and cytotoxicity of ZnO-based nano-formulations.

INTRODUCTION: Nanoparticles (NPs) can be toxic due to their nano-range sizes. Zinc oxide (ZnO) has good biocompatibility and is commercially used in cosmetics. Moreover, ZnO NPs have potential biomedical uses, but their safety remains unclear. METHODS: A range of doped ZnO NPs was evaluated for antileishmanial activity and in vitro toxicity in brine shrimp and human macrophages, and N-doped ZnO NPs were evaluated for in vivo toxicity in male BALB/C mice. N-doped ZnO NPs were administered via two routes: intra-peritoneal injection and topically as a paste. The dosages were 10, 50, and 100 mg/kg/day for 14 days. RESULTS: Topical administration was safe at all dosages, but intra-peritoneal injection displayed toxicity at higher doses, namely, 50 and 100 mg/kg/day. The pathological results for the i.p. dose groups were mild to severe degenerative changes in parenchyma cells, increases in Kupffer cells, disappearance of hepatic plates, increases in cell size, ballooning, cytoplasmic changes, and nuclear pyknosis in the liver. Kidney histology was also altered in the i.p. administration group (dose 100 mg/kg/day), with inflammatory changes in the focal area. We associate pathological abnormalities with the presence of doped ZnO NPs at the diseased site, which was verified by PIXE analysis of the liver and kidney samples of the treated and untreated mice groups. CONCLUSION: The toxicity of the doped ZnO NPs can serve as an essential determinant for the effects of ZnO NPs on environmental toxicity and can be used for guidelines for safer use of ZnO-based nanomaterials in topical treatment of leishmaniasis and other biomedical applications.

PEGylated doped- and undoped-TiO2 nanoparticles for photodynamic Therapy of cancers.

Titanium dioxide has been widely known for its phototoxicity in the environmental context, but little is known for its use in the photodynamic therapy of cancers. Previous studides have shown the hazardous effects of undoped-titanium dioxide nanoparticles (undoped-TiO2 NPs) in the ecosystem; however, it remains to explore the effect of polyethylene glycol (PEG) conjugation and doping of metal and non-metal on the photodynamic activity of TiO2. Here we report the synthesis, characterizations, and applications of doped- and undoped-TiO2 NPs stabilized by PEG in the photodynamic therapy of cancers. Our results demonstrate that in vitro PEG-NPs significantly reduced the survival of human cervical cancer cells (HeLa) upon solar and ultraviolet (UV) radiations. We found that doping of the metal (cobalt) and non-metal (nitrogen) onto TiO2 nanocrystals enhanced the photoactivation of doped-TiO2 NPs in the visible/near infrared (Vis/NIR) region, but these nanocrystals were revealed by cytotoxicity assays to be less potent in killing cancer cells compared to PEGylated undoped-TiO2. The significant photodynamic effect was shown by PEGylated undoped-TiO2 synthesized through the sol-gel method with 75% killing of HeLa cells at 5.5 µg/mL concentrations in exposure to UV or sunlight radiations. In vitro cytotoxicity was measured by Sulforhodamine B (SRB) and 3-(4, 5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assays after irradiations with IR, UV, and sunlight for 15-30 minutes (min). All the synthesized NPs were characterized by XRD, AFM, SEM, EDX and DRS chemical analysis. Taken together, our data demonstrate that water-soluble PEGylated TiO2 NPs maybe a good candidate for the photodynamic therapy of cervical cancer cells. Our data propose that the use of PEG surfactant can enhance the potency of already available photochemical therpeutic agents.

Paclitaxel loaded magnetic nanocomposites with folate modified chitosan/carboxymethyl surface; a vehicle for imaging and targeted drug delivery.

In this study, Paclitaxel (PTX) containing, bovine serum albumin (BSA) nanoparticles were fabricated via a simple approach. Folic acid (FA) was conjugated to chitosan (CS)/carboxymethyl cellulose (CMC) through an esterification reaction to produce BSA-CS-FA or BSA-CMC-FA conjugates. NiFe2O4 noncore (NFs) and PTX were loaded through a heat treatment and by a diffusion process. NFs-BSA-CS and NFs-BSA-CMC-FA with size of about 80nm, showed superior transversal R2 relaxation rate of 349 (mM)-1s-1 along with folate receptor-targeted and magnetically directed functions. NFs-BSA-CS-FA or NFs-BSA-CS-FA were found stable and biocompatible. Application of an external magnetic field effectively enhanced the PTX release from PTX-NFs-BSA-CS-FA or PTX-NFs-BSA-CS-FA and hence tumor inhibition rate. This study validate that NFs-BSA-CS-FA or NFs-BSA-CMC-FA and PTX-NFs-BSA-CS-FA or PTX-NFs-BSA-CS-FA are suitable systems for tumor diagnosis and therapy.

Microwave-assisted green synthesis of superparamagnetic nanoparticles using fruit peel extracts: surface engineering, T 2 relaxometry, and photodynamic treatment potential.

Superparamagnetic iron oxide nanoparticles (SPIONs) have the potential to be used as multimodal imaging and cancer therapy agents due to their excellent magnetism and ability to generate reactive oxygen species when exposed to light. We report the synthesis of highly biocompatible SPIONs through a facile green approach using fruit peel extracts as the biogenic reductant. This green synthesis protocol involves the stabilization of SPIONs through coordination of different phytochemicals. The SPIONs were functionalized with polyethylene glycol (PEG)-6000 and succinic acid and were extensively characterized by X-ray diffraction analysis, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, atomic force microscopy, Rutherford backscattering spectrometry, diffused reflectance spectroscopy, fluorescence emission, Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, and magnetization analysis. The developed SPIONs were found to be stable, almost spherical with a size range of 17-25 nm. They exhibited excellent water dispersibility, colloidal stability, and relatively high R 2 relaxivity (225 mM(-1) s(-1)). Cell viability assay data revealed that PEGylation or carboxylation appears to significantly shield the surface of the particles but does not lead to improved cytocompatibility. A highly significant increase of reactive oxygen species in light-exposed samples was found to play an important role in the photokilling of human cervical epithelial malignant carcinoma (HeLa) cells. The bio-SPIONs developed are highly favorable for various biomedical applications without risking interference from potentially toxic reagents.

"Smart" nickel oxide based core-shell nanoparticles for combined chemo and photodynamic cancer therapy.

We report "smart" nickel oxide nanoparticles (NOPs) as multimodal cancer therapy agent. Water-dispersible and light-sensitive NiO core was synthesized with folic acid (FA) connected bovine serum albumin (BSA) shell on entrapped doxorubicin (DOX). The entrapped drug from NOP-DOX@BSA-FA was released in a sustained way (64 hours, pH=5.5, dark conditions) while a robust release was found under red light exposure (in 1/2 hour under λmax=655 nm, 50 mW/cm(2), at pH=5.5). The cell viability, thiobarbituric acid reactive substances and diphenylisobenzofuran assays conducted under light and dark conditions revealed a high photodynamic therapy potential of our construct. Furthermore, we found that the combined effect of DOX and NOPs from NOP-DOX@BSA-FA resulted in cell death approximately eightfold high compared to free DOX. We propose that NOP-DOX@BSA-FA is a potential photodynamic therapy agent and a collective drug delivery system for the systemic administration of cancer chemotherapeutics resulting in combination therapy.

Photo-induced Leishmania DNA degradation by silver-doped zinc oxide nanoparticle: an in-vitro approach.

Recently, the authors reported newly synthesised polyethylene glycol (PEG)ylated silver (9%)-doped zinc oxide nanoparticle (doped semiconductor nanoparticle (DSN)) which has high potency for killing Leishmania tropica by producing reactive oxygen species on exposure to sunlight. The current report is focused on Leishmania DNA interaction and damage caused by the DSN. Here, we showed that the damage to Leishmania DNA was indirect, as the DSN was unable to interact with the DNA in intact Leishmania cell, indicating the incapability of PEGylated DSN to cross the nucleus barrier. The DNA damage was the result of high production of singlet oxygen on exposure to sunlight. The DNA damage was successfully prevented by singlet oxygen scavenger (sodium azide) confirming involvement of the highly energetic singlet oxygen in the DNA degradation process.

Annihilation of Leishmania by daylight responsive ZnO nanoparticles: a temporal relationship of reactive oxygen species-induced lipid and protein oxidation.

Lipid and protein oxidation are well-known manifestations of free radical activity and oxidative stress. The current study investigated extermination of Leishmania tropica promastigotes induced by lipid and protein oxidation with reactive oxygen species produced by PEGylated metal-based nanoparticles. The synthesized photodynamic therapy-based doped and nondoped zinc oxide nanoparticles were activated in daylight that produced reactive oxygen species in the immediate environment. Lipid and protein oxidation did not occur in dark. The major lipid peroxidation derivatives comprised of conjugated dienes, lipid hydroperoxides, and malondialdehyde whereas water, ethane, methanol, and ethanol were found as the end products. Proteins were oxidized to carbonyls, hydroperoxides, and thiol degrading products. Interestingly, lipid hydroperoxides were produced by more than twofold of the protein hydroperoxides, indicating higher degradation of lipids compared to proteins. The in vitro evidence represented a significant contribution of the involvement of both lipid and protein oxidation in the annihilated antipromastigote effect of nanoparticles.

Visible-light-responsive ZnCuO nanoparticles: benign photodynamic killers of infectious protozoans.

Human beings suffer from several infectious agents such as viruses, bacteria, and protozoans. Recently, there has been a great interest in developing biocompatible nanostructures to deal with infectious agents. This study investigated benign ZnCuO nanostructures that were visible-light-responsive due to the resident copper in the lattice. The nanostructures were synthesized through a size-controlled hot-injection process, which was adaptable to the surface ligation processes. The nanostructures were then characterized through transmission electron microscopy, X-ray diffraction, diffused reflectance spectroscopy, Rutherford backscattering, and photoluminescence analysis to measure crystallite nature, size, luminescence, composition, and band-gap analyses. Antiprotozoal efficiency of the current nanoparticles revealed the photodynamic killing of Leishmania protozoan, thus acting as efficient metal-based photosensitizers. The crystalline nanoparticles showed good biocompatibility when tested for macrophage toxicity and in hemolysis assays. The study opens a wide avenue for using toxic material in resident nontoxic forms as an effective antiprotozoal treatment.

Novel ZnO:Ag nanocomposites induce significant oxidative stress in human fibroblast malignant melanoma (Ht144) cells.

The use of photoactive nanoparticles (NPs) such as zinc oxide (ZnO) and its nanocomposites has become a promising anticancer strategy. However, ZnO has a low photocatalytic decomposition rate and the incorporation of metal ions such as silver (Ag) improves their activity. Here different formulations of ZnO:Ag (1, 3, 5, 10, 20 and 30% Ag) were synthesized by a simple co-precipitation method and characterized by powder X-ray diffraction, scanning electron microscopy, Rutherford back scattering and diffuse reflectance spectroscopy for their structure, morphology, composition and optical band gap. The NPs were investigated with regard to their different photocatalytic cytotoxic effects in human malignant melanoma (HT144) and normal (HCEC) cells. The ZnO:Ag nanocomposites killed cancer cells more efficiently than normal cells under daylight exposure. Nanocomposites having higher Ag content (10, 20 and 30%) were more toxic compared to low Ag content (1, 3 and 5%). For HT144, under daylight exposure, the IC50 values were ZnO:Ag (10%): 23.37 µg/mL, ZnO:Ag (20%): 19.95 µg/mL, and ZnO:Ag (30%): 15.78 µg/mL. ZnO:Ag (30%) was toxic to HT144 (IC50: 23.34 µg/mL) in dark as well. The three nanocomposites were further analyzed with regard to their ability to generate reactive oxygen species (ROS) and induce lipid peroxidation. The particles led to an increase in levels of ROS at cytotoxic concentrations, but only HT144 showed strongly induced MDA level. Finally, NPs were investigated for the ROS species they generated in vitro. A highly significant increase of (1)O2 in the samples exposed to daylight was observed. Hydroxyl radical species, HO(•), were also generated to a lesser extent. Thus, the incorporation of Ag into ZnO NPs significantly improves their photo-oxidation capabilities. ZnO:Ag nanocomposites could provide a new therapeutic option to selectively target cancer cells.

PEGylated silver doped zinc oxide nanoparticles as novel photosensitizers for photodynamic therapy against Leishmania.

We describe daylight responsive silver (Ag) doped semiconductor nanoparticles of zinc oxide (DSNs) for photodynamic therapy (PDT) against Leishmania. The developed materials were characterized by X-ray diffraction analysis (XRD), Rutherford backscattering (RBS), diffused reflectance spectroscopy (DRS), and band-gap analysis. The Ag doped semiconductor nanoparticles of zinc oxide were PEGylated to enhance their biocompatibility. The DSNs demonstrated effective daylight response in the PDT of Leishmania protozoans, through the generation of reactive oxygen species (ROS) with a quantum yield of 0.13 by nondoped zinc oxide nanoparticles (NDSN) whereas 0.28 by DSNs. None of the nanoparticles have shown any antileishmanial activity in dark, confirming that only ROS produced in the daylight were involved in the killing of leishmanial cells. Furthermore, the synthesized nanoparticles were found biocompatible. Using reactive oxygen species scavengers, cell death was attributable mainly to 77-83% singlet oxygen and 18-27% hydroxyl radical. The nanoparticles caused permeability of the cell membrane, leading to the death of parasites. Further, the uptake of nanoparticles by Leishmania cells was confirmed by inductively coupled plasma atomic emission spectroscopy (ICP-AES). We believe that these DSNs are widely applicable for the PDT of leishmaniasis, cancers, and other infections due to daylight response.

Synthesis and bioactivities of silver nanoparticles capped with 5-amino-ß-resorcylic acid hydrochloride dihydrate.

BACKGROUND: Conjugated and drug loaded silver nanoparticles are getting an increased attention for various biomedical applications. Nanoconjugates showed significant enhancement in biological activity in comparison to free drug molecules. In this perspective, we report the synthesis of bioactive silver capped with 5-Amino-ß-resorcylic acid hydrochloride dihydrate (AR). The in vitro antimicrobial (antibacterial, antifungal), enzyme inhibition (xanthine oxidase, urease, carbonic anhydrase, α-chymotrypsin, cholinesterase) and antioxidant activities of the developed nanostructures was investigated before and after conjugation to silver metal. RESULTS: The conjugation of AR to silver was confirmed through FTIR, UV-vis and TEM techniques. The amount of AR conjugated with silver was characterized through UV-vis spectroscopy and found to be 9% by weight. The stability of synthesized nanoconjugates against temperature, high salt concentration and pH was found to be good. Nanoconjugates, showed significant synergic enzyme inhibition effect against xanthine and urease enzymes in comparison to standard drugs, pure ligand and silver. CONCLUSIONS: Our synthesized nanoconjugate was found be to efficient selective xanthine and urease inhibitors in comparison to Ag and AR. On a per weight basis, our nanoconjugates required less amount of AR (about 11 times) for inhibition of these enzymes.

Nanomaterials in combating cancer: therapeutic applications and developments.

The development of novel nanomaterials and their use in biomedicine has received much attention in recent years. Significant advances have been made in the synthesis of nanomaterials with controlled geometry, physicochemical properties, surface charge, and surface tailoring with bioactive polymers. These successful efforts have resulted in improved biocompatibility and active targeting of tumour tissues, leading to the development of a diverse range of nanomaterials that can recognize cancers, deliver anticancer drugs and destroy tumours by a variety of therapeutic techniques. The focus of this review is to provide an overview of the nanomaterials that have been devised for the detection and treatment of various types of cancer, as well as to underline the emerging possibilities of nanomaterials for applications in anticancer therapy. FROM THE CLINICAL EDITOR: In this comprehensive review, the current state-of-the art of nanomaterials for cancer diagnosis and treatment is presented. Emerging possibilities and future concepts are discussed as well.

Brine shrimp lethality assay 'an effective prescreen': microwave-assisted synthesis, BSL toxicity and 3DQSAR studies-based designing, docking and antitumor evaluation of potent chalcones.

CONTEXT: In the course of searching potential antitumor agents from a library of chalcones synthesized under microwave irradiations, the brine shrimp lethality (BSL) assay and a 3D structure-activity relationship (3DQSAR) studies were followed by the antitumor evaluation of most potent analogues. OBJECTIVE: The objective of the current study was to effectively use the BSL assay for the identification of potential cytotoxic analogues from a set of compounds. METHODS: We applied the comparative molecular field analysis (CoMFA) and devised 3DQSAR on 33 synthesized chalcones leading to prediction of five related compounds with improved activity. The scope of BSL assay for the prediction of antitumor potency was tested through the in vitro antitumor studies against six human tumor cell-lines, docking studies and the tubulin-polymerization assay. RESULTS: The newly designed compounds 34-38 displayed very promising cytotoxic potency. From our results, the BSL toxicity, antitumor efficacy and docking outcomes could be easily co-related. CONCLUSION: The study draws a very good relationship between a simple, inexpensive, and bench-top BSL assay and the antitumor potential of the cytotoxic compounds. Devising the CoMFA analysis helped in designing chalcones with improved cytotoxic potential as displayed through their BSL and cytotoxic activity against human tumor cell lines. The studies are noteworthy as such comprehensive studies were never performed before on the BSL assay. The present studies widen the scope of the BSL model that may prove quite helpful as a preliminary screen in the antitumor drug designing and synthesis expeditions.

Hepatoprotection by chemical constituents of the marine brown alga Spatoglossum variabile: a relation to free radical scavenging potential.

CONTEXT: In the course of searching hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine brown alga Spatoglossum variabile Figaro et DE Notar (Dictyoaceae) against CCl4-induced liver damage in Wistar rats was investigated. The compounds were first investigated for in vitro radical scavenging potential and were also tested for ß-glucuronidase inhibition to further explore the relationship between hepatoprotection and antiradical potential. METHODS: The compounds cinnamic acid esters 1 and 2 and aurone derivatives 3 and 4 were first investigated for in vitro radical scavenging potential against 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), and superoxide anion radicals. In vivo hepatoprotective studies were performed in seven groups (n = 6) of Wistar rats. The test groups were pretreated with compounds (10 mg/kg body weight, po) orally for 30 min before the intraperitoneal administration of a dose of 20% CCl4 diluted with dietary cooking oil. Moreover, compounds were also tested for ß-glucuronidase inhibition to explore the relationship between hepatoprotection and radical scavenging potential. RESULTS: The test compounds 1-4 were found to exhibit antiradical activity against 1,1-diphenyl-2-picrylhydrazyl radicals with IC50 values ranging between 54 and 138 µM, whereas aurone derivatives 3 and 4 additionally exhibited superoxide anion scavenging effects with IC50 values of 95 and 87 µM, respectively. In addition, these compounds were found to be weak inhibitors of xanthine oxidase (IC50 ≥1000 µM). In animal model, pretreatment with compounds 2-4 significantly blocked the CCl4-induced increase in the levels of the serum biochemical markers. CONCLUSION: It appears that the hepatoprotection afforded by these compounds was mainly due to their radical scavenging activity that protected the cells from the free radicals generated by CCl4-induced hepatotoxicity.

Combinatorial synthesis, lead identification, and antitumor study of a chalcone-based positional-scanning library.

A 175-member chalcone library was designed and synthesized from seven differently substituted acetophenones (A(1)-A(7)) and 25 differently substituted aryl or heteroaryl aldehydes (B(1)-B(25)). Potential lead compounds were identified by deconvolution of a two-dimensional library matrix via positional scanning, and the members of the most-active sub-libraries were synthesized and screened against crown-gall tumors with the aid of the potato-disc assay. The resulting hits gave rise to significant antitumor activities, with no antibacterial effect on the tumor-producing bacterium Agrobacterium tumefaciens. Two identified lead structures, (2E)-3-(2-chlorophenyl)-1-phenylprop-2-en-1-one (A(1)B(9)) and the hydroxy analogue (2E)-3-(2-chlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (A(2)B(9)), are promising candidates to be developed into highly effective anticancer chemotherapeutics.

Combinatorial synthesis and antibacterial evaluation of an indexed chalcone library.

A 120-membered chalcone library has been designed and prepared from six differently substituted acetophenones (A1-A6) and 20 benzaldehydes (B1-B20). The library was subjected to biological studies targeted against six bacterial strains. For the identification of the most-active member(s) of the library, the so-called indexed or positional-scanning method was applied. Six out of 26 sub-libraries, i.e., AL1-AL6, were synthesized by keeping the acetophenone moiety A fixed and using equimolar quantities of the 20 different benzaldehydes. The remaining 20 sub-libraries BL1-BL20 were prepared by keeping the benzaldehyde B component fixed and varying the six acetophenones (Table 1). The bactericidal activities of the resulting sub-libraries were tested and used as indices to the rows or columns of a two-dimensional matrix. Finally, parallel synthesis of 24 specific members with the highest-expected antibacterial activities, present in two sub-libraries, was carried out. These chalcones were screened again, and the results were exploited for establishing the structure-activity relationship (SAR) and the identification of the lead compound, which turned out to be 1,3-bis(2-hydroxyphenyl)prop-2-en-1-one (A2B2) in terms of activity towards Staphylococcus aureus and Bacillus subtilis (Tables 5-7).