Therapeutic Advancements in Metal and Metal Oxide Nanoparticle-Based Radiosensitization for Head and Neck Cancer Therapy.

Although radiation therapy (RT) is one of the mainstays of head and neck cancer (HNC) treatment, innovative approaches are needed to further improve treatment outcomes. A significant challenge has been to design delivery strategies that focus high doses of radiation on the tumor tissue while minimizing damage to surrounding structures. In the last decade, there has been increasing interest in harnessing high atomic number materials (Z-elements) as nanoparticle radiosensitizers that can also be specifically directed to the tumor bed. Metallic nanoparticles typically display chemical inertness in cellular and subcellular systems but serve as significant radioenhancers for synergistic tumor cell killing in the presence of ionizing radiation. In this review, we discuss the current research and therapeutic efficacy of metal nanoparticle (MNP)-based radiosensitizers, specifically in the treatment of HNC with an emphasis on gold- (AuNPs), gadolinium- (AGdIX), and silver- (Ag) based nanoparticles together with the metallic oxide-based hafnium (Hf), zinc (ZnO) and iron (SPION) nanoparticles. Both in vitro and in vivo systems for different ionizing radiations including photons and protons were reviewed. Finally, the current status of preclinical and clinical studies using MNP-enhanced radiation therapy is discussed.

Improving Radiotherapy Response in the Treatment of Head and Neck Cancer.

The application of radiotherapy to the treatment of cancer has existed for over 100 years. Although its use has cured many, much work remains to be done to minimize side effects, and in-field tumor recurrences. Resistance of the tumor to a radiation-mediated death remains a complex issue that results in local recurrence and significantly decreases patient survival. Here, we review mechanisms of radioresistance and selective treatment combinations that improve the efficacy of the radiation that is delivered. Further investigation into the underlying mechanisms of radiation resistance is warranted to develop not just novel treatments, but treatments with improved safety profiles relative to current radiosensitizers. This review is written in memory and honor of Dr. Peter Stambrook, an avid scientist and thought leader in the field of DNA damage and carcinogenesis, and a mentor and advocate for countless students and faculty.

Effect of Digitalized Previsit Imagery on Behavior of Children in the Dental Operatory.

Aim and objective: The present study was aimed to determine the impact of exposure to digitalized previsit imagery technique on the anticipatory dental anxiety levels of children. Design: 40 children, aged 4-8 years requiring noninvasive dental treatment were included in the study. Preintervention anxiety levels were assessed using Venham picture test (VPT) in the waiting room and randomly divided into two groups. The study group was exposed to the digitalized previsit imagery technique which included a customized cartoon video of dental operatory and the concerned pediatric dentist in his/her own voice through WhatsApp messenger. The other group was dealt with the conventional approach using verbal and nonverbal communication. Postintervention anxiety was assessed in both the groups and the difference was compared. Result: A significant difference in anticipatory dental anxiety was found between the two groups (p<0.001) using SPSS software. There was no marked relation of age and sex with the reduction of anxiety levels after exposure to digitalized previsit imagery. Conclusion: The idea of digitalizing previsit imagery can be a time saving approach which is helpful in managing anxious children before entering the dental operatory. How to cite this article: Reddy RE, Merum K, Mudusu SP, et al. Effect of Digitalized Previsit Imagery on Behavior of Children in the Dental Operatory. Int J Clin Pediatr Dent 2021;14(S-2):S124-S130.

Design and Characterization of Cyclosporine A-Loaded Nanofibers for Enhanced Drug Dissolution.

Despite widespread use as an immunosuppressant, the therapeutic efficacy of the undecapeptide cyclosporine A (CyA) is compromised when given by the oral route because of the innate hydrophobicity of the drug molecule, potentially leading to poor aqueous solubility and bioavailability. The aim of this study was to develop and characterize nanofibers based on the water-miscible polymer polyvinylpyrrolidone (PVP), incorporating CyA preloaded into polymeric surfactants so as to promote micelle formation on hydration; therefore, this approach represents the novel combination of three dissolution enhancement methodologies, namely solid dispersion technology, micellar systems, and nanofibers with enhanced surface area. The preparation of the nanofibers was performed in two steps. First, mixed micelles composed of the water-soluble vitamin E derivative d-α-tocopheryl poly(ethylene glycol) 1000 succinate and the amphiphilic triblock polymer Pluronic F127 (Poloxamer 407) were prepared. The micelles were characterized in terms of size, surface charge, drug loading, and encapsulation efficiency using transmission electron microscopy, dynamic light scattering, Fourier-transform infrared spectroscopy, high-performance liquid chromatography, and scanning electron and atomic force microscopy analysis. Nanofibers composed of PVP and the drug-loaded surfactant system were then prepared via electrospinning, with accompanying thermal, spectroscopic, and surface topological analysis. Dissolution studies indicated an extremely rapid dissolution profile for the fibers compared to the drug alone, while wettability studies also indicated a marked decrease in contact angle compared to the drug alone. Overall, the new approach appears to offer a viable means for considerably improving the dissolution of the hydrophobic peptide CyA, with associated implications for improved oral bioavailability.

Brevifoliol ester induces apoptosis in prostate cancer cells by activation of caspase pathway.

Prostate cancer is fourth most abundant cancer type around the globe. Brevifoliol, a rearranged taxoid from Taxus walllichiana needles has been derivatized as C5 esters using Steglich esterification reaction. Seventeen diverse analogues were evaluated against a panel of human cancer cell lines by MTT assay. Among these, two of the semi-synthetic analogues, that is, 13 and 16 exhibited potent cytotoxicity, selectively against PC-3, prostate cancer cell lines. In cell cycle analysis, analogue 13 induced S and G2/M phase arrest and induced apoptosis by activating caspase-3. Compound 13 showed moderate efficacy in in-vivo Ehrlich ascites carcinoma in Swiss albino mice. Further, compound 13 was found to be safe in Swiss albino mice up to 1,000 mg/kg dose in acute oral toxicity. Brevifoliol ester 13 may further be optimized for better efficacy.

Combined effect of cellulose nanocrystal and reduced graphene oxide into poly-lactic acid matrix nanocomposite as a scaffold and its anti-bacterial activity.

In the present study, cellulose nanocrystals (CNCs) and reduced graphene oxide (rGO) were successfully synthesized via acid hydrolysis and modified Hummer's method, respectively. Further, the synthesized CNCs and rGO were incorporated into poly-lactic acid (PLA) matrix using solution casting method utilizing different weight (wt.) % of CNCs (nanofiller) and rGO. The successful synthesis of various nanoformulations were confirmed by several characterization techniques including Transmission Electron Microscopy (TEM), Field-Emission Scanning Electron Microscopy (FE-SEM) and Fourier Transform Infrared Spectroscopy (FTIR) analysis. Hydrophilicity measurement of the film was done by wettability analysis. The mechanical property evaluation of scaffold showed considerable increased tensile strength of PLA/CNC/rGO nanocomposite upto 23%, with increase in elongation at break (εb) indicating the ductile behavior of nanocomposite as compare to pristine PLA. The distinct anti-bacterial efficacy of PLA/CNC/rGO nanocomposite film was found against both Gram positive Staphylococcus aureus (S.aureus) and Gram negative Escherichia coli. (E. coli) bacterial strains respectively. Furthermore the in-vitro cell based cytotoxicity assay showed negligible cytotoxicity of fibroblast cell line (NIH-3T3) upon treatment with nanocomposite film. Therefore, the as fabricated nanocomposite film possesses considerable potential in biomedical as well as in food packaging applications.

Fabrication of electrospun poly(ethylene oxide)-poly(capro lactone) composite nanofibers for co-delivery of niclosamide and silver nanoparticles exhibits enhanced anti-cancer effects in vitro.

An intrinsic property of many anticancer drugs including niclosamide is poor water solubility, which hindered their translation from laboratory to clinics. In an effort to enhance their water solubility and bioavailability, we have developed simplistic strategies based on the solvent evaporation and amorphous solid dispersion methods. Among various solvent evaporation methods, electrospinning was adopted in the present work. Poly(ethylene oxide) (PEO) was selected as the polymeric solid dispersion matrix of the drug based on various advantageous properties of PEO. Moreover PEO could also serve as a template for the in situ synthesis of silver nanoparticles (Ag NPs). Furthermore the co-delivery of multiple anticancer drugs within a nanocarrier is a promising approach to overcome the drug resistance and to achieve synergistic therapy. To achieve this goal, the drugs (niclosamide (nic)) and Ag NPs were loaded separately and together (nic@Ag NPs) into the nanofiber. The as-prepared various formulations of composite nanofibers were well-characterized by different techniques. The in vitro release and kinetic studies suggest the sustained release of niclosamide which followed Fickian diffusion kinetics. The anticancer potential of the drugs alone and the nic@Ag NPs loaded nanofibers were evaluated by MTT assay against A549 (lung carcinoma) and MCF-7 (breast carcinoma) cell lines. The co-delivery of anticancer drugs nic@Ag NPs from nanofibers displayed superior anticancer potential in vitro when compared to nic alone or Ag NPs composite nanofibers. Additionally nic@Ag NPs showed better therapeutic efficacy against MCF-7 cells. To confirm the mechanism of cell death by nic@Ag NP composite nanofibers on MCF-7 cells, various cell based assays were done. Our finding clearly explains that a combination of drugs with the diverse anticancer mechanism remarkably improved the therapeutic potential of drugs. Therefore, the nic@Ag NPs composite nanofiber as a co-delivery system might have potential applications in combination cancer therapy.

Perturbation of cellular mechanistic system by silver nanoparticle toxicity: Cytotoxic, genotoxic and epigenetic potentials.

Currently the applications of silver nanoparticles (Ag NPs) are gaining overwhelming response due to the advancement of nanotechnology. However, only limited information is available with regard to their toxicity mechanism in different species. It is very essential to understand the complete molecular mechanism to explore the functional and long term applications of Ag NPs. Ag NPs could be toxic at cellular, subcellular, biomolecular, and epigenetic levels. Toxicity effects induced by Ag NPs have been evaluated using numerous in vitro and in vivo models, but still there are contradictions in interpretations due to disparity in methodology, test endpoints and several other model parameters which needs to be considered. Thus, this review article focuses on the progressive elucidation of molecular mechanism of toxicity induced by Ag NPs in various in vitro and in vivo models. Apart from these, this review also highlights the various ignored factors which are to be considered during toxicity studies.

Antibacterial activity and mechanism of Ag-ZnO nanocomposite on S. aureus and GFP-expressing antibiotic resistant E. coli.

Emergence of multi-resistant organisms (MROs) leads to ineffective treatment with the currently available medications which pose a great threat to public health and food technology sectors. In this regard, there is an urgent need to strengthen the present therapies or to look over for other potential alternatives like use of "metal nanocomposites". Thus, the present study focuses on synthesis of silver-zinc oxide (Ag-ZnO) nanocomposites which will have a broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria. Ag-ZnO nanocomposites of varied molar ratios were synthesized by simple microwave assisted reactions in the absence of surfactants. The crystalline behavior, composition and morphological analysis of the prepared powders were evaluated by X-ray diffraction, infrared spectroscopy, field emission scanning electron microscopy (FE-SEM) and atomic absorption spectrophotometry (AAS). Particle size measurements were carried out by transmission electron microscopy (TEM). Staphylococcus aureus and recombinant green fluorescent protein (GFP) expressing antibiotic resistant Escherichia coli were selected as Gram-positive and Gram-negative model systems respectively and the bactericidal activity of Ag-ZnO nanocomposite was studied. The minimum inhibitory concentration (MIC) and minimum killing concentration (MKC) of the nanocomposite against the model systems were determined by visual turbidity analysis and optical density analysis. Qualitative and quantitative assessments of its antibacterial effects were performed by fluorescent microscopy, fluorescent spectroscopy and Gram staining measurements. Changes in cellular morphology were examined by atomic force microscopy (AFM), FE-SEM and TEM. Finally, on the basis of the present investigation and previously published reports, a plausible antibacterial mechanism of Ag-ZnO nanocomposites was proposed.

Ferritin nanocages: a novel platform for biomedical applications.

Ferritin is a ubiquitous iron storage protein responsible for maintaining the iron homeostasis in living organism and thereby protects the cell from oxidative damage. The ferritin protein cages have been used as a reaction vessel for the synthesis of various non-native metallic nanoparticles inside its core and also used as a nanocarrier for various applications. Lack of suitable non-viral carrier for targeted delivery of anticancer drugs and imaging agents is the major problem in cancer therapy and diagnosis. The pH dependent reversible assembling and disassembling property of ferritin renders it as a suitable candidate for encapsulating a variety of anticancer drugs and imaging probes. Ferritins external surface is chemically and genetically modifiable which can serve as attachment site for tumor specific targeting peptides or moieties. Recent studies, further establishes ferritin as a multifunctional nanocarrier for targeted cancer diagnosis and therapy. Moreover, the biological origin of these protein cages makes it a biocompatible nanocarrier that stabilizes and protects the enclosed particles from the external environment without provoking any toxic or immunogenic responses. This review mainly focuses on the application of ferritin nanocages as a novel non-viral nanocarrier for cancer therapy and it also highlights various biomedical applications of ferritin nanocages.