Metagenomic analysis unveils the microbial landscape of pancreatic tumors.

The composition of resident microbes in the human body is linked to various diseases and their treatment outcomes. Although studies have identified pancreatic ductal adenocarcinoma (PDAC)-associated bacterial communities in the oral and gut samples, herein, we hypothesize that the prevalence of microbiota in pancreatic tumor tissues is different as compared with their matched adjacent, histologically normal appearing tissues, and these microbial molecular signatures can be highly useful for PDAC diagnosis/prognosis. In this study, we performed comparative profiling of bacterial populations in pancreatic tumors and their respective adjacent normal tissues using 16S rRNA-based metagenomics analysis. This study revealed a higher abundance of Proteobacteria and Actinomycetota in tumor tissues compared with adjacent normal tissues. Interestingly, the linear discriminant analysis (LDA) scores unambiguously revealed an enrichment of Delftia in tumor tissues, whereas Sphingomonas, Streptococcus, and Citrobacter exhibited a depletion in tumor tissues. Furthermore, we analyzed the microbial composition between different groups of patients with different tumor differentiation stages. The bacterial genera, Delftia and Staphylococcus, were very high at the G1 stages (well differentiated) compared with G2 (well to moderate/moderately differentiated) and G3/G4 (poorly differentiated) stages. However, the abundance of Actinobacter and Cloacibacterium was found to be very high in G2 and G3, respectively. Additionally, we evaluated the correlation of programmed death-ligand (PDL1) expression with the abundance of bacterial genera in tumor lesions. Our results indicated that three genera such as Streptomyces, Cutibacterium, and Delftia have a positive correlation with PD-L1 expression. Collectively, these findings demonstrate that PDAC lesions harbor relatively different microbiota compared with their normal tumor adjacent tissues, and this information may be helpful for the diagnosis and prognosis of PADC patients.

Coating a Self-Assembly Nanoconstruct with a Neutrophil Cell Membrane Enables High Specificity for Triple Negative Breast Cancer Treatment.

Breast cancer is one of the most commonly diagnosed cancers in American women. Triple negative breast cancer is among the most advanced and aggressive forms of breast cancer. Treatment options are limited for such cancers, making chemotherapy a convenient and effective treatment. Although these therapies can reduce morbidity and mortality, it is often followed by systemic side effects or relapse. Nanoparticles (NPs) have been considered for drug delivery approaches due to their ability to target various disease sites. Herein, we aim to develop a biomimetic NP construct (cell membrane-cloaked NPs) that exhibits specific affinity with triple negative breast cancer cells. In this regard, we designed biomimetic supramolecular nanoconstructs composed of a poly(vinyl pyrrolidone)-tannic acid (PVP-TA NPs/ PVT NPs) core and biofunctionalized with neutrophil cell membranes (PVT-NEU NPs). In this study, we have synthesized a PVT-NEU NP construct, characterized it, and evaluated it for improved targeting and therapeutic benefits in in vitro and in vivo models. Analysis of PVT-NEU NPs confirms the presence of the core of PVP-TA NPs coated with activated human neutrophil membranes. The study results confirmed that PVT-NEU NPs demonstrated an enhanced interaction and targeting with the tumor cells, thus improving the therapeutic activity of a model therapeutic agent (paclitaxel). Altogether, this study suggests the potential of biomimetic NPs as a promising therapeutic option for targeted drug delivery for advanced-stage breast cancer and other similar diseased conditions.

PEG-functionalized magnetic nanoparticles for drug delivery and magnetic resonance imaging applications.

PURPOSE: Polyethylene glycol (PEG) functionalized magnetic nanoparticles (MNPs) were tested as a drug carrier system, as a magnetic resonance imaging (MRI) agent, and for their ability to conjugate to an antibody. METHODS: An iron oxide core coated with oleic acid (OA) and then with OA-PEG forms a water-dispersible MNP formulation. Hydrophobic doxorubicin partitions into the OA layer for sustained drug delivery. The T(1) and T(2) MRI contrast properties were determined in vitro and the circulation of the MNPs was measured in mouse carotid arteries. An N-hydroxysuccinimide group (NHS) on the OA-PEG-80 was used to conjugate the amine functional group on antibodies for active targeting in the human MCF-7 breast cancer cell line. RESULTS: The optimized formulation had a mean hydrodynamic diameter of 184 nm with an ~8 nm iron-oxide core. The MNPs enhance the T(2) MRI contrast and have a long circulation time in vivo with 30% relative concentration 50 min post-injection. Doxorubicin-loaded MNPs showed sustained drug release and dose-dependent antiproliferative effects in vitro; the drug effect was enhanced with transferrin antibody-conjugated MNPs. CONCLUSION: PEG-functionalized MNPs could be developed as a targeted drug delivery system and MRI contrast agent.

Development of Zoledronic Acid-Based Nanoassemblies for Bone-Targeted Anticancer Therapy.

Bone metastasis occurs in the majority of cancer patients, which hampers quality of life and significantly decreases survival. Aggressive chemotherapy is a traditional treatment regimen that induces severe systemic toxicities. Therefore, bone-directed therapies are highly warranted. We report a novel nanoparticle formulation that is composed of poly(vinylpyrrolidone) and tannic acid core nanoparticles (PVT NPs) that forms self-assembly with zoledronic acid (ZA@PVT NPs). The construction of ZA@PVT NPs was confirmed by particle size, zeta potential, transmission electron microscopy, and spectral analyses. An optimized bone-targeted ZA@PVT NPs formulation showed greater binding and internalization in in vitro with metastasis prostate and breast cancer cells. ZA@PVT NPs were able to deliver ZA more efficiently to tumor cells, which inhibited proliferation of human prostate and breast cancer cells. In addition, ZA@PVT NPs were capable of targeting mouse bones and prostate tumor microarray tissues (ex vivo) while sparing all other vital organs. More importantly, ZA@PVT NPs induce chemo sensitization to docetaxel treatment in cancer cells. Overall, the study results confirm that ZA-based, bone-targeted NPs have great potential for the treatment of bone metastasis in the near future.

Generation of engineered core-shell antibiotic nanoparticles.

Well-defined nanocomposite structures have received significant attention due to their superior combinatorial properties. Rational tuning of the core and shell of the nanostructure(s) can offer potent antibacterial activity. Such advanced core-shell nanocomposite methodologies allow not only the incorporation of antibacterial agents on the shell but also provide its stability and nurture antibacterial activity. Herein, antibiotic zinc oxide-curcumin (ZnO-Cum) core-shell nanoparticles for antibacterial application were synthesised. The ZnO-Cum core-shell nanoparticles were prepared by curcumin nanolayer deposition on zinc oxide nanoparticles via a sonication process. The resulting ZnO-Cum core-shell nanoparticles were spiracle in shape with a ∼45 nm ZnO core and ∼12 nm curcumin shell layer size, respectively, determined by transmission electron microscopy. X-ray diffraction analysis confirmed the formation of a core-shell crystal structure. Additionally, UV-DRS and ATR-FTIR spectral analysis support the existence of ZnO and curcumin in a core-shell nanocomposite. The antibacterial activities of nanoparticles developed were studied against Staphylococcus aureus and Streptococcus pneumoniae and Escherichia coli and Shigella dysenteriae bacterial stains using the diffusion method. A greater inhibition of the growth of Gram positive and negative bacteria was noticed upon treatment with core-shell ZnO and curcumin nanoparticles than the commercial antibiotic amoxicillin which indicates their antibacterial property. The findings of this study provide evidence that the zinc oxide-curcumin core-shell nanoparticles may be highly promising for antibacterial and biomedical applications.

Nano-hydroxyapatite polymeric hydrogels for dye removal.

Herein, two kinds of nano-hydroxyapatite were synthesized from Clam and Magellan shell by wet chemical precipitation method. Mainly, carboxymethyl cellulose/acrylamide/nano-hydroxyapatite composite hydrogels were developed via a free-radical polymerization process and investigated as a sorbent for Acid Blue 113 (AB) from aqueous AB solution. The swelled and kinetic behaviours of hydrogels were investigated using a gravimetric method. The swelling properties of the CMC-AM-hydrogels were influenced by the calcium electrolytes (Ca2+) content in nano-hydroxyapatites. The diffusion coefficient value increased with the increase of nano-hydroxyapatite content in the CMC-AM/nHA-CS (0.22353-0.27681 cm2 s-1) and CMC-AM/nHA-MS (0.22377-0.29737 cm2 s-1) hydrogels. The mechanism of water diffusion was found to be anomalous transport. The CMC-AM/nHA-MS hydrogels showed high AB absorption efficiency and adsorption capacities. These results explained that the nano-hydroxyapatites of Magellan shells based hydrogels are attractive nanocomposite hydrogels for the adsorption of dye in the water purification applications.

A versatile strategy to fabricate hydrogel-silver nanocomposites and investigation of their antimicrobial activity.

In this study, hydrogel-silver nanocomposites have been synthesized by a unique methodology, which involves formation of silver nanoparticles within swollen poly (acrylamide-co-acrylic acid) hydrogels. The formation of silver nanoparticles was confirmed by transmission electron microscopy (TEM) and surface plasmon resonance (SPR) which was obtained at 406 nm. The TEM of hydrogel-silver nanocomposites showed almost uniform distribution of nanoparticles throughout the gel networks. Most of the particles, as revealed from the particle-size distribution curve, were 24-30 nm in size. The X-ray diffraction pattern also confirmed the face centered cubic (fcc) structure of silver nanoparticles. The nanocomposites demonstrated excellent antibacterial effects on Escherichia coli (E. coli). The antibacterial activity depended on size of the nanocomposites, amount of silver nanoparticles, and amount of monomer acid present within the hydrogel-silver nanocomposites. It was also found that immersion of plain hydrogel in 20 mg/30 ml AgNO(3) solution yielded nanocomparticle-hydrogel composites with optimum bactericidal activity.

A mini review on hydrogels classification and recent developments in miscellaneous applications.

Hydrogels are composed of three-dimensional smart and/or hungry networks, which do not dissolve in water but swell considerably in an aqueous medium, demonstrating an extraordinary ability to absorb water into the reticulated structure. Such inherent feature is a subject of considerable scientific research interest which leads to a dominating path in extending their potential in hi-tech applications. Over the past decades, significant progress has been made in the field of hydrogels. Further, explorations are continuously being made in all directions at an accelerated pace for their extensive usage. In view of this, the present review discusses the subject on the miscellaneous hydrogels with regard to their raw materials, methods of fabrication and applications. In addition, this article summarizes the classification of hydrogels, based on their cross-linking and physical states. Lately, a brief outlook on the future prospects of hydrogels is also presented.

Disparity in rates of HPV infection and cervical cancer in underserved US populations.

There is a higher rate of HPV infection and cervical cancer incidence and mortality in underserved US population who reside in Appalachian mountain region compared to Northern Plains. Social and behavioral factors such as smoking and alcohol consumption are for such a high incidence. However, by and large, the reasons for these discrepancies lie in the reluctance of the underserved population to adopt preventive measures such as prophylactic Human papilloma virus (HPV) vaccines and Pap smear screening that have significantly reduced the incidence and mortality rate of cervical cancer in Caucasian women. Thus, it is clear that drastic change in social behavior and implementation of preventive measures is required to effectively reduce the incidence and mortality from cervical cancer in this underserved population.

Design of curcumin loaded cellulose nanoparticles for prostate cancer.

Prostate cancer (PC) is the most frequently diagnosed disease in men in the United States. Curcumin (CUR), a natural diphenol, has shown potent anti-cancer efficacy in various types of cancers. However, suboptimal pharmacokinetics and poor bioavailability limit its effective use in cancer therapeutics. Several successful CUR nanoformulations have recently been reported which improve upon these features; however, there is no personalized safe nanoformulation for prostate cancer. This study contributes two important scientific aspects of prostate cancer therapeutics. The first objective was to investigate the comparative cellular uptake and cytotoxicity evaluation of ß-cyclodextrin (CD), hydroxypropyl methylcellulose (cellulose), poly(lactic-co-glycolic acid) (PLGA), magnetic nanoparticles (MNP), and dendrimer based CUR nanoformulations in prostate cancer cells. Curcumin loaded cellulose nanoparticles (cellulose-CUR) formulation exhibited the highest cellular uptake and caused maximum ultrastructural changes related to apoptosis (presence of vacuoles) in prostate cancer cells. Secondly, the anti-cancer potential of the cellulose-CUR formulation was evaluated in cell culture models using cell proliferation, colony formation and apoptosis (7-AAD staining) assays. In these assays, the cellulose-CUR formulation showed improved anti-cancer efficacy compared to free curcumin. Our study shows, for the first time, the feasibility of cellulose-CUR formulation and its potential use in prostate cancer therapy.

Design and engineering of nanogels for cancer treatment.

Here, we provide a comprehensive insight into current advances in the use of nanogel-mediated chemotherapy for cancer treatment. Nanogels are composed of cross-linked three-dimensional polymer chain networks that are formed via covalent linkages or self-assembly processes. The porosity between the cross-linked networks of nanogels not only provides an ideal reservoir for loading drugs, oligonucleotides and imaging agents, but also protects them from environmental degradation and hazards. Here, we focus mainly on novel synthetic strategies and key considerations in the design of nanogel-based drug delivery systems for controlled and targeted cancer therapeutic applications.

Interaction of curcumin nanoformulations with human plasma proteins and erythrocytes.

BACKGROUND: Recent studies report curcumin nanoformulation(s) based on polylactic-co-glycolic acid (PLGA), ß-cyclodextrin, cellulose, nanogel, and dendrimers to have anticancer potential. However, no comparative data are currently available for the interaction of curcumin nanoformulations with blood proteins and erythrocytes. The objective of this study was to examine the interaction of curcumin nanoformulations with cancer cells, serum proteins, and human red blood cells, and to assess their potential application for in vivo preclinical and clinical studies. METHODS: The cellular uptake of curcumin nanoformulations was assessed by measuring curcumin levels in cancer cells using ultraviolet-visible spectrophotometry. Protein interaction studies were conducted using particle size analysis, zeta potential, and Western blot techniques. Curcumin nanoformulations were incubated with human red blood cells to evaluate their acute toxicity and hemocompatibility. RESULTS: Cellular uptake of curcumin nanoformulations by cancer cells demonstrated preferential uptake versus free curcumin. Particle sizes and zeta potentials of curucumin nanoformulations were varied after human serum albumin adsorption. A remarkable capacity of the dendrimer curcumin nanoformulation to bind to plasma protein was observed, while the other formulations showed minimal binding capacity. Dendrimer curcumin nanoformulations also showed higher toxicity to red blood cells compared with the other curcumin nanoformulations. CONCLUSION: PLGA and nanogel curcumin nanoformulations appear to be very compatible with erythrocytes and have low serum protein binding characteristics, which suggests that they may be suitable for application in the treatment of malignancy. These findings advance our understanding of the characteristics of curcumin nanoformulations, a necessary component in harnessing and implementing improved in vivo effects of curcumin.

Poly(ß-cyclodextrin)/curcumin self-assembly: a novel approach to improve curcumin delivery and its therapeutic efficacy in prostate cancer cells.

A novel PCD/CUR self-assembly approach for improved curcumin delivery to prostate cancer cells is described. The formation of PCD/CUR was confirmed using FTIR, DSC, TGA, and SEM/TEM, and their stability and solubility under physiological conditions was demonstrated. A mechanism for self-assembly is proposed. Intracellular uptake of the self-assemblies was studied by flow cytometry and immunofluorescence microscopy. The therapeutic efficacy was determined by cell proliferation and colony formation assays using C4-2, DU145 and PC3 prostate cancer cells. The results suggest that the PCD/CUR formulation could be a useful system for improving curcumin delivery and its therapeutic efficacy in prostate cancer.

beta-Cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells.

Curcumin, a hydrophobic polyphenolic compound derived from the rhizome of the herb Curcuma longa, possesses a wide range of biological applications including cancer therapy. However, its prominent application in cancer treatment is limited due to sub-optimal pharmacokinetics and poor bioavailability at the tumor site. In order to improve its hydrophilic and drug delivery characteristics, we have developed a beta-cyclodextrin (CD) mediated curcumin drug delivery system via encapsulation technique. Curcumin encapsulation into the CD cavity was achieved by inclusion complex mechanism. Curcumin encapsulation efficiency was improved by increasing the ratio of curcumin to CD. The formations of CD-curcumin complexes were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), scanning electron microscope (SEM), and transmission electron microscope (TEM) analyses. An optimized CD-curcumin complex (CD30) was evaluated for intracellular uptake and anti-cancer activity. Cell proliferation and clonogenic assays demonstrated that beta-cyclodextrin-curcumin self-assembly enhanced curcumin delivery and improved its therapeutic efficacy in prostate cancer cells compared to free curcumin.

Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells.

Curcumin, a natural polyphenolic compound, has shown promising chemopreventive and chemotherapeutic activities in cancer. Although phase I clinical trials have shown curcumin as a safe drug even at high doses, poor bioavailability and suboptimal pharmacokinetics largely moderated its anti-cancer activity in pre-clinical and clinical models. To improve its applicability in cancer therapy, we encapsulated curcumin in poly(lactic-co-glycolide) (PLGA) (biodegradable polymer) nanoparticles, in the presence of poly(vinyl alcohol) and poly(L-lysine) stabilizers, using a nano-precipitation technique. These curcumin nano-formulations were characterized for particle size, zeta potential, drug encapsulation, drug compatibility and drug release. Encapsulated curcumin existed in a highly dispersed state in the PLGA core of the nanoparticles and exhibited good solid-solid compatibility. An optimized curcumin nano-formulation (nano-CUR6) has demonstrated two and sixfold increases in the cellular uptake performed in cisplatin resistant A2780CP ovarian and metastatic MDA-MB-231 breast cancer cells, respectively, compared to free curcumin. In these cells, nano-CUR6 has shown an improved anti-cancer potential in cell proliferation and clonogenic assays compared to free curcumin. This effect was correlated with enhanced apoptosis induced by the nano-CUR6 formulation. Herein, we have also shown antibody conjugation compatibility of our PLGA-NP formulation. Results of this study suggest that therapeutic efficacy of curcumin may be enhanced by such PLGA nanoparticle formulations, and furthermore tumor specific targeted delivery of curcumin is made feasible by coupling of anti-cancer antibody to the NPs.

Fabrication, characterization of chitosan/nanosilver film and its potential antibacterial application.

In this work chitosan/silver nanoparticle films were synthesized by a simple photochemical method of reduction of silver ions in an acidic solution of AgNO(3) and chitosan. This is a novel, cheap, easy, quick and in situ approach to prepare chitosan films loaded with silver nanoparticles (AgNPs). Chitosan used here is a natural polymer and acts as a very good chelating and stabilizing agent; thus, this approach of formation of chitosan/silver nanoparticle films is proved to be an excellent 'green approach' for the synthesis of metal nanoparticle composites. The presence of silver nanoparticles was confirmed from the transmission electron microscopy (TEM), X-ray diffraction (XRD) and thermogravimetric analysis (TGA) of the film. The surface plasmon resonance (SPR) obtained at 400 nm also confirmed the presence of nanosilver in the chitosan film. The developed chitosan-nanosilver films demonstrated excellent antibacterial action against model bacteria, Escherichia coli and Bacillus. This approach can be easily used in the large-scale production of such silver-nanoparticles-loaded chitosan films. These films can be used as antimicrobial packaging materials, as wound dressings and can also be grafted onto various implants.