Naked Counterparts Research Articles

In vivo distribution characteristics and anti-tumor effects of doxorubicin encapsulated in PEG-modified niosomes in solid tumor-bearing mice

Niosomes, non-ionic surfactant-based vesicles, are capable of encapsulating various drugs, and surface modifications by polyethylene glycol (PEG) are expected to facilitate the passive targeting of encapsulated drugs to solid tumors due to the longer blood circulation time. However, the niosomalization of drugs may also enhance the delivery of drugs to specific tissues at which free drugs do not normally accumulate. Therefore, in the present study, we prepared several doxorubicin (DOX)-encapsulated niosomes composed of different non-ionic surfactants, and examined their in vitro stability, in vivo biodisposition, and anti-tumor effects in solid tumor-bearing mice. In vitro DOX release from Brij 72 niosomes and Span 20 niosomes in the presence of serum was significantly suppressed by their PEGylation. Moreover, the PEGylation of Brij 72 niosomes and Span 20 niosomes markedly increased the plasma level of DOX encapsulated in each niosome after their intravenous injection into tumor-bearing mice. The liver, spleen, and heart distributions of DOX encapsulated in PEG Brij 72 niosomes and Span 20 niosomes were markedly lower and their tumor dispositions were markedly larger than each naked counterpart. These two DOX-encapsulated PEG niosomes exerted strong anti-tumor effect and prolonged the survival time of tumor-bearing mice. On the other hand, PEGylation did not significantly affect the in vitro stability, in vivo biodisposition, or anti-tumor effects of Tween 60 niosomes. These results demonstrate that the PEGylation of Brij 72 and Span 20 niosomes improved the biodisposition of encapsulated anti-cancer drugs, thereby increasing their therapeutic efficacies.

Cell membrane-coated mesoporous silica nanorods overcome sequential drug delivery barriers against colorectal cancer

Local delivery of nanomedicines holds therapeutic promise for colorectal cancer (CRC). However, it presents tremendous challenges due to the existence of multiple physiological barriers, especially intracellular obstacles, including intracellular trafficking, subcellular accumulation, and drug release. Herein, we report a multifunctional nanoparticle (CMSNR) by wrapping the mesoporous silica nanorod with cell membrane derived from CRC cells for improved chemotherapy. Compared with their naked counterparts, the cell membrane endowed CMSNR with homotypic targeting and improved cellular uptake capacities. Due to the rod-like shape, CMSNR achieved superior colorectal mucus permeability, enhanced tumor accumulation, and boosted cellular uptake than their spherical counterparts. Moreover, the internalized CMSNR underwent robust intracellular trafficking and gained augmented motility toward the nucleus, leading to efficient perinuclear accumulation and a subsequent 5.6-fold higher nuclear accumulation of loaded drug than that of nanospheres. In the orthotopic colorectal tumor-bearing nude mice, rectally administrated mefuparib hydrochloride (MPH)-loaded CMSNR traversed the colorectal mucus, penetrated the tumor tissue, and successfully aggregated in the perinuclear region of cancer cells, thus exhibiting significantly improved antitumor outcomes. Our findings highlight the shape-based design of cell membrane-coated nanoparticles that can address sequential drug delivery barriers has a promising future in cancer nanomedicine.

Paclitaxel and Myrrh oil Combination Therapy for Enhancement of Cytotoxicity against Breast Cancer; QbD Approach

Paclitaxel (PX), plant alkaloid, is a chemotherapeutic agent intended for treating a wide variety of cancers. The objective of the present study was to formulate and evaluate the anticancer activity of PX loaded into a nanocarrier, mainly PEGylated nanoemulsion (NE) fabricated with myrrh essential oil. Myrrh essential oil has been estimated previously to show respectable anticancer activity. Surface modification of the formulation with PEG-DSPE would help in avoiding phagocytosis and prolong the residence time in blood circulation. Various NE formulations were developed after operating (22) factorial design, characterized for their particle size, in vitro release, and hemolytic activity. The optimized formula was selected and compared to its naked counterpart in respect to several characterizations. Quantitative amount of protein absorbed on the formulation surfaces and in vitro release with and without serum incubation were evaluated. Ultimately, MTT assay was conducted to distinguish the anti-proliferative activity. PEGylated PX-NE showed particle size 170 nm, viscosity 2.91 cP, in vitro release 57.5%, and hemolysis 3.44%, which were suitable for intravenous administration. A lower amount of serum protein adsorbed on PEGylated PX-NE surface (16.57 µg/µmol) compared to naked counterpart (45.73 µg/µmol). In vitro release from PEGylated NE following serum incubation was not greatly affected (63.3%), in contrast to the naked counterpart (78.8%). Eventually, anti-proliferative effect was obtained for PEGylated PX-NE achieving IC50 38.66 µg/mL. The results obtained recommend PEGylated NE of myrrh essential oil as a candidate nanocarrier for passive targeting of PX.

Significant of injectable brucine PEGylated niosomes in treatment of MDA cancer cells

Brucine (BRU) as a natural alkaloid has antitumor, anti-inflammatory and anti-proliferation activity However; its clinical application is limited due to its low water solubility. The aim of this study was to increase the therapeutic efficacy of BRU using PEGylated niosomal as nanocarrier. Here BRU loaded niosomes using different surfactants (Brij 52, Span 60 and Poloxamer 184) with and without PEG-DSPE were prepared. Niosomes were fabricated with particle size not exceeding 311 nm and entrapment ranged between 53 and 64%. Total serum protein adsorbed was ranged from 18.2 ± 3.7 up to 47.5 ± 3.2 μg/μl total lipids. In vitro drug release showed no significant difference for PEGylated niosomes over 24 h with and without serum incubation. In vitro cytotoxicity assay revealed that PEGylated niosome prepared with span 60 has considerable anti-cancer activity against MDA-MB-231 cell line comparable with blank niosome, free BRU and naked counterpart. Eventually, PEGylated niosomal formulation demonstrated the lowest tumor volume (732.42 mm3) and enhanced survival time (57 days). Based on the obtained results, loading the niosomes with BRU and coating them with PEG enhanced their efficacy and selectivity toward cancer cells, presenting a promising drug delivery system for targeting drug to cancer tissue.

Date Palm Extract (Phoenix dactylifera) PEGylated Nanoemulsion: Development, Optimization and Cytotoxicity Evaluation.

Date palm fruit (Phoenix dactylifera) is reputed to have numerous biological activities, including anticancer properties. To utilize the great fortune of this fruit, the current study aimed to maximize its pharmacological activity. Date palm extract (DPE) of Khalas cultivar was obtained in powder form and then was formulated into nanoemulsion (NE). The optimized DPE-NE was formulated along with its naked counterpart followed by studying their physical and chemical properties. A qualitative assessment of total serum protein associated with the surface of formulations was implemented. Studies for the in vitro release of DPE from developed NE before and after incubation with serum were investigated. Eventually, an MTT assay was conducted. Total phenolic and flavonoid contents were 22.89 ± 0.013 mg GAE/g of dry DPE and 9.90 ± 0.03 mg QE/g of dry DPE, respectively. Homogenous NE formulations were attained with appropriate particle size and viscosity that could be administered intravenously. The optimized PEGylated NE exhibited a proper particle size, PDI, and zeta potential. Total serum protein adsorbed on PEG-NE surface was significantly low. The release of the drug through in vitro study was effectively extended for 24 h. Ultimately; PEGylated NE of DPE attained significant inhibition for cancer cell viability with IC50 values of 18.6 ± 2.4 and 13.5 ± 1.8 µg/mL for MCF-7 and HepG2 cell lines, respectively. PEGylated NE of DPE of Khalas cultivar will open the gate for future adjuvants for cancer therapy.

Viral Envelope Membrane: A Special Entry Pathway and a Promising Drug Target.

Enveloped viruses belong to a large class of pathogens responsible for multiple serious diseases. Their spread into new territories has been the cause of major epidemics throughout human history, including the Spanish flu in 1918 and the latest COVID-19 pandemic. Thanks to their outer membrane, consisting essentially of host lipids, enveloped viruses are more resistant to enzymes and are also less susceptible to host immune defenses than their naked counterparts. Therefore, the development of effective approaches to combat enveloped virus infections represents a major challenge for antiviral therapy in the current century. This review focuses on the characteristics of enveloped viruses, their importance in the entry phase, drugs targeting envelope membrane- mediated entry, and those specifically designed to target the envelope. The broad- -spectrum antiviral activity of these compounds can be attributed to their ability to affect the envelope, an essential structural feature common to several viruses. This makes this class of compounds agents of great interest when no specific drugs or vaccines are available to block viral infections.

Microengineered biosynthesized cellulose as anti-fibrotic in vivo protection for cardiac implantable electronic devices

Upon cardiac implantable electronic device (CIED) exchange, upgrade, or revision surgery patients are exposed to a considerable risk of adverse events. The presence of firm fibrotic tissue endangers these procedures. Leads can be damaged in the attempt of freeing them from fibrotic tissue. Hematoma can form as result of capsulectomy, pocket debridement and leads dissection. Due to the increasing number of CIED exchange, upgrade and revision surgeries, the incidence of related complications is expected to rise in the near future.The aim of the study was to evaluate the feasibility, safety, and performance of a rationally micro-engineered non-resorbable biosynthesized cellulose (BC) membrane as conformal wrapping protection around CIED implants. Protective membranes were generated by means of a recently established method to transfer on-demand microscale geometries onto the surface of BC. A chronic minipig animal model was selected to investigate the performance of the BC anti-fibrotic protection, directly measured as reduction of fibrotic tissue formation. Sixteen (n = 16) animals received each one BC coated pacemaker (PMC) and one native pacemaker (BI) at equivalent anatomical sites. BC protective layers were juxtaposed around pacemakers through a fast and well-repeatable procedure. Explants were performed at 3 and 12 months after implantation. Endpoint analysis showed that the BC protective layers were 100% integer, with no sign of chemical or mechanical degradation and appeared as a thin layer of white-tan material, adherent to the surrounding thin fibrous capsule, from which it could be peeled off by gently pulling with forceps. The protective effect of micro-engineered BC yielded an average thickness reduction of 66% of the fibrotic tissue thickness generated around PMC, as compared to that measured around the naked counterpart (i.e. the BI). When protected by in BC, both the generator and the proximal parts of the leads were completely free from fibrotic tissue. The insertion of an anti-adhesive, non-resorbable and well-tolerated BC interface between the implant and the surrounding tissue in the surgical pocket significantly reduced the formation of fibrotic tissue, ensuring an easy access to the device pocket, and thus creating the conditions for simplified CIED revision surgeries.

Active Surface Hydrophobicity Switching and Dynamic Interfacial Trapping of Microbial Cells by Metal Nanoparticles for Preconcentration and In-Plane Optical Detection.

The surface hydrophobicity of a microbial cell is known to be one of the important factors in its adhesion to an interface. To date, such property has been altered by either genetic modification or external pH, temperature, and nutrient control. Here we report a new strategy to engineer a microbial cell surface and discover the unique dynamic trapping of hydrophilic cells at an air/water interface via hydrophobicity switching. We demonstrate the surface transformation and hydrophobicity switching of Escherichia coli (E. coli) by metal nanoparticles. By employing real-time dark-field imaging, we directly observe that hydrophobic gold nanoparticle-coated E. coli, unlike its naked counterpart, is irreversibly trapped at the air/water interface because of elevated hydrophobicity. We show that our surface transformation method and resulting dynamic interfacial trapping can be generally extended to Gram-positive bateria, Gram-negative bacteria, and fungi. As the dynamic interfacial trapping allows the preconcentration of microbial cells, high intensity of scattering light, in-plane focusing, and near-field enhancement, we are able to directly quantify E. coli as low as 1.0 × 103 cells/ml by using a smartphone with an image analyzer. We also establish the identification of different microbial cells by the characteristic Raman transitions directly measured from the interfacially trapped cells.

Sweetness Reduces Cytotoxicity and Enables Faster Cellular Uptake of Sub-30 nm Amphiphilic Nanoparticles.

Glycoconjugates are versatile entities used for the manufacturing of targeted drug delivery nanocontainers because of their outstanding capability to bind to lectins, which are proteins that can be found overexpressed in the membranes of unhealthy cells. The assisted attachment to pathological cells can further enable a more efficient intracellular delivery of loaded active agents, thereby reducing side effects that commonly compromise chemotherapies. In this framework, azide-terminated polyethylene oxide (PEO) chains coupled to a 22-carbon chain were synthesized (azide-PEO900-docosanoate). The resulting amphiphile was further functionalized by introducing different sugar moieties to the PEO chains via the click chemistry approach. Sub-30 nm, negatively charged, and spherical nanoparticles were prepared in water by self-assembly of the synthesized molecules using the straightforward nanoprecipitation protocol. The produced entities do not induce hemolysis in red blood cells at c ≤ 200 μg mL-1, and they are not cytotoxic to healthy cells [telomerase immortalized rhesus fibroblasts (Telo-RF)] at c ≤ 50 μg mL-1. The sugar-decorated nanoparticles are less cytotoxic compared with their naked counterparts at the concentration range assessed. The kinetics of cellular uptake of both entities into normal (Telo-RF) and tumor (HeLa) cells were monitored via fluorescence microscopy and flow cytometry. The nanoparticles are internalized faster in cancer cells than in normal cells, regardless of functionalization. Moreover, the functionalized nanoparticles are internalized faster in HeLa cells, while the reverse was observed in healthy Telo-RF cells. The distinct surface characteristics of the assemblies create an opportunity to expedite the uptake of nanoparticles particularly by tumor cells, and this accordingly can lead to a more effective intracellular delivery of therapeutic molecules loaded into nanoparticle's reservoirs.

Highly Luminescent Encapsulated Narrow Bandgap Polymers Based on Diketopyrrolopyrrole.

We present the synthesis and characterization of a series of encapsulated diketopyrrolopyrrole red-emitting conjugated polymers. The novel materials display extremely high fluorescence quantum yields in both solution (>70%) and thin film (>20%). Both the absorption and emission spectra show clearer, more defined features compared to their naked counterparts demonstrating the suppression of inter and intramolecular aggregation. We find that the encapsulation results in decreased energetic disorder and a dramatic increase in backbone colinearity as evidenced by scanning tunnelling microscopy. This study paves the way for diketopyrrolopyrrole to be used in emissive solid state applications and demonstrates a novel method to reduce structural disorder in conjugated polymers.

Preparation of Phytic Acid/Silane Hybrid Coating on Magnesium Alloy and Its Corrosion Resistance in Simulated Body Fluid

In order to decrease the corrosion rate and improve the bioactivity of magnesium alloy, phytic acid/saline hybrid coatings were synthesized on AZ31 magnesium alloys by sol–gel dip-coating method. It was found that the mole ratio of phytic acid to γ-APS had a great influence on coating morphology and the corresponding corrosion resistance of the coated magnesium alloys. When the mole ratio of phytic acid to γ-APS was 1:1, the obtained hybrid coating was integral and without cracks, which was ascribed to the strong chelate capability of phytic acid and Si-O-Si network derived from silane. Electrochemical test result indicated that the corrosion resistance of the coated magnesium alloy was about 27 times larger than that of the naked counterpart. In parallel, immersion test showed that the phytic acid/silane hybrid coating could induce CaP-mineralized product deposition, which offered another protection for magnesium alloy.

Spitzer observations of large amplitude variables in the LMC and IC 1613

The 3.6 and 4.5 micron characteristics of AGB variables in the LMC and IC1613 are discussed. For C-rich Mira variables there is a very clear period-luminosity-colour relation, where the [3.6]-[4.5] colour is associated with the amount of circumstellar material and correlated with the pulsation amplitude. The [4.5] period-luminosity relation for dusty stars is approximately one mag brighter than for their naked counterparts with comparable periods.

Microwave aqueous synthesis of hydroxyapatite bilayer coating on magnesium alloy for orthopedic application

Magnesium and magnesium alloys as promising biodegradable implants gain increasing interest. To improve their corrosion resistance and cytocompatibility, hydroxyapatite (HA) coatings with double-layer structure were synthesized on magnesium alloy through a rapid microwave aqueous chemical route. The coating prepared with microwave heating time of 10min consisted of cotton-like HA as the surface layer and strip-like HA as the bottom layer, and the coating thickness was ∼10.0μm. The growth kinetic, electrochemical property, degradation, mineralization and cytocompatibility of HA coated and naked magnesium alloys were investigated. Potentiodynamic polarization test demonstrated that corrosion current density of HA coated magnesium alloy prepared with microwave heating time of 10min was ∼100 times lower than that of the naked counterpart. Immersion test indicated that the strip-like HA layer with thickness of ∼7.7μm and low solubility endowed magnesium alloy with initial-stage protection; the nano-scale cotton-like HA layer exhibited high HA mineralization capacity. The mineralized layer reached ∼12.7μm in thickness after 24days’ immersion, eventually integrated with the original HA bilayer coating, providing favorable long-term protection for magnesium alloy. Moreover, HA coated magnesium alloy prepared with microwave heating time of 10min enhanced osteoblast proliferation than the naked counterpart. These attractive results indicated that this HA bilayer coating is a potential protective coating on biodegradable magnesium and magnesium alloys for orthopedic application.

Nanocarrier mediated delivery of siRNA/miRNA in combination with chemotherapeutic agents for cancer therapy: current progress and advances.

Chemotherapeutic agents have certain limitations when it comes to treating cancer, the most important being severe side effects along with multidrug resistance developed against them. Tumor cells exhibit drug resistance due to activation of various cellular level processes viz. activation of drug efflux pumps, anti-apoptotic defense mechanisms, etc. Currently, RNA interference (RNAi) based therapeutic approaches are under vibrant scrutinization to seek cancer cure. Especially small interfering RNA (siRNA) and micro RNA (miRNA), are able to knock down the carcinogenic genes by targeting the mRNA expression, which underlies the uniqueness of this therapeutic approach. Recent research focus in the regime of cancer therapy involves the engagement of targeted delivery of siRNA/miRNA in combinations with other therapeutic agents (such as gene, DNA or chemotherapeutic drug) for targeting permeability glycoprotein (P-gp), multidrug resistant protein 1 (MRP-1), B-cell lymphoma (BCL-2) and other targets that are mainly responsible for resistance in cancer therapy. RNAi-chemotherapeutic drug combinations have also been found to be effective against different molecular targets as well and can increase the sensitization of cancer cells to therapy several folds. However, due to stability issues associated with siRNA/miRNA suitable protective carrier is needed and nanotechnology based approaches have been widely explored to overcome these drawbacks. Furthermore, it has been univocally advocated that the co-delivery of siRNA/miRNA with other chemodrugs significantly enhances their capability to overcome cancer resistance compared to naked counterparts. The objective of this article is to review recent nanocarrier based approaches adopted for the delivery of siRNA/miRNA combinations with other anticancer agents (siRNA/miRNA/pDNA/chemodrugs) to treat cancer.

Naked Viruses That Aren't Always Naked: Quasi-Enveloped Agents of Acute Hepatitis.

Historically, viruses were considered to be either enveloped or nonenveloped. However, recent work on hepatitis A virus and hepatitis E virus challenges this long-held tenet. Whereas these human pathogens are shed in feces as naked nonenveloped virions, recent studies indicate that both circulate in the blood completely masked in membranes during acute infection. These membrane-wrapped virions are as infectious as their naked counterparts, although they do not express a virally encoded protein on their surface, thus distinguishing them from conventional enveloped viruses. The absence of a viral fusion protein implies that these quasi-enveloped virions have unique mechanisms for entry into cells. Like true enveloped viruses, however, these phylogenetically distinct viruses usurp components of the host ESCRT system to hijack host cell membranes and noncytolytically exit infected cells. The membrane protects these viruses from neutralizing antibodies, facilitating dissemination within the host, whereas nonenveloped virions shed in feces are stable in the environment, allowing for epidemic transmission.

The shape effect of PEGylated mesoporous silica nanoparticles on cellular uptake pathway in Hela cells

The shape of nanoparticles plays an important role in the interaction between cells and particles. However, the shape effect of mesoporous silica nanoparticles on the cellular uptake pathway and mechanism has not been reported. Herein, three different kinds of fluorescent mesoporous silica nanoparticles (FMSN, aspect ratio=1, 2, and 4, ca. 100nm in diameter) with similar fluorescent intensity at equivalent concentration were fabricated by a co-condensation strategy. In simulated body fluid (SBF), the PEGylated FMSN (FMSN-PEG) have higher dispersity and stability than the naked counterparts. So we chose the FMSN-PEG to research of shape effect on the cellular uptake pathway in Hela cells. We found that the uptake kinetics and pathway of three different shaped FMSN-PEG were obviously shape-dependent. The long-rod FMSN-PEG (NLR-PEG) showed higher intracellular retention amount than the short-rod FMSN-PEG (NSR-PEG) and the sphere FMSN-PEG (NS-PEG) almost over 8h. The NSR-PEG showed the lowest intracellular amount especially with prolonged incubation time. We also found that the cellular entry pathway of NS-PEG, NSR-PEG, and NLR-PEG into Hela cells was regulated by particle shape. Spherical particles preferred to be internalized via the clathrin-mediated pathway, whereas MSN with larger aspect ratios (ARs) favored to be internalized via caveolae-mediated pathway, which could explain their different uptake kinetics. Our findings may provide useful information for optimizing the nano-based drug delivery and bio-imaging systems.

Electronic and magnetic properties of organometallic clusters: From the molecular to the metallic state

We have performed a linear combination of Gaussian-type orbitals, LCGTO, local density functional, LDF, calculations on a series of low- and high-nuclearity carbonylated Ni clusters and on their naked counterparts. We have found that while the bare Ni clusters do exhibit several features in common with the bulk metal, the low-nuclearity carbonylated clusters do not show any metallic behavior. Signs of a developing metallic character are found for high-nuclearity Ni cluster carbonyls where it is possible to distinguish between “surface” atoms, which are directly interacting with the ligand sphere, and “bulk” atoms, which are only interacting with other metal atoms. Through the analysis of the magnetic properties of these systems it is possible to formulate a general model which rationalizes both the metallic behavior of the free Ni clusters and the nonmetallic behavior in certain carbonylated Ni clusters. This model is based on the perturbations induced by the ligands on the electronic structure of the metal atoms in the cluster. © 1992 John Wiley & Sons, Inc.