Search

In 2023, the world is facing problems such as global warming, hazardous chemicals, non-destructible plasticizers, similar to viruses. All of these issues are major concerns for our environment. To address these issues, there is a strong need for a multifunctional material that serves as a catalyst, which is stable, efficient, selective, and reusable. The conventional catalyst based on photoinduced charge carriers is insufficient. The intrinsic properties of a material, such as ferroelectricity, piezoelectricity, and magnetism, can play a role in the catalysis process and enhance the catalyst's activity by driving forces such as spontaneous polarization, piezoelectric coefficient, and ferromagnetism at room temperature. These qualities are found and cherished in the classic ceramic semiconductor Bismuth Ferrite (BiFeO3; BFO), commonly known as the "The drosophila of multiferroics." BFO exhibits ferroic orderings at room temperature. For catalytic purposes, a large surface area is required to have a high number of active sites. Therefore, nanosized BFO particles are chosen. Although BFO nanoparticles (NPs) absorb visible light, they have smaller ferroelectric polarization than bulk BFO due to reduced crystal asymmetry, and they also possess weak ferromagnetic properties. To achieve a larger surface area while maintaining increased ferroelectric and magnetic properties, ionic engineering at Bi and Fe sites is utilized. The dopants not only further reduce the particle size of BFO NPs but also influence the shape of NPs, resulting in different morphologies. The macroscopic and local crystal structure of doped BFO NPs is examined using several techniques. The alteration in Bi-O and Fe-O bond parameters and the increase in microstrain of the BFO crystal structure due to doping are major factors responsible for altered ferroic properties. Doping magnetic ions at the Fe site of BFO NPs leads to an increase in total magnetization mainly through superexchange interaction, disrupting the spin cycloid. Further co-doping at the Bi site results in even higher magnetization due to changes in the Fe-O-Fe bond angle and the presence of uncompensated spins on the surface of small-sized NPs. Doping also influences the coercive field and anisotropy of the NPs, making them suitable for magnetic hyperthermia. Doped BFO NPs exhibit efficiency in converting magnetic energy into heat when exposed to an alternating magnetic field, showing promise for applications in magnetic hyperthermia for cancer treatment. The local ferroelectricity and piezoelectric response in doped BFO NPs are found to be higher than in pristine BFO NPs due to crystal structure distortion caused by asymmetrical Bi-O bonds in the BiO12 cuboctahedron and resulting alterations in the FeO6 octahedron. Doping Mn at the Fe site does not significantly influence the ferroelectricity of BFO NPs. However, further doping of divalent cations (Ca2+ or Ba2+) at the Bi site in BiFe0.95Mn0.05O3 (BFM) NPs reduces the local ferroelectricity, while doping of trivalent (Dy3+) and monovalent (Ag+) cations into BFM NPs increases the ferroelectric properties of BFM NPs approximately three times. This study finds that single doping at the Fe site has a substantial influence on the band gap compared to doping at the Bi site, primarily due to the indirect effect on the electronic structure of BFO NPs. The band gap of BFO, which is 2.2 eV, can be reduced to 1.6 eV with the appropriate ratio of Ba and Mn co-doping. This provides the maximum utilization of the solar spectrum to generate photoinduced charge carriers for catalytic purposes. Dopants at the Bi site have a slight impact on the light absorption properties of the BFO NPs, creating oxygen vacancies or defect states in the band gap. The catalytic activity of the doped BFO NPs for the degradation of organic pollutants under visible and UV light illumination is compared. Ba-doped BFM NPs exhibit enhanced photocatalytic efficiency compared to pristine BFM and BFO NPs. 1 mol% Ba-doped BFM NPs degrade rhodamine B and methyl orange dyes within 60 and 25 minutes under UV and visible illumination, respectively. The increased photocatalytic efficiency in Ba-doped BFM NPs is attributed to a cooperative effect of factors such as increased light absorption ability, large surface area, active surface, reduced recombination of charge carriers, and spontaneous polarization to mitigate photoinduced charge carrier recombination. In piezo-photocatalysis, Dy-BFM and Ag-BFM NPs show the best photocatalytic activity under ultrasonication conditions. The increase in spontaneous polarization by mono- and trivalent doping is one of the major factors in enhancing the photocatalytic performance, along with stronger light absorption in the visible range, low recombination rate of charge carriers, and larger surface area of NPs. Dibutyl phthalate (DBP) is notorious as an endocrine disruptor, making it a significant threat to both human health and the environment. Successful photodegradation of DBP is achieved under UV light irradiation within 2.5 hours using Ag-doped BFM NPs supported on graphene oxide (GO) nanosheets. Gas chromatography and mass spectrometry (GCMS) show that Ag-BFM NPs supported on GO have a higher photodegradation efficiency than the pristine free-standing BFO NPs alone. The photodegradation process of DBP generates various intermediate products, such as phthalic acid, benzoic acid, benzaldehyde, and 3-methyl butyric acid, before achieving complete mineralization into carbon dioxide and water. The investigation delves into the functionality exhibited by doped BFM NPs concerning the hydrogen evolution reaction (HER). The electrocatalytic activity of BFM NPs undergoes a transformative shift as a consequence of mono-, di-, and trivalent cation substitutions. Notably, strategic engineering of doping at the Bi site within BFM NPs yields a remarkable outcome, namely the reduction of the kinetic overpotential prerequisite for HER. This diminished overpotential in doped BFM NPs arises from the confluence of multifarious factors: diminished charge transfer resistance, augmented specific surface area, a discernible distribution of pore sizes ranging from narrow to broad, particles endowed with a shape boasting abundant active facets, and the integration of dopants as novel active sites upon the surface. Furthermore, the presence of surface defects, oxygen vacancies, and amplified microstrain within doped BFM NPs contributes to the reduced overpotential. This study underscores the successful synthesis of phase-pure doped and undoped BFO NPs with diverse morphologies using different methods and the profound impact of doping on their magnetic, electrical, optical, and catalytic properties. The findings highlight the tremendous multifunctional potential of doped BFO NPs in a wide range of applications. These doped BFM NPs encapsulate immense potential to revolutionize the realm of HER in the photoelectrochemical domain, owing to their profound light absorption capabilities and aptitude for catalysis. Dissertation, Universität Duisburg-Essen, 2023

In the recent years, herbal medicines have gained worldwide attention of peoples and researchers due to their esthetic value, more patient’s compliance and prominent therapeutic effects. Novel drug delivery systems for delivery of herbal drugs possesses several advantages over conventional formulations. It includes enhancement of solubility, bioavailability, and protection from toxicity, etc. The herbal drugs can be used in a more upright course with enhanced efficacy by incorporating them into suitable dosage forms. This can be achieved by designing novel drug delivery systems for such drugs. Such systems are polymeric nanoparticles, nanocapsules, phytosomes, animations, microsphere, etc. The present article highlights the current condition of the development of novel herbal formulations and summarizes their type of active components, biological activity, and applications of novel formulations.

The ferroelectricity of multivalent codoped Bismuth ferrite (BiFeO3; BFO) nanoparticles (NPs) is revealed and utilized for photocatalysis, exploiting their narrow electronic bandgap. The photocatalytic activity of ferroelectric photocatalysts BiFe0.95Mn0.05O3 (BFM) NPs and mono‐, di‐, or tri‐valent cations (Ag+, Ca2+, Dy3+; MDT) coincorporated BFM NPs are studied under ultrasonication and in acidic conditions. It is found that such doping enhances the photocatalytic activity of the ferroelectric NPs approximately three times. The correlation of the photocatalytic activity with structural, optical, and electrical properties of the doped NPs is established. The increase of spontaneous polarization by the mono‐ and tri‐valent doping is one of the major factors in enhancing the photocatalytic performance along with other factors such as stronger light absorption in the visible range, low recombination rate of charge carriers, and larger surface area of NPs. A‐site doping of BFO NPs by divalent elements suppresses the polarization, whereas trivalent (Dy3+) and monovalent (Ag+) cations provide an increase of polarization. The depolarization field in these single domain NPs acts as a driving force to mitigate recombination of the photoinduced charge carriers., The ferroelectricity of Ag/Ca/Dy‐doped BiFe0.95Mn0.05O3 nanoparticles are utilized for photocatalysis under ultrasonic conditions. The mitigated recombination of photoinduced charge‐carriers in the nanoparticles due to the depolarization field, is one of the important factors for the photocatalytic rate. The piezoresponse becomes a crucial parameter under ultrasonic conditions for ferroelectric photocatalysts. The pink dye (rhodamine B) is photodegraded using MDT doped nanoparticles. The ease of photoinduced charge carrier separation in single domain nanoparticles using the depolarization field as a driving force is shown. image

The present study aimed to investigate the brain targeting efficacy of Lamotrigine (LTG) loaded PLGA nanoparticles (LTG-PNPs) upon intranasal administration. LTG-PNPs were fabricated through the emulsification-solvent evaporation technique and evaluated for % Entrapment efficiency, particle size, in-vitro release, surface morphology, crystallinity, ex-vivo permeation & thermal behaviour. Biodistribution, gamma scintigraphy, and pharmacodynamic studies were performed in BALB/c mice, New Zealand rabbits, and Wistar rats respectively. LTG-PNPs exhibited % EE 71%; particle size 170.0 nm; Polydispersity index 0.191; zeta potential -16.60 mV. LTG-PNPs exhibited a biphasic release pattern. Biodistribution and gamma scintigraphy studies proved a greater amount of LTG in the brain following intranasal delivery of LTG-PNPs in comparison to LTG-SOL. Pharmacodynamic studies demonstrated delayed seizure onset time with LTG-PNPs in comparison to LTG-SOL. Intranasal administration of LTG-PNPs provided prolonged release, higher bioavailability, and better brain targeting bypassing the BBB. The developed formulation could be administered as a once-a-day formulation that would reduce the dosing frequency; dose; dose-related side effects; cost of the therapy and would be beneficial in the management of epilepsy as compared to the LTG-SOL. However, the proof of concept generated through these studies needs to be further validated in higher animals and human volunteers.

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.

In recent years scientific community has drawn a great deal of attention towards understanding the enigma of cluster of differentiation-44 (CD44) in order to deliver therapeutic agents more selectively towards tumor tissues. Moreover, its over-expression in variety of solid tumors has attracted drug delivery researchers to target this receptor with nanomedicines. Conventional nanomedicines based on biodegradable polymers such as poly(lactide-co-glycolide) (PLGA) are often associated with insufficient cellular uptake by cancer cells, due to lack of active targeting moiety on their surface. Therefore, to address this limitation, CD44 targeted PLGA nanomedicines has gained considerable interest for enhancing the efficacy of chemotherapeutic agents. In this review, we have elaborately discussed the recent progress in the design and synthesis of CD44 targeted PLGA nanomedicines used to improve tumor-targeted drug delivery. We have also discussed strategies based on co-targeting of CD44 with other targeting moieties such as folic acid, human epidermal growth factor 2 (HER2), monoclonal antibodies using PLGA based nanomedicines.

Spoilage of food by mycotoxigenic fungi poses a serious risk to food security throughout the world. In view of the negative effects of synthetic preservatives, essential oils (EOs) and their bioactive constituents are gaining momentum as suitable substitute to ensure food safety by controlling mycotoxins. However, despite their proven preservative potential against mycotoxins, the use of EOs/bioactive constituents in real food system is still restricted due to instability caused by abiotic factors and negative impact on organoleptic attributes after direct application. Nanoencapsulation in this regard could be a promising approach to address these problems, since the process can increase the stability of EOs/bioactive constituents, barricades their loss and considerably prevent their interaction with food matrices, thus preserving their original organoleptic qualities. The aim of this review is to provide wider and up-to-date overview on recent advances in nanoencapsulation of EOs/bioactive constituents with the objective to control mycotoxin contamination in food system. Further, the information on polymer characteristics, nanoencapsulation techniques, factors affecting the nanoencapsulation, applications of nanoencapsulated formulations, and characterization along with the study on their release kinetics and impacts on organoleptic attributes of food are discussed. Finally, the safety aspects of nanoencapsulated formulations for their safe utilization are also explored.

Nanostructured lipid carriers (NLC) have become a promising drug delivery system for topical delivery of drugs. Delivery of lipophilic drugs with improved stability and entrapment efficiency is one of the foremost benefits of NLC based formulations. The objective of the present study was to improve the permeation of poorly soluble curcumin into topical skin layers for the treatment of chronic inflammatory disorder psoriasis and microbial mediated acne vulgaris. Hot emulsification followed by probe sonication method was employed for the preparation of the curcumin loaded NLC. Further, in-vitro and ex-vivo characterization was performed for designed NLC. The designed NLC showed a mean particle size 96.2 ± 0.9 nm, entrapment efficiency of 70.5 ± 1.65% and zeta potential of -15.2 ± 0.566 mV. Curcumin-NLC showed extended in-vitro release upto 48 hours, whereas free curcumin showed 100% drug release within 4 hours. Ex-vivo skin permeation studies revealed 3.24 fold improved permeation and skin retention in the case of curcumin loaded NLC gel compared to free curcumin gel. The cell viability studies demonstrated the formulation components showed no toxicity towards keratinocyte cells. In keratinocyte cells, improved cell uptake was observed for curcumin-NLC compared to free curcumin dispersion. The results suggested that the NLC based formulation had potential to improve the efficacy of curcumin.

Mechanical strength of polymeric scaffolds deteriorates quickly in the physiological mileu. This can be minimized by reinforcing the polymeric matrix with graphene, a planar two-dimensional material with unique physicochemical and biological properties. Association between the sheet and polymer chains offers a range of porosity commensurate with tissue requirements. Besides, studies suggest that corrugated structure of graphene offers desirable bio-mechanical cues for tissue regeneration. This review covers three important aspects of graphene-polymer composites, (a) the opportunity on reinforcing the polymer matrix with graphene, (b) challenges associated with limited aqueous processability of graphene, and (c) physiological signaling in the presence of graphene. Among numerous graphene materials, our discussion is limited to graphene oxide (GO) and reduced graphene oxide (rGO) nanosheets. Challenges associated with limited dispersity of hydrophobic sheets within the polymeric matrix have been discussed at molecular level.

Наночастинки (НЧ) благородних металів знайшли своє потенційне застосування завдяки своїм фізичним, хімічним та біологічним властивостям порівняно з сипучими матеріалами. У цій роботі НЧ колоїдного срібла (Ag) готують методом хімічного відновлення, а різні дослідження представлені за допомогою УФ-спектроскопії, флуоресцентної (FL) спектроскопії, аналізатора динамічного розсіювання світла (DLS), інфрачервоної спектроскопії з перетворенням Фур'є (FTIR) та енергетично-дисперсійного рентгенівського (EDX) спектрометру. Спектр пропускання (УФ) показав наявність НЧ Ag в нижній спектральній області, а дослідження FL виявило пік випромінювання колоїдних НЧ Ag на довжинах хвиль 360 нм і 645 нм при довжині хвилі збудження 320 нм. Спектр FTIR схвалив різні функціональні групи, пов'язані з елементами, присутніми у вибірці. Середній діаметр НЧ Ag становить 58 нм за розрахунком методом DLS. EDX-спектри підтвердили піки елементів, що підтверджують утворення НЧ Ag. Крім того, НЧ Ag використовуються при виробництві сонячних батарей, чутливих до барвника (DSSC). Noble metal nanoparticles (NPs) are found their potential applications due to their physical, chemical and biological properties as compared to the bulk materials. In this work, colloidal silver (Ag) NPs are prepared by chemical reduction method and various investigations are presented using UV-vis spectroscopy, fluorescence (FL) spectroscopy, dynamic light scattering (DLS) particle size analyzer, Fourier transform infrared (FTIR) spectroscopy and energy dispersive X-ray (EDX) spectrometer. The transmittance spectrum (UV) showed the presence of Ag NPs at the lower spectral region, and FL study revealed the emission peak of colloidal Ag NPs at wavelengths of 360 nm and 645 nm with the excitation wavelength of 320 nm. FTIR spectrum endorsed the various functional groups related to the elements present in the sample. The average diameter of the Ag NPs is 58 nm as estimated by DLS technique. EDX spectra confirmed the peaks of elements confirming the formation of Ag NPs. Further, Ag NPs are used in the dye-sensitized solar cell (DSSC) fabrication and result is explored.

Rechargeable magnesium batteries are appealing as safe, low-cost systems with high-energy-density storage that employ predominantly dendrite-free magnesium metal as the anode. While significant progress has been achieved with magnesium electrolytes in recent years, the further development of Mg-ion batteries, however, is inherently limited by the lack of suitable cathode materials, mainly due to the slow diffusion of high-charge-density Mg-ions in the intercalation-type host structures and kinetic limitations of conversion-type cathodes that often causes poor cyclic stability. Nanostructuring the cathode materials offers an effective means of mitigating these challenges, due to the reduced diffusion length and higher surface areas. In this context, we present the highly reversible insertion of Mg-ions into nanostructured conversion-type CuS cathode, delivering high capacities of 300 mAh g−1 at room temperature and high cyclic stability over 200 cycles at a current density of 0.1 A g−1 with a high coulombic efficiency of 99.9%. These materials clearly outperform bulk CuS, which is electrochemically active only at an elevated temperature of 50 °C. Our results not only point to the important role of nanomaterials in the enhancement of the kinetics of conversion reactions but also suggest that nanostructuring should be used as an integral tool in the exploration of new cathodes for multivalent, i.e., (Mg, Ca, Al)-ion batteries.

Advances in the use of nanoparticles (NPs) has created promising progress in biotechnology and consumer-care based industry. This has created an increasing need for testing their safety and toxicity profiles. Hence, efforts to understand the cellular responses towards nanomaterials are needed. However, current methods using animal and cancer-derived cell lines raise questions on physiological relevance. In this aspect, in the current study, we investigated the use of pluripotent human embryonic stem cell- (hESCs) derived fibroblasts (hESC-Fib) as a closer representative of the in vivo response as well as to encourage the 3Rs (replacement, reduction and refinement) concept for evaluating the cytotoxic and genotoxic effects of zinc oxide (ZnO), titanium dioxide (TiO2) and silicon-dioxide (SiO2) NPs. Cytotoxicity assays demonstrated that the adverse effects of respective NPs were observed in hESC-Fib beyond concentrations of 200 &micro, g/mL (SiO2 NPs), 30 &micro, g/mL (TiO2 NPs) and 20 &micro, g/mL (ZnO NPs). Flow cytometry results correlated with increased apoptosis upon increase in NP concentration. Subsequently, scratch wound assays showed ZnO (10 &micro, g/mL) and TiO2 (20 &micro, g/mL) NPs inhibit the rate of wound coverage. DNA damage assays confirmed TiO2 and ZnO NPs are genotoxic. In summary, hESC-Fib could be used as an alternative platform to understand toxicity profiles of metal oxide NPs.

Two-dimensional rheological laminar hemodynamics through a diseased tapered artery with a\ud mild stenosis present is simulated theoretically and computationally. The effect of different\ud metallic nanoparticles homogeneously suspended in the blood is considered, motivated by drug\ud delivery (pharmacology) applications. The Eringen micropolar model has been deployed for\ud hemorheological characteristics in the whole arterial region. The conservation equations for\ud mass, linear momentum, angular momentum (micro-rotation), and energy and nanoparticle\ud species are normalized by employing suitable non-dimensional variables. The transformed\ud equations are solved numerically subject to physically appropriate boundary conditions using\ud the finite element method with the variational formulation scheme available in the FreeFEM++\ud code. A good correlation is achieved between the FreeFEM++ computations and existing\ud results. The effect of selected parameters (taper angle, Prandtl number, Womersley parameter,\ud pulsatile constants, and volumetric concentration) on velocity, temperature, and microrotational (Eringen angular) velocity has been calculated for a stenosed arterial segment. Wall\ud shear stress, volumetric flow rate, and hemodynamic impedance of blood flow are also\ud computed. Colour contours and graphs are employed to visualize the simulated blood flow\ud characteristics. It is observed that by increasing Prandtl number (Pr), the micro-rotational\ud velocity decreases i.e., microelement (blood cell) spin is suppressed. Wall shear stress\ud decreases with the increment in pulsatile parameters (B and e), whereas linear velocity\ud increases with a decrement in these parameters. Furthermore, the velocity decreases in the\ud tapered region with elevation in the Womersley parameter (α). The simulations are relevant to\ud transport phenomena in pharmacology and nano-drug targeted delivery in hematology.

Nanoparticles with encapsulated small molecules have attained vital importance in anticancer research. Peptide-based nanoparticles show their versatility in drug delivery due to their excellent biocompatibility and nontoxic nature. We demonstrate here the design and fabrication of peptide-based nanoparticles as dual-therapeutic cargo for the controlled release of hydrophilic 5-Fluorouracil (5Fu) and hydrophobic camptothecin (CPT), simultaneously. The covalent conjugation of 5Fu with the peptide, through a stimuli-responsive linker, provided better control over the release of 5Fu and dramatically reduced the possibility of leaching of the small molecule. As anticipated, the peptide-5Fu nanoparticles were efficient to encapsulate a second chemotherapeutic molecule CPT in its hydrophobic region. The stimuli-responsive release of 5Fu was carefully monitored by HPLC, NMR, and UV-visible spectroscopy. On the other hand, the release of the hydrophobic drug CPT from the nanoparticles was determined to be in a diffusion-controlled fashion. Assessment of performance in human cervical HeLa cell lines demonstrated the peptide-drug nanoparticles to be highly nontoxic. Whereas, the simultaneous release of the two antitumor agents, in a controlled manner, resulting in rapid antiproliferation of the tumor cells.

Tellurite reducing bacterial strain was isolated from Zuari estuary, Goa India which could tolerate 5.5 mM potassium tellurite with a minimum inhibitory concentration of 6 mM. This strain was designated as GUSDZ9 and was identified as Shewanella baltica (accession number: MF350629 ) based on 16S rRNA gene sequencing and BLAST analysis. The Diethyl-dithiocarbamate based colorimetric analysis clearly demonstrated a complete reduction of 2 mM tellurite to elemental tellurium during the late stationary phase. Te Nanoparticles (TeNPs) biosynthesis which initiated at early log phase (i.e. 4 h) was evidently monitored through colour change and a peak due to surface plasmon resonance at 210 nm using UV–Vis spectroscopic analysis. X-ray crystallographic studies and transmission electron microscopy revealed unique nano-rods with a diameter ranging from 8 to 75 nm. Energy dispersive X-ray analysis further confirmed the presence of pure tellurium. The biogenic TeNPs at 10 and 5 µg/mL evidently demonstrated 90% degradation of methylene blue dye and anti-biofilm activity against potential Gram-positive and Gram-negative human pathogens respectively. The alkaline comet assay revealed time and dose-dependent genotoxicity at concentrations higher than 15 µg/mL of TeNPs. This study clearly demonstrated the potential of Shewanella baltica strain GUSDZ9 in bioremediation of toxic tellurite through bio-reduction into elemental tellurium and involvement of biogenic TeNPs in the photo-catalytic reduction of methylene blue and anti-biofilm activity. This is the first report of its kind on the synthesis of biogenic TeNPs from Shewanella baltica demonstrating photo-catalytic, anti-biofilm activity as well as genotoxicity.

The purpose of this study was to develop PEGylated nanoparticles of bendamustine (BM) to improve therapeutic efficiency of drug and reduce the side-effects. The nanoparticles were prepared by a modified diffusion-emulsification method. The particle size and zeta potential of optimized BM-loaded PEGylated NPs were found to be 256 nm and -29.1 mV. The in vitro release showed biphasic behavior, with initial burst release followed by slow sustained delivery. The anti-tumor activity was determined using the A- 549 cell line, by the MTT assay. The stability study revealed that the nanoparticles prepared were stable for 3 months at both 25°C and 4°C.

The unique physico-chemical properties of nano crystalline anatase titanium dioxide nanoparticles (TiO2 NPs) render them with different biological and chemical activities. Hence, it is widely used in industrial and consumer applications. Previous studies have shown the genotoxicity of TiO2 NPs. However, there is a paucity of data regarding mutagenicity of these NPs. In the present study, the cellular uptake, sub-cellular localization, cytotoxicity and short term DNA interaction of TiO2 NPs (1–100 μgmL−1) of diameter ranging from 12 to 25 nm on mammalian lung fibroblast cells (V-79) has been studied. The flow cytometric analysis and electron micrographs of V-79 monolayer showed the internalization of TiO2 NPs in the cytoplasm with the confirmation of elemental composition through SEM/EDX analysis. TEM analysis also showed TiO2 NPs induced ultra-structural changes such as swollen mitochondria and nuclear membrane disruption in V-79 cells. TiO2 NPs generated free radicals, which induced indirect mutagenic and genotoxic responses. Apart from measuring the genotoxicity by Comet assay, the mutagenic potential of TiO2 NPs in V-79 cells was evaluated by mammalian HGPRT gene forward mutation assay, showing a 2.98- fold increase in 6TGR HGPRT mutant frequency (*p

The current work focuses on the study of polymeric, biodegradable nanoparticles (NPs) for the encapsulation of doxorubicin and mitomycin C (anti-leishmanial drugs), and their efficient delivery to macrophages, the parasite's home. The biodegradable polymer methoxypoly-(ethylene glycol)-b-poly (lactic acid) (MPEG-PLA) was used to prepare polymeric NPs encapsulating doxorubicin and mitomycin C. The morphology, mean diameter, and surface area of spherical NPs were determined by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and BET surface area analysis. X-ray diffraction was performed to validate drug encapsulation. An in vitro release profile of the drugs suggested a fairly slow release. These polymeric NPs were efficiently capable of releasing drug inside macrophages at a slower pace than the free drug, which was monitored by epi-fluorescence microscopy. Encapsulation of doxorubicin and mitomycin C into NPs also decreases cellular toxicity in mouse macrophages (J774.1A).

Purpose: Systemic chemotherapy fails to access much of the tumor burden in patients with advanced cancer, significantly limiting its efficacy. In preclinical studies, brief high doses of tyrosine kinase inhibitors (TKI) targeting the human epidermal growth factor receptor (HER) family can prime tumor vasculature for optimal chemotherapeutic delivery and efficacy. This study investigates the clinical relevance of this approach. Experimental Design: A phase I clinical study of escalating doses of the HER TKI lapatinib given as a 2-day pulse before a weekly infusion of nab-paclitaxel (100 mg/m2) was conducted in patients with advanced solid tumors. Results: Twenty-five patients were treated. Treatment was associated with grade 1 to 2 toxicities including diarrhea, nausea, rash, neutropenia, neuropathy, fatigue, alopecia, and anemia. The two dose-limiting toxicities were grade 3 vomiting and grade 4 neutropenia, and the maximum tolerated dose of lapatinib was defined as 5250 mg/day in divided doses. Lapatinib concentrations increased with increasing dose. Dynamic Contrast Enhanced Magnetic Resonance Imaging studies in a subset of patients confirmed a decrease in tumor vascular permeability immediately following a lapatinib pulse. Sixty-five percent of evaluable patients experienced a partial or stable response on this therapy, 72% of whom were previously taxane-refractory. Conclusion: A 2-day pulse of high-dose lapatinib given before weekly nab-paclitaxel is a feasible and tolerable clinical regimen, suitable for testing this novel vascular-priming chemosensitization hypothesis developed in preclinical models. (Clin Cancer Res 2009;15(17):5569–75)

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.

We created and produced a novel self-assembling nanoparticle platform for delivery of peptide epitopes that induces CD8(+) and CD4(+)T cells that are protective against Toxoplasma gondii infection. These self-assembling polypeptide nanoparticles (SAPNs) are composed of linear peptide (LP) monomers which contain two coiled-coil oligomerization domains, the dense granule 7 (GRA720-28 LPQFATAAT) peptide and a universal CD4(+)T cell epitope (derived from PADRE). Purified LPs assemble into nanoparticles with icosahedral symmetry, similar to the capsids of small viruses. These particles were evaluated for their efficacy in eliciting IFN-γ by splenocytes of HLA-B*0702 transgenic mice and for their ability to protect against subsequent T. gondii challenge. This work demonstrates the feasibility of using this platform approach with a CD8(+) epitope that binds HLA-B7 and tests the biological activity of potentially protective peptides restricted by human major histocompatibility complex (HLA) class I molecules in HLA transgenic mice.

Neuroendocrine tumors often present a diagnostic and therapeutic challenge. We have aimed to synthesize and develop biodegradable nanoparticles of somatostatin analogue, octreotide for targeted therapy of human neuroendocrine pancreatic tumor.Direct solid phase peptide synthesis of octreotide was done. Octreotide loaded PCL/PEG nanoparticles were prepared by solvent evaporation method and characterized for transmission electron microscopy, differential scanning calorimetery (DSC), Zeta potential measurement studies. The nanoparticles were evaluated in vitro for release studies and peptide content. For biological evaluations, receptor bindingcytotoxicity studies were done on BON-1 neuroendocrine tumor cell line. Biodistribution of radiolabeled peptide and nanoparticles, tumor regression studies were performed on tumor-bearing mouse models.We have synthesized and purified octreotide with the purity of 99.96% in our laboratory. PEG/PCL nanoparticles with an average diameter of 130-195 nm having peptide loading efficiency of 66-84% with a negative surface charge were obtained with the formulation procedure. Octreotide nanoparticles have a negative action on the proliferation of BON-1 cells. In vivo biodistribution studies exhibited major accumulation of octreotide nanoparticles in tumor as compared to plain octreotide. Octreotide nanoparticles inhibited tumor growth more efficiently than free octreotide.Thus, it was concluded that the PCL/PEG nanoformulation of octreotide showed high tumor uptake due to the enhanced permeation and retention (EPR) effect and then peptide ligand imparts targetability to the sst2 receptor and there by showing increase tumor growth inhibition. Selective entry of nanoparticles to the tumor also give the reduce side effects both in vivo and in vitro.

Purpose: Solid lipid nanoparticles (SLN) have emerged as carriers for therapeutic peptides, proteins, antigens and bioactive molecules. We have explored the potential of SLN as carrier for Hepatitis B surface antigen (HBsAg) by surface modifications to enhance their loading efficiency and the cellular uptake, using subcutaneous route. Methods: Four different formulations of SLN were prepared by solvent injection method and characterized for various physical properties: particle size, surface morphology, shape, zeta potential, polydispersity, X-ray diffraction analysis, release profile and entrapment efficiency. HBsAg loaded SLN were studied for their functional characteristics, in vitro cellular uptake and internalization studies by human dendritic cells, macrophages and fibroblasts, T cell proliferation and TH1/TH2 response. Humoral immune response elicited by subcutaneously administered HBsAg containing SLN formulations were studied in vivo in mice. Results: Compared to soluble HBsAg; SLN, particularly the mannosylated formulation, showed better cellular uptake, lesser cytotoxicity and induction of greater TH1 type of immune response. They also showed better immunological potential by producing sustained antibody titer. Conclusion: Mannosylated SLN appears to be promising as carrier for vaccine delivery against hepatitis B as ascertained by in vitro and in vivo studies, however further investigations on humans are required to establish their potential as vaccines against hepatitis B infection.

Changes in mineral texture (e.g. hydroxyapatite (HAP) or aragonite) and polypeptide (e.g. tropocollagen (TC)) residue sequence are characteristic features of a disease known as osteogenesis imperfecta (OI). In OI, different possibilities of changes in polypeptide residue sequence as well as changes in polypeptide helix replacement (e.g. 3 alpha1 chains instead of 2 alpha1 and 1 alpha2 chain in OI murine) exist. The cross section of the HAP crystals could be needle like or plate like. Such texture and residue sequence related changes can significantly affect the material strength at the nanoscale. In this work, a mechanistic understanding of such factors in determining strength of nanoscale TC-HAP biomaterials is presented using three dimensional molecular dynamics (MD) simulations. Analyses point out that the peak interfacial strength for failure is the highest for supercells with plate shaped HAP crystals. TC molecules with higher number of side chain functional groups impart higher strength to the TC-HAP biomaterials at the nanoscale. Overall, HAP crystal shape variation, the direction of applied loading with respect to the relative TC-HAP orientation, and the number of side chain functional groups in TC molecules are the factor that affect TC-HAP biomaterial strength in a significant manner.