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[Display omitted] By carefully controlling the dose administered and the drug release rate from drug-eluting implants, safety and efficacy of the therapeutic agent dispensed can be improved. The present work focuses on the promising advantages of 3D Bioprinting process in developing two layers' implantable scaffolds. The two layers have different functions, in order to ensure a more effective and synergistic breast cancer therapy. First layer involves use of polymers such as Poly- ε-Caprolactone (PCL) and Chitosan (CS), and incorporation of 5-Fluorouracil (5-FU). The aim of the first layer is releasing the drug within 4 weeks, obtaining a prolonged and modified release. According to in vitro drug release tests performed, ∼32 % of 5-FU was released after one month, after an initial burst effect of 17.22 %. The sudden release of the drug into the body would quickly reach an effective therapeutic concentration, while the drug sustained release maintains an effective therapeutic concentration range during the administration time. The second layer is made exclusively from PCL as polymeric matrix, into which Gold Nanoparticles (AuNPs) were subsequently loaded, and its main purpose is to be radiation enhancement. The long biodegradation time of PCL would make the non-soluble scaffold an alternative to conventional chemotherapy, optimizing drug release to the specific needs of the patients. [ABSTRACT FROM AUTHOR]

[Display omitted] By carefully controlling the dose administered and the drug release rate from drug-eluting implants, safety and efficacy of the therapeutic agent dispensed can be improved. The present work focuses on the promising advantages of 3D Bioprinting process in developing two layers' implantable scaffolds. The two layers have different functions, in order to ensure a more effective and synergistic breast cancer therapy. First layer involves use of polymers such as Poly- ε-Caprolactone (PCL) and Chitosan (CS), and incorporation of 5-Fluorouracil (5-FU). The aim of the first layer is releasing the drug within 4 weeks, obtaining a prolonged and modified release. According to in vitro drug release tests performed, ∼32 % of 5-FU was released after one month, after an initial burst effect of 17.22 %. The sudden release of the drug into the body would quickly reach an effective therapeutic concentration, while the drug sustained release maintains an effective therapeutic concentration range during the administration time. The second layer is made exclusively from PCL as polymeric matrix, into which Gold Nanoparticles (AuNPs) were subsequently loaded, and its main purpose is to be radiation enhancement. The long biodegradation time of PCL would make the non-soluble scaffold an alternative to conventional chemotherapy, optimizing drug release to the specific needs of the patients. [ABSTRACT FROM AUTHOR]

Natural products have been acknowledged for numerous years as a vital source of active ingredients in therapeutic agents. In particular, the use of active ingredients derived from plants for use in microbial natural products have long been used before the dawn of modern medicine. From ancient times, the efficacy of natural products has been associated with the chemistry, biochemistry and synthetic activities of natural products. Thus, with scientific advancement in modern molecular and cellular biology, analytical chemistry and pharmacology, the unique properties of these natural products are being harnessed in order to exploit the chemical and structural diversity and biodiversity of these types of products in relation to their therapeutic effect. Often, new molecules of interest in drug design units focus on the rearrangement of chemical entities or structural isomers of naturally occurring products in order to generate new molecules; these may be formulated into clinically useful therapies. [ABSTRACT FROM AUTHOR]

Background: Iron oxide nanoparticles (IONPs) have increasing applications in biomedicine, however fears over long term stability of polymer coated particles have arisen. Gold coating IONPs results in particles of increased stability and robustness. The unique properties of both the iron oxide (magnetic) and gold (surface plasmon resonance) result in a multimodal platform for use as MRI contrast agents and as a nano-heater. Results: Here we synthesize IONPs of core diameter 30 nm and gold coat using the seeding method with a poly (ethylenimine) intermediate layer. The final particles were coated in poly(ethylene glycol) to ensure biocompatibility and increase retention times in vivo. The particle coating was monitored using FTIR, PCS, UV-vis absorption, TEM, and EDX. The particles appeared to have little cytotoxic effect when incubated with A375M cells. The resultant hybrid nanoparticles (HNPs) possessed a maximal absorbance at 600 nm. After laser irradiation in agar phantom a ΔT of 32°C was achieved after only 90 s exposure (50 µgmL-1). The HNPs appeared to decrease T2 values in line with previously clinically used MRI contrast agent Feridex®. Conclusions: The data highlights the potential of these HNPs as dual function MRI contrast agents and nanoheaters for therapies such as cellular hyperthermia or thermo-responsive drug delivery. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the in vitro and in vivo pancreatic anticancer activity of a nano-sized formulation based on novel polyallylamine grafted with 5% mole cholesteryl pendant groups (CH-PAA). Methods: Insoluble novel anticancer drug, Bisnaphthalimidopropyldiaaminooctane (BNIPDaoct), was loaded into CH-PAA polymeric self-assemblies by probe sonication. Hydrodynamic diameters and polydispersity index measurements were determined by photon correlation spectroscopy. The in vitro cytotoxicity evaluation of the formulation was carried out by the sulforhodamine B dye assay with human pancreatic adenocarcinoma BxPC-3 cells, while for the in vivo study, Xenograff mice were used . In vitro apoptotic cell death from the drug formulation was confirmed by flow cytometric analysis. Results: The aqueous polymer-drug formulation had a mean hydrodynamic size of 183 nm. The drug aqueous solubility was increased from negligible concentration to 0.3 mg mL. CH-PAA polymer alone did not exhibit cytotoxicity, but the new polymer-drug formulation showed potent in vitro and in vivo anticancer activity. The mode of cell death in the in vitro study was confirmed to be apoptotic. The in vivo results revealed that the CH-PAA alone did not have any anti-proliferative effect, but the CH-PAA-drug formulation exhibited similar tumour reduction efficacy as the commercial drug, gemcitabine. Conclusions: The proposed formulation shows potential as pancreatic cancer therapeutics. [ABSTRACT FROM AUTHOR]

[Display omitted] The Diels-Alder reaction and its retro breakdown has garnered increasing research focus due to several of its advantageous properties including, atomic conservation, reversibility, and substituent retention. This is especially true in biomedical application and nanomedicine development which display a preference for rapid, efficient, and clean "click" chemistry reactions allowing for delivery of active ingredients and subsequent release upon temperature elevation. There are multiple variations on the Diels-Alder reaction based around substitution position and materials being coupled which can affect the temperature threshold for and rate of the retro reaction reversal. Hence, the Diels-Alder reaction offers a simple coupling reaction for active ingredients with tailorable release. In this review the incorporation of the Diels-Alder chemistries and linkers within the biomedical and nanomedicine field will be discussed, as well as its use in future potential technologies. [ABSTRACT FROM AUTHOR]

Cutaneous parasites are identified by their specific cutaneous symptoms which are elicited based on the parasite's interactions with the host. Standard anti-parasitic treatments primarily focus on the use of specific drugs to disrupt the regular function of the target parasite. In cases where secondary infections are induced by the parasite itself, antibiotics may also be used in tandem with the primary treatment to deal with the infection. Whilst drug-based treatments are highly effective, the development of resistance by bacteria and parasites, is increasingly prevalent in the modern day, thus requiring the development of non-drug based anti-parasitic strategies. Cutaneous parasites vary significantly in terms of the non-systemic methods that are required to deal with them. The main factors that need to be considered are the specifically elicited cutaneous symptoms and the relative cutaneous depth in which the parasites typically reside in. Due to the various differences in their migratory nature, certain cutaneous strategies are only viable for specific parasites, which then leads to the idea of developing an all-encompassing anti-parasitic strategy that works specifically against cutaneous parasites. The main benefit of this would be the overall time saved in regards to the period that is needed for accurate diagnosis of parasite, coupled with the prescription and application of the appropriate treatment based on the diagnosis. This review will assess the currently identified cutaneous parasites, detailing their life cycles which will allow for the identification of certain areas that could be exploited for the facilitation of cutaneous anti-parasitic treatment. [ABSTRACT FROM AUTHOR]

Wound management is a major contributor towards the economic burden placed upon the national health service (NHS), serving as an important target for the development of advanced therapeutic interventions. The economic expenditure of wound care for the NHS exceeds £5 billion per annum, thus presenting a significant opportunity for the introduction of alternative treatments in regards to their approach in tackling the ever increasing prevalence of wound management associated problems. As most wounds typically fall under the acute or chronic category, it is therefore necessary to design a therapeutic intervention capable of effectively resolving the pathologies associated with each problem. Such an intervention should be of increased economic viability and therapeutic effectiveness when compared to standardized treatments, thus helping to alleviate the financial burden imposed upon the NHS. The purpose of this review is to critically analyse the various aspects associated with wound management, detailing the fundamental concepts of dermal regeneration, whilst also providing an evaluation of the different materials and methods that can be utilised to achieve maximal wound regeneration. The primary aspects of this review revolve around the three concepts of antibacterial methodology, enhancement of dermal regeneration and the utilisation of a carrier medium to facilitate the regenerative process. Each aspect is explored, conveying its justifications as a target for dermal regeneration, whilst offering various solutions towards the fulfilment of a therapeutic design that is both effective and financially feasible. Image, graphical abstract [ABSTRACT FROM AUTHOR]

The control of the whitefly Bemisia tabaci relies heavily on the use of synthetic insecticides. There is a need to develop alternative control strategies due to concerns about impact of these insecticides on the environmental and human health, and the threat of insecticide resistance. Botanical oil extracts could potentially be used for the management of whiteflies and other pests. The study reported here therefore aimed to evaluate the efficacy of selected botanical oils against the cassava whitefly, B. tabaci and test their effect on its feeding behaviour. Patchouli oil treatment was the most effective at repelling whiteflies in no choice and choice experiments with up to 85% of whiteflies being repelled. Oviposition was also reduced 50–89% in patchouli. Neem was found to be effective at reducing oviposition, nymph and adult emergence by 50%, 70% and 80%, respectively, in a screenhouse no choice experiment. Patchouli significantly reduced the phloem ingestion phase (E2) by 40% and potential drops (pd) by 46% compared to control plants. Neem significantly increased the non‐probing duration by 48% and reduced pd by 50% compared to the control. Patchouli and neem were found to be the most effective among the selected botanical oils. These two oils should be further evaluated for efficacy under field conditions to determine suitability for recommendation as biopesticides against the cassava B. tabaci whitefly. [ABSTRACT FROM AUTHOR]

Anti-microbial resistance is a growing problem that has impacted the world and brought about the beginning of the end for the old generation of antibiotics. Increasingly, more antibiotics are being prescribed unnecessarily and this reckless practice has resulted in increased resistance towards these drugs, rendering them useless against infection. Nanotechnology presents a potential answer to anti-microbial resistance, which could stimulate innovation and create a new generation of antibiotic treatments for future medicines. Preserving existing antibiotic activity through novel formulation into or onto nanotechnologies can increase clinical longevity of action against infection. Additionally, the unique physiochemical properties of nanoparticles can provide new anti-bacterial modes of action which can also be explored. Simply concentrating on antibiotic prescribing habits will not resolve the issue but rather mitigate it. Thus, new scientific approaches through the development of novel antibiotics and formulations is required in order to employ a new generation of therapies to combat anti-microbial resistance. [ABSTRACT FROM AUTHOR]

Wound care is an integral part of effective recovery. However, its associated financial burden on national health services globally is significant enough to warrant further research and development in this field. In this study, multifunctional polymer wafers were prepared, which provide antibacterial activity, high cell viability, high swelling capacity and a thermally stable medium which can be used to facilitate the delivery of therapeutic agents. The purpose of this polymer wafer is to facilitate wound healing, by creating nanosilver particles within the polymer matrix itself via a one-pot synthesis method. This study compares the use of two synthetic agents in tandem, detailing the effects on the morphology and size of nanosilver particles. Two synthetic methods with varying parameters were tested, with one method using silver nitrate, calcium chloride and sodium alginate, whilst the other included aloe vera gel as an extra component, which serves as another reductant for nanosilver synthesis. Both methods generated thermally stable alginate matrices with high degrees of swelling capacities (400–900%) coupled with interstitially formed nanosilver of varying shapes and sizes. These matrices exhibited controlled nanosilver release rates which were able to elicit antibacterial activity against MRSA, whilst maintaining an average cell viability value of above 90%. Based on the results of this study, the multifunctional polymer wafers that were created set the standard for future polymeric devices for wound healing. These polymer wafers can then be further modified to suit specific types of wounds, thereby allowing this multifunctional polymer wafer to be applied to different wounding scenarios. [ABSTRACT FROM AUTHOR]

This study explored the synergistic effects of simultaneously using calcium and gallium cations in the cross-linking of alginate, detailing its effects on the characteristics of alginate compared to its single cation counterparts. The primary goal is to determine if there are any synergistic effects associated with the utilisation of multiple multivalent cations in polymer cross-linking and whether or not it could therefore be used in pharmaceutical applications such as wound healing. Given the fact divalent and trivalent cations have never been utilised together for cross-linking, an explanation for the mode of binding that occurs between the alginate and the cations during the cross-linking process and how it may affect the future applications of the polymer has been investigated. The calcium gallium alginate polymers were able to retain the antibacterial effects of gallium within the confines of the polymer matrix, possessing superior rheological properties, 6 times that of pure calcium and pure gallium, coupled with an improved swelling capacity that is 4 times higher than that of gallium alginate. [ABSTRACT FROM AUTHOR]

[Display omitted] • Enhancement of ECL signal for gemcitabine detection through gold nanoparticle addition is demonstrated. • Ability to now detect gemcitabine via the traditional [Ru(bpy) 3 ]2+ previously unattainable has been achieved. • Detection below therapeutically relevant ranges. With a rise in the development and subsequent employment of precision medicine, their lies an immediate necessity for the development of technology to enable the implementation of such treatment plans into the healthcare environment. Electrochemistry stands to offer one of the most viable techniques for such technologies given its success within current medical devices. One electrochemical technique, electrochemiluminescence (ECL), warrants investigation. Previously we have determined the inability to reliably detect cancer therapy gemcitabine via traditional ruthenium based ECL. Here we demonstrate how the addition of gold nanoparticles into the ECL film can promote GMB detection via enhanced electrocatalytic oxidation, generating the required ECL radicals. Via this approach we have been able to improve the ECL signal intensity 60-fold and achieve detection down to 6.25 µM across a linear range of 6.25–50 µM. Which lies within the therapeutically relevant range. This approach has successfully addressed the prior limitations encountered for the employment of traditional ruthenium based ECL for substance identification, where species exhibit limited electro-activity and suffer from electrochemically induced side reactions. [ABSTRACT FROM AUTHOR]

The physicochemical compatibility between amphiphilic polymers and hydrophobic drugs has been recognized as an important issue for improving the drug solubilisation in polymeric micelle formulations. In this work, poly-L-lysine (PLL) grafted by cholate pendants as the only hydrophobic moiety were synthesized in order to facilitate the solubilisation of sterol drugs. Results showed that micelles formed by cholate grafted PLL encapsulated significantly higher level of prednisolone and estradiol than palmitoylated PLL micelles, whereas the solubilisation capacity of non-sterol drug (griseofulvin) is inefficient for both polymers. This suggests that higher drug-polymer incorporation can be achieved by the inclusion of hydrophobic moieties with similar architecture as the drugs, i.e. 'drug-like' functional groups, which will be useful for the future design of colloidal systems for the encapsulation of specific drug. [ABSTRACT FROM AUTHOR]

Poly(allylamine) graft polymers have been shown to hold potential as drug delivery vehicles and complexation agents for biological molecules such as insulin. The nanoparticles formed upon aggregation or complexation allow for enhanced cellular trafficking resulting in enhanced efficacy. Multiple reports have shown the ease of synthesis and reliability of these graft polymers, however, little investigation into the effect of the molecular weight of the homopolymer poly(allylamine) has been carried out. In this work we synthesized a range of oxadiazole grafted poly(allylamine) derivatives of varied molecular weight (15, 17.5, 120 & 900 kDa) set at a 5% polymer:oxadiazole mole grafting. The effect of molecular weight on the size, critical aggregation concentration and drug loading/release was evaluated in model drugs before loading the optimal formulation with doxorubicin and carrying out a preliminary cytotoxicity study. In line with other cationic polymers, the larger poly(allylamine) amphiphilic derivatives resulted in greater drug loading, however, the particle size increased whilst drug loading dramatically decreased, which for cancer nanomedicine could be a barrier for pharmaceutical use. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles (NPs) were prepared using a polyol method from Fe(III) acetylacetonate in the presence of polyvinylpyrrolidone (PVP). These particles were subsequently calcined and annealed using a digitally controlled furnace from 200 to 1000 ̊C producing crystallization. The morphology of the untreated nanoclusters and each calcined NP sample were observed under a scanning electron microscope (SEM) coupled with energy-dispersive X-ray (EDX) and their correlation explored. The SEM confirmed that the spherical NPs produced by the polyol method maintained their morphology during calcination at different temperatures. The extent of agglomeration was analyzed using dynamic light spectroscopy (DLS), which were measured as 1.0 μm. The effect of calcination on structural changes was monitored by X-ray diffraction (XRD), this revealed the presence of both hematite (α-Fe 2 O 3) and maghemite (γ-Fe 2 O 3) phases at low temperatures and the complete transformation into hematite at higher temperature. UV–Visible and fluorescent spectroscopy were used to analyze the optical properties and vibratory sample magnetometer (VSM) confirmed its paramagnetic characters. • EG cum Calcination Method successively converted the iron organometallic into their complete hematite structures. • EG developed the definite morphology, which has not been affected during calcination and annealing. • FTIR exposed the gradual removal of organic part during calcination. • It explored the relation of optical absorbance and luminescence with structural change. • It has been characterized as paramagnetic material. [ABSTRACT FROM AUTHOR]

Poly[1,5-bis(N-pyrrolyl)pentane] (PBNPP) has been designed as a new addition to the modified polypyrrole family. This study entails the introduction of a pentane spacer between two pyrrole moieties and subsequently their oxidative polymerization under ambient conditions. The newly designed monomer and its polymer were fully characterized by FT-IR. The structural and optical behaviors were comparatively explored with reference to polypyrrole (Ppy), which was again prepared under same conditions. SEM was employed to visualize the morphology of PBNPP and Ppy comparatively. The data demonstrated the morphology of the PBNPP as spherical beads with a greater extent of surface porosity compared to Ppy, which possesses a compact granular form. The structural parameters were explored by XRD, where both possess crystallites of smaller size. Thermal behaviors were analyzed by TGA and DSC, where the newly designed polymer showed greater thermal stability and more plasticizing trend as compared to Ppy. Optical and HOMO-LUMO attributes have been characterized using UV-Vis spectrophotometer and diffused reflectance spectroscopy (DRS). The PBNPP demonstrated greater molar absorption and lesser HOMO-LUMO gap as compared to Ppy. The PBNPP was proposed as a suitable candidate for photoconductivity compared with the Ppy. Thus, the polymer produced from the modified pyrrole is thermally more stable, has high plasticizing character, reflects greater optically sensitivity, and possesses ease of electronic transition compared to its counterpart. [ABSTRACT FROM AUTHOR]

[Display omitted] Previously reported gold coated iron oxide nanoparticles (Au-IONP's) have demonstrated their effectiveness as drug delivery vehicles for gemcitabine conjugated to a thermally labile Diels-Alder linker containing a chain of 4 carbon atoms (TTLD4) for the treatment of pancreatic cancer. Heat generated via laser irradiation of Au-IONPs facilitated retro Diels-Alder mediated release in a burst release profile where approximately half of all total release over 180 min occurred within the first 5 min. Two analogues of TTLD4, which differ only in linker chain length (TTLD3 & TTLD6) were synthesised and conjugated to Au-IONP's. Heat-mediated release of gemcitabine at 45 °C over 180 min from these formulations was confirmed to be based on linker length, which was 94%, 76% and 45% for TTLD3, TTLD4 and TTLD6, respectively. Drug loading of the Diels-Alder linkers in a 5:1 Drug/Au-IONP w/w ratio appears to favour those containing an even number of carbons TTLD4 (76%) & TTLD6 (57%) over TTLD3 (25%), possibly due to the linker likely being positioned perpendicular to the Au-IONP surface because of the 120 °C–C bond. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis is a neglected tropical disease characterized by disfiguring skin lesions. Current chemotherapeutic options depend on toxic, expensive drugs that are both difficult to administer and becoming less effective due to increasing levels of resistance. In comparison, thermotherapy displays greater patient compliance and less adverse systemic effects, but there are still significant issues associated with this. The procedure is painful, requiring local anaesthetic, and is less effective against large lesions. Using nanoparticles to controllably generate heat in a localized manner may provide an alternative solution. Here we evaluate magnetic hyperthermia, using iron oxide magnetic nanoparticles, as a localized, heat-based method to kill the human-infective parasite in vitro. We assessed the effectiveness of this method against the differentiated, amastigote form of the parasite using three distinct viability assays: PrestoBlue, Live/Dead stain and a novel luciferase-based assay. Changes in amastigote morphology and ultrastructure were assessed by immunofluorescence, scanning and transmission electron microscopy. Our findings show that magnetic hyperthermia is an effective method to kill host-infective amastigotes, with morphological changes consistent with heat treatment. This method has the potential to be a step-change for research into new therapeutic options that moves away from the expensive chemotherapeutics currently dominating the research climate. [ABSTRACT FROM AUTHOR]

It is now established that the thieno[2,3-b]pyridines are a potent class of antiproliferatives. One of the main issues encountered for their clinical application is their low water solubility. In order to improve this, two strategieswere pursued. first, amorpholinemoietywas tethered to themolecular scaffold by substituting the sulphur atom with nitrogen, resulting in a 1H-pyrrolo[2,3-b]pyridine core structure. The water solubility was increased by three orders of magnitude, from 1.2 µg/mL (1-thieno[2,3-b]pyridine) to 1.3 mg/mL (3-pyrrolo[2,3-b]pyridine), however, it was only marginally active against cancer cells. The second strategy involved loading a very potent thieno[2,3-b]pyridine derivative (2) into a cholesteryl-poly(allylamine) polymermatrix for water solubilisation. Suppression of human pancreatic adenocarcinoma (BxPC-3) viability was observed to an IC50 value of 0.5 µg/mL (1.30 µM) in conjunction with the polymer, which is a five-fold (x5) increase in potency as compared to the free drug alone, demonstrating the utility of this formulation approach. [ABSTRACT FROM AUTHOR]

Pancreatic cancer has been classified as a cancer of unmet need. After diagnosis the patient prognosis is dismal with few surviving over 5 years. Treatment regimes are highly patient variable and often the patients are too sick to undergo surgical resection or chemotherapy. These chemotherapies are not effective often because patients are diagnosed at late stages and tumour metastasis has occurred. Nanotechnology can be used in order to formulate potent anticancer agents to improve their physicochemical properties such as poor aqueous solubility or prolong circulation times after administration resulting in improved efficacy. Studies have reported the use of nanotechnologies to improve the efficacy of gemcitabine (the current first line treatment) as well as investigating the potential of using other drug molecules which have previously shown promise but were unable to be utilised due to the inability to administer through appropriate routes--often related to solubility. Of the nanotechnologies reported, many can offer site specific targeting to the site of action as well as a plethora of other multifunctional properties such as image guidance and controlled release. This review focuses on the use of the major nanotechnologies both under pre-clinical development and those which have recently been approved for use in pancreatic cancer therapy. [ABSTRACT FROM AUTHOR]

Hybrid nanoparticles (HNPs) have shown huge potential as drug delivery vehicles for pancreatic cancer. Currently, the first line treatment, gemcitabine, is only effective in 23.8% of patients. To improve this, a thermally activated system was developed by introducing a linker between HNPs and gemcitabine. Whereby, heat generation resulting from laser irradiation of the HNPs promoted linker breakdown resulting in prodrug liberation. In vitro evaluation in pancreatic adenocarcinoma cells, showed the prodrug was 4.3 times less cytotoxic than gemcitabine, but exhibited 11-fold improvement in cellular uptake. Heat activation of the formulation led to a 56% rise in cytotoxicity causing it to outperform gemcitabine by 26%. In vivo the formulation outperformed free gemcitabine with a 62% reduction in tumor weight in pancreatic xenografts. This HNP formulation is the first of its kind and has displayed superior anti-cancer activity as compared to the current first line drug gemcitabine after heat mediated controlled release. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most prevalent causes of cancer mortality in women. In order to increase patient prognosis and survival rates, new technologies are urgently required to deliver therapeutics in a more effective and efficient manner. Niosome nanoparticles have been recently employed as therapeutic platforms capable of loading and carrying drugs within their core for both mono and combination therapy. Here, niosome-based nanoscale carriers were investigated as a targeted delivery system for breast cancer therapy. The platform developed consists of niosomes loaded with letrozole and cyclophosphamide (NLC) and surface-functionalized with a folic-acid-targeting moiety (NLCPFA). Drug release from the formulated particles exhibited pH-sensitive properties in which the niosome showed low and high release in physiological and cancerous conditions, respectively. The results revealed a synergic effect in cytotoxicity by co-loading letrozole and cyclophosphamide with an efficacy increment in NLCPFA use in comparison with NLC. The NLCPFA resulted in the greatest drug internalization compared to the non-targeted formulation and the free drug. Additionally, downregulation of cyclin-D, cyclin-E, MMP-2, and MMP-9 and upregulating the expression of caspase-3 and caspase-9 genes were observed more prominently in the nanoformulation (particularly for NLCPFA) compared to the free drug. This exciting data indicated that niosome-based nanocarriers containing letrozole and cyclophosphamide with controlled release could be a promising platform for drug delivery with potential in breast cancer therapy. [ABSTRACT FROM AUTHOR]

Hybrid iron oxide-gold nanoparticles are of increasing interest for applications in nanomedicine, photonics, energy storage, etc. However, they are often difficult to synthesise without experience or 'know-how'. Additionally, standard protocols do not allow for scale up, and this is significantly hindering their future potential. In this study, we seek to determine whether microfluidics could be used as a new manufacturing process to reliably produce hybrid nanoparticles with the line of sight to their continuous manufacture and scaleup. Using a Precision Nano NanoAssemblr Benchtop® system, we were able to perform the intermediate coating steps required in order to construct hybrid nanoparticles around 60 nm in size with similar chemical and physical properties to those synthesised in the laboratory using standard processes, with Fe/Au ratios of 1:0.6 (standard) and 1:0.7 (microfluidics), indicating that the process was suitable for their manufacture with optimisation required in order to configure a continuous manufacturing plant. [ABSTRACT FROM AUTHOR]

Hybrid nanoparticles (HNPs) such as iron oxide-gold nanoparticles are currently being exploited for their potential application in image-guided therapies. However, little investigation has been carried out into their physical or chemical stability and potential cytotoxicity in biological systems. Here, we determine the HNPs physical stability over 6 months and chemical stability in physiological conditions, and estimate the biological activity of uncoated and poly(ethylene glycol) coated nanoparticles on human pancreatic adenocarcinoma (BxPC-3) and differentiated human monocyte cells (U937). The potential of these HNPs to act as drug carrier vehicles was determined using the model drug 6-Thioguanine (6-TG). The data showed that the HNPs maintained their structural integrity both physically and chemically throughout the duration of the studies. In addition, negligible cytotoxicity or free radical production was observed in the cell lines tested. The 6-TG was successfully conjugated; with a ratio of 3:1:10 Fe:Au:6-TG (wt:wt:wt). After incubation with BxPC-3 cells, enhanced cellular uptake was reported with the 6-TG-conjugated HNPs compared with free drug along with a 10-fold decrease in IC. This exciting data highlights the potential of HNPs for use in image-guided drug delivery. [ABSTRACT FROM AUTHOR]

Fe3O4-Au hybrid nanoparticles (HNPs) have shown increasing potential for biomedical applications such as image guided stimuli responsive drug delivery. Incorporation of the unique properties of HNPs into thermally responsive scaffolds holds great potential for future biomedical applications. Here we successfully fabricated smart scaffolds based on thermo-responsive poly(N-isopropylacrylamide) (pNiPAM). Nanoparticles providing localized trigger of heating when irradiated with a short laser burst were found to give rise to remote control of bulk polymer shrinkage. Gold-coated iron oxide nanoparticles were synthesized using wet chemical precipitation methods followed by electrochemical coating. After subsequent functionalization of particles with allyl methyl sulfide, mercaptodecane, cysteamine and poly(ethylene glycol) thiol to enhance stability, detailed biological safety was determined using live/dead staining and cell membrane integrity studies through lactate dehydrogenase (LDH) quantification. The PEG coated HNPs did not show significant cytotoxic effect or adverse cellular response on exposure to 7F2 cells (p < 0.05) and were carried forward for scaffold incorporation. The pNiPAM-HNP composite scaffolds were investigated for their potential as thermally triggered systems using a Q-switched Nd:YAG laser. These studies show that incorporation of HNPs resulted in scaffold deformation after very short irradiation times (seconds) due to internal structural heating. Our data highlights the potential of these hybrid-scaffold constructs for exploitation in drug delivery, using methylene blue as a model drug being released during remote structural change of the scaffold. [ABSTRACT FROM AUTHOR]

[Display omitted] Thermally active polymers, can respond structurally to temperature changes, making them interesting as potential drug delivery vehicles. Polymers of N -(3-aminopropyl) methacrylamide hydrochloride (APMA) are cationic with primary amine groups in their structure, which have been explored in biomedical applications via post-polymerisation modifications. In this work, we synthesised amphiphilic APMA monomers using hydrophobic pendant groups via conjugation onto their primary amine group. The pendant groups chosen in this study were palmitoyl, dansyl and cholesteryl moieties. The amphiphilic monomers were subsequently copolymerized with N -(2-hydroxypropyl)methacrylamide (HPMA) using varied monomer feed ratios resulting in a thermo-responsive system. The ability of the resultant aggregates in aqueous solution to encapsulate and liberate model drugs (e.g., propofol, griseofulvin and prednisolone) was then determined. Our data showed that the HPMA based formulations were capable of loading the model drug molecules inside their lipophilic core; HPMA-co-(APMA-Dansyl 2%) exhibited the largest drug encapsulation ability. Subsequently, poly(ethylene glycol) (PEG) was incorporated into the intrinsic polymer structure. This resulted in a more rapid drug release profile, whereby 100% of griseofulvin and prednisolone were liberated after only 4 h, which was only 5% and 10% before the PEG inclusion, respectively. Similarly, propofol showed 70% liberation from the polymer aggregate after 24 h, compared with only 30% liberation pre-PEGylation. These studies give an insight into the potential of the HMPA based amphiphiles as thermally responsive cargo carrier/release systems which could be exploited in the delivery of poorly soluble drugs. [ABSTRACT FROM AUTHOR]

Simple Summary: The cellular mechanisms of drug resistance prevent the correct efficacy of the therapies used in various types of cancer and nanotechnology has been postulated as a possible alternative to avoid them. This review focuses on describing the different mechanisms of drug resistance and dis-covering which nanotechnology-based therapies have been used in recent years to evade them in colon (CRC) and pancreatic cancer (PAC). Here we summarize the use of different types of nanotechnology (mainly nanoparticles) that have shown efficacy in vitro and in vivo in preclinical phases, allowing future in-depth research in CRC and PAC and its translation to future clinical trials. The development of drug resistance is one of the main causes of cancer treatment failure. This phenomenon occurs very frequently in different types of cancer, including colon and pancreatic cancers. However, the underlying molecular mechanisms are not fully understood. In recent years, nanomedicine has improved the delivery and efficacy of drugs, and has decreased their side effects. In addition, it has allowed to design drugs capable of avoiding certain resistance mechanisms of tumors. In this article, we review the main resistance mechanisms in colon and pancreatic cancers, along with the most relevant strategies offered by nanodrugs to overcome this obstacle. These strategies include the inhibition of efflux pumps, the use of specific targets, the development of nanomedicines affecting the environment of cancer-specific tissues, the modulation of DNA repair mechanisms or RNA (miRNA), and specific approaches to damage cancer stem cells, among others. This review aims to illustrate how advanced nanoformulations, including polymeric conjugates, micelles, dendrimers, liposomes, metallic and carbon-based nanoparticles, are allowing to overcome one of the main limitations in the treatment of colon and pancreatic cancers. The future development of nanomedicine opens new horizons for cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Diagnostic approaches and chemotherapeutic delivery based on nanotechnologies, such as nanoparticles (NPs), could be promising candidates for the new era of cancer research. Recently great attention has been received by carbon-based nanomaterials such as Carbon Dots (CDs), due their variegated physical-chemical properties that makes these systems appealing for multiple use from bioimaging, biosensing, nano-carriers for drug delivery systems to innovative therapeutic agents in photodynamic (PDT) and photothermal therapy (PTT). In this review, we report the last evidence on the application and prospects of CDs as useful nano theranostics tools for cancer diagnosis and therapy. Carbon Dots (CDs) are the latest members of carbon-based nanomaterials, which since their discovery have attracted notable attention due to their chemical and mechanical properties, brilliant fluorescence, high photostability, and good biocompatibility. Together with the ease and affordable preparation costs, these intrinsic features make CDs the most promising nanomaterials for multiple applications in the biological field, such as bioimaging, biotherapy, and gene/drug delivery. This review will illustrate the most recent applications of CDs in the biomedical field, focusing on their biocompatibility, fluorescence, low cytotoxicity, cellular uptake, and theranostic properties to highlight above all their usefulness as a promising tool for cancer diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Diffuse intrinsic pontine gliomas (DIPGs) are the most aggressive high-grade gliomas known to affect children. Due to the infiltrative nature of the DIPG tumours in the brainstem, they are very difficult to treat. Unfortunately, children succumb to their disease within 1–2 years from their diagnosis. Novel therapeutic treatments are, thus, urgently needed. Using primary cultures and orthotopic models of DIPG, we evaluated the therapeutic efficacy of passionfruit like nanoarchitectures functionalized with human serum albumin and loaded with doxorubicin (NA-HSA-Dox). We found that NA-HSA-Dox were significantly effective at penetrating DIPG spheroids and subsequently at reducing the proliferation and colony formation in DIPG cells. Although an antitumour effect was not observed in orthotopic models of DIPG, NA-HSA-Dox was well tolerated. These study demonstrates the importance of employing brain tumour orthotopic models for the identification of novel therapies and the need to develop treatments that effectively cross the blood brain barrier. Diffuse Intrinsic Pontine Gliomas (DIPGs) are highly aggressive paediatric brain tumours. Currently, irradiation is the only standard treatment, but is palliative in nature and most patients die within 12 months of diagnosis. Novel therapeutic approaches are urgently needed for the treatment of this devastating disease. We have developed non-persistent gold nano-architectures (NAs) functionalised with human serum albumin (HSA) for the delivery of doxorubicin. Doxorubicin has been previously reported to be cytotoxic in DIPG cells. In this study, we have preclinically evaluated the cytotoxic efficacy of doxorubicin delivered through gold nanoarchitectures (NAs-HSA-Dox). We found that DIPG neurospheres were equally sensitive to doxorubicin and doxorubicin-loaded NAs. Colony formation assays demonstrated greater potency of NAs-HSA-Dox on colony formation compared to doxorubicin. Western blot analysis indicated increased apoptotic markers cleaved Parp, cleaved caspase 3 and phosphorylated H2AX in NAs-HSA-Dox treated DIPG neurospheres. Live cell content and confocal imaging demonstrated significantly higher uptake of NAs-HSA-Dox into DIPG neurospheres compared to doxorubicin alone. Despite the potency of the NAs in vitro, treatment of an orthotopic model of DIPG showed no antitumour effect. This disparate outcome may be due to the integrity of the blood-brain barrier and highlights the need to develop therapies to enhance penetration of drugs into DIPG. [ABSTRACT FROM AUTHOR]

Simple Summary: Transferrin receptor one (TFR-1), recognized by ferritin, is overexpressed in many tumor cells. This feature has been exploited to produce a selective overload of drugs within tumor cells by creating an engineered ferritin nanocage loaded with doxorubicin (HFn(DOX)). This bionanotechnology has been tested in human cancer, but there are no studies in veterinary oncology. This work, after evaluating the expression of TFR-1 in feline tumors, demonstrated for the first time the effectiveness in vitro of this nanocage in animals. These results confirm that engineered bionanocages also offer unprecedented opportunities for animal cancer to be applied in veterinary medicine and in comparative studies including spontaneous animal models of cancer. The transferrin receptor 1 (TFR-1) has been found overexpressed in a broad range of solid tumors in humans and is, therefore, attracting great interest in clinical oncology for innovative targeted therapies, including nanomedicine. TFR-1 is recognized by H-Ferritin (HFn) and has been exploited to allow selective binding and drug internalization, applying an HFn nanocage loaded with doxorubicin (HFn(DOX)). In veterinary medicine, the role of TFR-1 in animal cancers remains poorly explored, and no attempts to use TFR-1 as a target for drug delivery have been conducted so far. In this study, we determined the TFR-1 expression both in feline mammary carcinomas during tumor progression, as compared to healthy tissue, and, in vitro, in a feline metastatic mammary cancer cell line. The efficacy of HFn(DOX) was compared to treatment with conventional doxorubicin in feline mammary cancer cells. Our results highlighted an increased TFR-1 expression associated with tumor metastatic progression, indicating a more aggressive behavior. Furthermore, it was demonstrated that the use of HFn(DOX) resulted in less proliferation of cells and increased apoptosis when compared to the drug alone. The results of this preliminary study suggest that the use of engineered bionanocages also offers unprecedented opportunities for selective targeted chemotherapy of solid tumors in veterinary medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent decades, a molecular complex referred to as vault nanoparticle has attracted much attention by the scientific community, due to its unique properties. At the molecular scale, it is a huge assembly consisting of 78 97-kDa polypeptide chains enclosing an internal cavity, wherein enzymes involved in DNA integrity maintenance and some small noncoding RNAs are accommodated. Basically, two reasons justify this interest. On the one hand, this complex represents an ideal tool for the targeted delivery of drugs, provided it is suitably engineered, either chemically or genetically; on the other hand, it has been shown to be involved in several cellular pathways and mechanisms that most often result in multidrug resistance. It is therefore expected that a better understanding of the physiological roles of this ribonucleoproteic complex may help develop new therapeutic strategies capable of coping with cancer progression. Here, we provide a comprehensive review of the current knowledge. The vault nanoparticle is a eukaryotic ribonucleoprotein complex consisting of 78 individual 97 kDa-"major vault protein" (MVP) molecules that form two symmetrical, cup-shaped, hollow halves. It has a huge size (72.5 × 41 × 41 nm) and an internal cavity, wherein the vault poly(ADP-ribose) polymerase (vPARP), telomerase-associated protein-1 (TEP1), and some small untranslated RNAs are accommodated. Plenty of literature reports on the biological role(s) of this nanocomplex, as well as its involvement in diseases, mostly oncological ones. Nevertheless, much has still to be understood as to how vault participates in normal and pathological mechanisms. In this comprehensive review, current understanding of its biological roles is discussed. By different mechanisms, vault's individual components are involved in major cellular phenomena, which result in protection against cellular stresses, such as DNA-damaging agents, irradiation, hypoxia, hyperosmotic, and oxidative conditions. These diverse cellular functions are accomplished by different mechanisms, mainly gene expression reprogramming, activation of proliferative/prosurvival signaling pathways, export from the nucleus of DNA-damaging drugs, and import of specific proteins. The cellular functions of this nanocomplex may also result in the onset of pathological conditions, mainly (but not exclusively) tumor proliferation and multidrug resistance. The current understanding of its biological roles in physiological and pathological processes should also provide new hints to extend the scope of its exploitation as a nanocarrier for drug delivery. [ABSTRACT FROM AUTHOR]

Nanoparticles have been shown to be effective drug carriers in cancer therapy. Pancreatic cancer forms dense tumours which are often resistant to drug molecules. In order to overcome such multidrug resistance, new drug entities, novel delivery systems and combination therapy strategies are being explored. In this paper, we report the design and synthesis of a poly(allylamine)-based amphiphile modified with hydrophobic naphthalimido pendant groups. Bisnaphthalimide compounds have been shown to possess anticancer activity. The potential of this polymer to encapsulate, solubilize and enhance drug (5-fluorouricil and bis-(naphthalimidopropyl)-diaminooctane) cytotoxicity in BxPC-3 cells was evaluated. Our studies showed that the insoluble drugs could be formulated up to 4.3 mg mL−1 and 2.4 mg mL−1 inside the amphiphiles, respectively. Additionally, the novel poly(allylamine)-naphthalimide carrier resulted in an amplification of cytotoxic effect with drug treatment after 24 h, and was capable of reduction of 50% cell population at concentrations as low as 3 μg mL−1. [ABSTRACT FROM AUTHOR]

Nanoscale polymers systems have dominated the revolution of drug delivery advancement. Their potential in the fight against cancer is unrivalled with other technologies. Their functionality increase, targeting ability and stimuli responsive nature have led to a major boom in research focus. This review article concentrates on the use of these smart polymers in cancer therapy. Nanotechnologies have shown potential as drug carriers leading to increased drug efficacy and penetration. Multifunctional smart carriers which can release their payload upon an external or internal trigger such as pH or temperature are proving to be major frontrunners in the development of effective strategies to overcome this disease with minimal patient side effects. [ABSTRACT FROM AUTHOR]

Liver cancer treatments are often hindered by poor drug physicochemical properties, hence there is a need for improvement in order to increase patient survival and outlook. Combination therapies have been studied in order to evaluate whether increased overall efficacy can be achieved. This study reports the combined treatment of liver cancer cells with a combination treatment of chemotherapeutic agent paclitaxel and pro-apoptotic protein cytochrome C. In order to administer both agents in a single formulation, a poly(allylamine)-based amphiphile has been fabricated with the incorporation of a hybrid iron oxide-gold nanoparticle into its structure. Here, the insoluble paclitaxel becomes incorporated into the hydrophobic core of the self-assemblies formed in an aqueous environment (256 nm), while the cytochrome C attaches irreversibly onto the hybrid nanoparticle surface via gold-thiol dative covalent binding. The self-assemblies were capable of solubilising up to 0.698 mg/mL of paclitaxel (700-fold improvement) with 0.012 mg/mL of cytochrome C also attached onto the hybrid iron oxide-gold nanoparticles (HNPs) within the hydrophobic core. The formulation was tested on a panel of liver cancer cells and cytotoxicity was measured. The findings suggested that indeed a significant improvement in combined therapy (33-fold) was observed when compared with free drug, which was double the enhancement observed after polymer encapsulation without the cytochrome C in hepatocellular carcinoma (Huh-7D12) cells. Most excitingly, the polymeric nanoparticles did result in improved cellular toxicity in human endothelian liver cancer (SK-hep1) cells, which proved completely resistant to the free drug. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is an aggressive form of liver cancer that displays minimal symptoms until its late stages. Unfortunately, patient prognosis still remains poor with only 10% of patients surviving more than five years after diagnosis. Current chemotherapies alone are not offering efficient treatment, hence alternative therapeutic approaches are urgently required. In this work, we highlight the potential of combination of treatment of hepatocellular carcinoma with existing chemotherapies in combination with pro-apoptotic factor cytochrome C. In order to allow cytochrome C to cross the cellular membrane and become internalized, it has been immobilised onto the surface of hybrid iron oxide-gold nanoparticles. This novel approach has been tested in vitro on HepG2, Huh-7D and SK-hep-1 cell lines in order to elucidate potential as a possible alternative therapy with greater efficacy. The data from our studies show consistently that combining treatment of clinically used anticancer agents (doxorubicin, paclitaxel, oxaliplatin, vinblastine and vincristine) significantly increases the levels of apoptosis within the cell lines, which leads to cellular death. Hence, this combined approach may hold promise for future treatment regimes. [ABSTRACT FROM AUTHOR]