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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.

Pancreatic cancer is one of the harshest and most challenging cancers to treat, often labeled as incurable. Chemotherapy continues to be the most popular treatment yet yields a very poor prognosis. The main barriers such as inefficient drug penetration and drug resistance, have led to the development of drug carrier systems. The benefits, ease of fabrication and modification of liposomes render them as ideal future drug delivery systems. This review delves into the versatility of liposomes to achieve various mechanisms of treatment for pancreatic cancer. Not only are there benefits of loading chemotherapy drugs and targeting agents onto liposomes, as well as mRNA combined therapy, but liposomes have also been exploited for immunotherapy and can be programmed to respond to photothermal therapy. Multifunctional liposomal formulations have demonstrated significant pre-clinical success. Functionalising drug-encapsulated liposomes has resulted in triggered drug release, specific targeting, and remodeling of the tumor environment. Suppressing tumor progression has been achieved, due to their ability to more efficiently and precisely deliver chemotherapy. Currently, no multifunctional surface-modified liposomes are clinically approved for pancreatic cancer thus we aim to shed light on the trials and tribulations and progress so far, with the hope for liposomal therapy in the future and improved patient outcomes. Considering that conventional treatments for pancreatic cancer are highly associated with sub-optimal performance and systemic toxicity, the development of novel therapeutic strategies holds outmost relevance for pancreatic cancer management. Liposomes are being increasingly considered as promising nanocarriers for providing not only an early diagnosis but also effective, highly specific, and safer treatment, improving overall patient outcome. This manuscript is the first in the last 10 years that revises the advances in the application of liposome-based formulations in bioimaging, chemotherapy, phototherapy, immunotherapy, combination therapies, and emergent therapies for pancreatic cancer management. Prospective insights are provided regarding several advantages resulting from the use of liposome technology in precision strategies, fostering new ideas for next-generation diagnosis and targeted therapies of pancreatic cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

The utilization of alginate polymers for wound healing is well explored; however, little attention is paid toward the optimization of the manufacturing process, especially in regards to the final morphological and rheological properties that are imparted to the alginate matrix. This is important as it helps to establish a set of guidelines for the consistent fabrication of mechanically strong polymer wafers, which in the context of manufacturing and production contributes to the reduction in research and development time required. In this study, the order of application with respect to cross‐linking and freeze‐drying parameters has been investigated, which showed to result in distinct differences in terms of their overall morphology and mechanical strength. The application of freeze‐drying before cross‐linking results in the uniform distribution of cross‐links throughout the alginate wafer, thereby producing a mechanically strong polymer wafer that retains the dehydrated matrices original thickness and architecture. Based on the observed data, freeze‐drying prior to cross‐linking facilitates the increased permeation and distribution of the cross‐linker solution into the polymer matrix, thus resulting in the uniform distribution of ionic cross‐links, which is necessary to produce a more mechanically superior polymer matrix. [ABSTRACT FROM AUTHOR]

Introduction: Nano-scale formulations are being developed to improve the delivery of orally administered medicines, and the interactions between nanoformulations and the gastrointestinal luminal, mucosal and epithelial environment is currently being investigated. The mucosal surface of the gastrointestinal tract is capable of trapping and eliminating large particles and pathogens as part of the natural defences of the body, it is becoming clearer that nanoformulation properties such as particle size, charge, and shape, as well as mucous properties such as viscoelasticity, thickness, density, and turn-over time are all relevant to these interactions. However, progress has been slow to utilise this information to produce effective mucous-penetrating particles. Areas covered: This review focuses on delivery method of nanomedicines both into and across the gastrointestinal mucosal surface, and aims to summarise the biological barriers that exist to successful oral nanomedicine delivery and how these barriers may be investigated and overcome. Expert commentary: Despite successes in the laboratory, no nanotechnology-enabled products are currently in clinical use which either specifically target the intestinal mucous surface or cross the epithelial barrier intact. New nanomedicine-based treatments of local diseases (intestinal cancer, inflammation, infection) and systemic diseases are advancing towards clinical use, and offer genuine opportunities to improve therapy. [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 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]

Fluorescent amphiphilic polymers were produced by grafting different types and levels of hydrophobic pendant groups with intrinsic fluorescent properties (fluorenylmethoxy carbonyl (Fmoc), dimethylamino-1-naphthalenesulfonyl (Dansyl), and naphthalene (Naphth) to a water soluble homopolymer backbone, polyallylamine (PAA). Non-fluorescent hydrophobic pendant group (cholesteryl moieties) were also grafted onto PAA. The polymers were characterized with elemental analysis, NMR and FTIR spectroscopy. All polymers formed self-assemblies by probe sonication in water with sizes ranging from 120 to 199 nm and TEM images showed the presence of spherical particles. The critical aggregation concentration (CAC) varied from 0.093 to 1.5 mg ml−1 depending on the type of hydrophobic pendant groups. The Cholesteryl and Dansyl polymers showed the presence of one CAC while the Fmoc and Naphth grafted polymers revealed the presence of two CACs. The first CAC observed was possibly due to intermolecular aggregation while the second CAC at the higher polymer concentration was the result of excimer formation revealed by their fluorescent spectra. We reasoned that Naphth and Fmoc aromatic pendant groups possess a flat stereochemistry, thus allowing π- π stacking at higher concentrations. The presence of the N-dimethylamino group in the Dansyl moiety gives rise to a 3D structure, thus hindering any stacking. The understanding of the supramolecular assemblies formed by these fluorescent amphiphilic polymers will aid in the engineering of advanced materials with superior functionality for biomedical applications. Copyright © 2011 John Wiley & Sons, Ltd. [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]

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]

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]