Search

Bladder cancer (BCa) is one of the most prevalent cancers worldwide. The effectiveness of intravesical therapy for bladder cancer, however, is limited due to the short dwell time and the presence of permeation barriers. Considering the histopathological features of BCa, the permeation barriers for drugs to transport across consist of a mucus layer and a nether tumor physiological barrier. Mucoadhesive delivery systems or mucus-penetrating delivery systems are developed to enhance their retention in or penetration across the mucus layer, but delivery systems that are capable of mucoadhesion-to-mucopenetration transition are more efficient to deliver drugs across the mucus layer. For the tumor physiological barrier, delivery systems mainly rely on four types of penetration mechanisms to cross it. This review summarizes the classical and latest approaches to intravesical drug delivery systems to penetrate BCa.

Hydrogels are soft materials consisting of a three-dimensional network of polymer chains. Over the years, hydrogels with different compositions have been developed as drug carriers for diverse biomedical applications, ranging from cancer therapy and wound care to the treatment of neurodegenerative and inflammatory diseases. Most of these carriers, however, are designed only to deliver single agents. Carriers based on hydrogels for co-delivery of multiple agents, with the release rate of each of the co-delivered agents tunable, are lacking. This study reports a one-pot method of fabricating alginate-based complex fibers with the Janus morphology, with carboxymethyl cellulose sodium functioning as a polymeric modifier of the properties of each of the fiber compartments. By using malachite green and minocycline hydrochloride as model drugs, the generated fibers demonstrate the capacity of enabling the release profile of each of the co-delivered drugs to be precisely controlled. Along with their negligible toxicity and the retention of the activity of the loaded drugs, the complex fibers reported in this study warrant further development and optimization for applications that involve co-delivery of multiple agents., Graphical abstract Alginate-based complex fibers with the Janus morphology were generated using a one-pot method and were shown to demonstrate the capacity of enabling the release profile of each of the co-delivered drugs to be precisely manipulated.Image, graphical abstract

Background Epigallocatechin-3-gallate (EGCG) is the most abundant and pharmaceutically active polyphenol in green tea. It shows diverse health-promoting effects, but due to its low oral bioavailability, its use in functional food development has been impeded. Over the years, the health-promoting effects of EGCG have been extensively reviewed; however, discussions of the possible use of EGCG in food development have been scant, even though copious ready-to-drink green tea beverages and nutritional supplements are available in the market. Scope and approach The hopes and hypes involved in the use of EGCG in functional food development will be explored based on recent studies. Implications for future efforts to manipulate the properties of EGCG for food applications will be presented. Key findings and conclusions Recent advances in technologies for structural modification and therapeutics delivery may enhance the food applications of EGCG. Despite this, justifications on the use of EGCG in functional food development should be seriously evaluated until a consensus is reached in terms of the safety and efficiency.

miRNA is a class of short noncoding RNA that regulates gene expression at the post-transcriptional level. Evidence of age-associated changes in miRNA expression has been collected in models ranging from nematodes to humans; however, there has been little discussion of how to turn our knowledge of miRNA biology into antiaging therapy. This opinion article provides a snapshot of our current understanding of the roles of miRNA in modulating the aging process. We discuss major chemical techniques for modifying the miRNA structure as well as developing delivery systems for intervention. Finally, technical needs to be met for bench-to-clinic translation of miRNA-based interventions are highlighted for future research.

Chitosan (CS) is a biodegradable and biocompatible polysaccharide which displays immune-stimulatory effects and anti-bacterial properties to facilitate wound closure. Over the years, different CS-based dressings have been developed; however, most of them are not fully biodegradable due to the involvement of synthetic polymers during dressing fabrication. In addition, preparation of many of these dressings is laborious, and may impose damaging effects on fragile therapeutic molecules. The objective of this study is to address these problems by developing a tunable, biocompatible, and biodegradable CS-based dressing for wound treatment. The dressing is fabricated via electrostatic interactions between CS and carmellose (CM). Its swelling properties, erosion behavior, loading efficiency and drug release sustainability can be tuned by simply changing the CS/CM mass-to-mass ratio. Upon loaded with minocycline hydrochloride, the dressing effectively protects the wound in mice from infection and enhances wound closure. Regarding its high tunability and promising in vivo performance, our dressing warrants further development as a user-friendly dressing for use in wound care.

A Forster resonance energy transfer (FRET)-based biosensor using Cu nanoclusters (NCs) as energy donors and signal magnifiers and MnO2 nanospheres as both energy acceptors and target recognizers for selective detection of glutathione (GSH) was developed. MnO2 nanospheres, synthesized through an ultrasonication assisted top down method, can quench the photoluminescence (PL) of Cu NCs through FRET, after forming complex through electrostatic interactions. GSH can recover PL of Cu NCs by triggering the decomposition of complex through digesting MnO2 nanospheres into Mn2+. Additionally, the PL can be further magnified through the host-guest interactions between GSH and Cu NCs, with around 25 times higher than the original intensity and 3 times higher than the initial PL intensity of Cu NCs. Under the optimum conditions, the FRET based sensor can detect GSH in the concentration range from 0 to 140 μM, with a detection limit of 17 μM. Moreover, the proposed method shows a strong anti-interference ability, achieving the sensitive directly detection of GSH in human whole blood samples. Our results provide insights in designing FRET based sensors. Moreover, all the components are nontoxic and biodegradable, demonstrating their potential applications in other fields such as nanomedicine and environmental science.

The development of composite hydrogels is enjoying ever-increasing research interests and applications due to the high flexibility of these materials in composition and properties. This study develops an emulsion-templated hydrogel-microsphere composite with tunable properties using a one-pot synthetic approach. The composite consists of poly(trimethylolpropane ethoxylate triacrylate) microspheres crosslinked by a hydrogel, which is formed by a starch-based bifunctional emulsion stabilizer. Composites with a higher compositional ratio of the hydrogel have been found to have lower erosion susceptibility and swelling capacity. As an illustration of the unique practical potential of its amphiphilic character and tunable swelling properties, as well as its large surface area for adsorption, the composite has been loaded with model compounds with various degrees of hydrophilicity, and has been shown to be useful for applications such as drug loading and pollutant removal. The composite is a novel material displaying application potential that warrants further development.

Development of carriers with tunable properties can enhance the controllability of the process of bioactive agent delivery. This study reports a self-indicating gel fabricated from a cellulose-based derivative, designated as CT, for controlled release of the loaded bioactive agent. By increasing the concentration of CT, the swelling and erosion rates of the gel are significantly reduced, with the encapsulation efficiency and release sustainability of the gel being substantially enhanced. Such changes in delivery performance can be manifested as changes in the intensity of intrinsic luminescence of the gel, enabling the gel to display self-indicating capacity. By using paclitaxel as a model agent, the gel is demonstrated in vivo to effectively reduce the systemic toxicity of the administered agent. Along with its excitation wavelength-dependent emission tunability which allows the wavelength of the excitation source to be changed for convenience and need, our gel shows high potential to be exploited as a self-indicating carrier for delivery of bioactive agents.

Hydrogels are swellable polymer networks which can imbibe a substantial amount of fluids. Compared to bulk hydrogels, hydrogel nanoparticles exhibit added values in drug delivery because they can be internalized into cells to deliver pharmaceutical agents into the cytosol. Their large surface area also allows for multivalent conjugations, making optimization of the nanoparticles towards in vivo and clinical applications possible. These features, together with the tunable properties and biocompatibility of hydrogels, account for the widespread use of hydrogel-based nanoparticulate systems in drug formulation. From an in vivo perspective, this article presents the latest advances in fabrication and engineering of hydrogel nanoparticles, and illuminates future avenues to enhance the potential of hydrogel-based nanoparticulate systems in treatment development and drug administration.

Sustained-release carriers with intrinsic luminescence exhibit the potential to combine imaging with bioactive agent delivery in practice. This study reports the synthesis and properties of CT, which is a gel-forming and highly tunable non-conjugated polymer with intrinsic luminescence. Owing to the excitation wavelength-dependent emission tunability of CT, optical imaging can be performed in a wide range of excitation wavelengths. This study is the first proof-of-concept study successfully integrating the property of clusterization-triggered emission into carrier design for combining imaging with bioactive agent delivery. By using cancer therapy as a practical example, our results demonstrate that CT is a depot system that cannot only enhance in vivo antitumor efficacy but can also allow its location and gelation process to be tracked in real time by giving an intrinsic blue-colored fluorescence signal. Together with its high biocompatibility, CT shows high practical potential for executing self-illuminating therapy to tackle cancer.

Luminescence plays an important role in advancing various research fronts. Traditionally, luminescence from polymeric luminogens is attributed to the presence of conjugated structures. In recent years, efforts have, however, been directed to deciphering the photophysics of polymeric luminogens in which conjugated structures are absent. These non-conjugated polymers do not experience aggregation-caused quenching as the conventional ones do. Instead, they display aggregation induced emission (AIE)-like properties. Because many dosage forms and carrier types (including tablets, microgels, nanoparticles, and films) exist in a highly aggregated state or solid state, non-conjugated polymeric luminogens exhibit potential for use in drug delivery. The objectives of this article are to highlight the practical potential of these luminogens as intrinsically luminescent carriers for drug delivery, and to revisit the opportunities and challenges of using them in theranostics.

DNA-nanotechnology based on DNA scaffolding technique is an established approach to formulate water-miscible nano-structural frameworks. We have designed the hydrophilic DNA-nanotubes (D-NTs) as a (water-soluble) vehicle to encapsulate a water-insoluble DNA-intercalating anticancer drug. Bleomycin (BM) is a model hydrophobic anticancer drug used in this study capable to bind with the D-NTs to formulate BM loaded D-NTs. This BM@D-NTs system was evaluated for the improvement of the in vitro anti-cancer effects on the resistant prostate cancer xenograft CWR22R cells, over-expressed with the folate receptors/alpha (FRα). D-NTs were functionalized with the FRα-targeting antibodies to interact with the FRα (receptors) highly expressed on the resistant prostate cancer xenograft CWR22R cells. D-NTs not only increased the aqueous miscibility/dispersibility of BM but also enhanced the therapeutic efficiency as a targeted (site-specific) drug delivery system. D-NTs synthesis was achieved by sticky ends cohesions of DNA triangular tiles. DNA triangles were self-assembled from a freshly circularized short scaffold chain (84-NT) by annealing with the various staple strands. The polymerization of the triangular tiles gave rise to DNA-nanosheet lattices which underwent morphological transition guided by the twists in the DNA duplexes. This DNA double helix curvature caused self-coiling of the DNA 2D nano-sheets to condense into D-NTs morphology. Native-Page gel experiment showed decreased electrophoretic mobility down the gel confirming the successful execution of the polymerized lattices via sticky ends cohesion of the DNA-triangles. The final morphology and self-coiling of 2D DNA nano-sheets were confirmed through atomic force microscopy (AFM) showed the successful synthesis of D-NTs having diameter 3 to 5 μm and length 200 to 600 nm. BM was loaded onto D-NTs via incubation of hydro-alcoholic solution of the BM with the aqueous solution of D-NTs followed by the evaporation of alcohol and intercalation of the BM onto D-NTs. The intercalation of BM onto D-NTs was confirmed by UV-shift analysis. The targeted cytotoxicity of the BM@D-NTs for the CWR22R (resistant prostate cancer xenograft) cells was confirmed through MTT assay and the flow cytometry compared to the highly compatible empty D-NTs. Confocal microscopy revealed the time-dependent transfection of BM@D-NTs into CWR22R cells compared to the control cell line.

DNA is known to be a life material that has been explored as an exciting biomaterial for bio-sensing, bio-imaging, and analytical applications. The current review focuses on describing the general concept of DNA nanotechnology including linear DNA nanotechnology, short circular DNA nanotechnology, DNA origami, and the hybrid protein–DNA nanotechnology/supramolecular approaches. We will further describe the existing strategies for the development of DNA molecular tension probes to target the cell surface receptors (mainly integrin) for bio-imaging and bio-sensing applications. The surface activation of the cellular receptors by the DNA probes will elicit the mechanical responses to the cells for the analysis and bio-imaging of mechano-biological processes. The literature overview is obvious about the role of cell surface receptors in generating piconewton (pN) forces and carrying out mechano-transduction events necessary for the growth, development, and proper functioning of the cells. The last part of the review will briefly summarize our contribution as a latest advancement in this field, and to establish a further need for research.

DNA based nano-carriers synthesized from short circular scaffolds (circular DNA nanotechnology) attains stiffer topology for ligand functionalization (neuregulin-1/NRG-1 ligand) and biological applications (targeted drug delivery). Daunorubicin (DR) is a hydrophobic chemical that requires robust vectors to efficiently encapsulate and avoid its free dispersion in water, biological media and cell culture. Here we design DNA nanospindels (DNA-NS) to efficiently load DR and target the (highly expressed) HER2/neu receptors on the plasma membrane of drug-resistant MCF-7 (breast cancer) cells. DNA-NS were synthesized by polymerizing the DNA-triangles (utilizing 84-nt short circular scaffold strand) into larger DNA nano-ribbons characterized by the native-PAGE testing. AFM results revealed the spinning of DNA nanoribbons on its (own) axis because of the intrinsic curvature of the DNA double helix resulting in the formation of the firm and twisted DNA-NS with the diameter (50–70 nm) and length (0.5–4 μm). DA loading onto DNA-NS was confirmed by the UV shift analysis. The MTT results with the blank DNA-NS evidenced its biocompatibility (remained value of 93%) compared to the decreased viability of the MCF-7 cells after treatment with DNA-NS (DR loaded). These findings were further supported by the analysis of cell proliferation/apoptosis through flow cytometry showing 64% apoptosis after treating with the DR loaded DNA-NS. Hence, through the short circular DNA nanotechnology, we have achieved a stiffer, uniform, and biocompatible DNA-NS for applications in the targeted therapy.

In this work, copper nanoclusters (CuNCs), in which cysteine served as both a reducing agent and a protection ligand, were synthesized, and impregnated into a nanogel of glycol chitosan (GC), forming a CuNCs@GC nanocomposite. The stability of CuNCs incorporated into a nanogel was significantly improved, while their photoluminescence (PL) intensity of CuNCs@GC could be tuned by controlling the pH of the system. The nanocomposite was used as a platform for the “turn on” detection of Zn2+, making use of the effect of aggregation induced emission (AIE) enhancement. By adjusting the pH of the system to 7.4, the PL of CuNCs@GC was turned down so as to minimize the background signal. In the presence of Zn2+, the nanoclusters in CuNCs@GC changed from the dispersed state to the aggregated state, which resulted in an increase of the PL intensity. A linear response between the PL intensity and the concentration of Zn2+, in the range from 1.5 μM to 750 μM, was obtained, achieving a detection limit of 1.0 μM. Furthermore, the CuNCs@GC nanocomposite was found to be applicable to live cell imaging, owing to the high biocompatibility and protective effects of GC.

Prolongation of longevity is a history-long desire of humans. Driven by the genetic contribution to longevity and the remarkable plasticity of healthy lifespan as demonstrated in animal models, arduous efforts have been directed to aging and longevity research over the years. Today, our understanding of lifespan determination is much greater than it was in the past, but administrable interventions for longevity enhancement are still virtually absent. The aim of this article is to highlight the technical gap between basic biogerontological research and intervention development, and to explore the importance of nucleic acid (NA) delivery technologies in bridging the gap. It is hoped that this article can engender more awareness of the roles of NA delivery technologies in biogerontological interventions, particularly NA therapy.

Food technology is a burgeoning field of applied science, invading many areas of the food industry and making contributions to economic advancement; however, little research has focused on ethical aspects in this field. This article attempts to fill this knowledge gap by revisiting the tainted milk event in China in 2008, followed by a detailed discussion of the application of food technology ethics in industrial contexts. Through the lesson learnt in the Chinese food industry, it is hoped that more global concerns on ethical issues in food technology will be raised, thereby creating a more humane food production industry.

Chitosan is a naturally occurring cationic mucopolysaccharide. It is generally biocompatible, biodegradable, mucoadhesive, non-immunogenic and non-toxic. Although chitosan is able to condense nucleic acids (NA) (both DNA and RNA) and protect them from nuclease degradation, its poor water solubility and low transfection efficacy have impeded its use as an NA carrier. In order to overcome such limitations, a multitude of strategies for chitosan modification and formulation have been proposed. In this article, we will first give a brief overview of the physical and biological properties of chitosan. Then, with a special focus on plasmid DNA delivery, we will have a detailed discussion of the latest advances in chitosan-mediated NA transfer. For future research, the following three important areas will be discussed: chitosan-mediated therapeutic small RNA transfer, structure–activity relationships (SAR) in chitosan vector design, and chitosan-mediated oral/nasal NA therapy.