Search

In the preceding two chapters, we have discussed how polymeric carriers can be designed and have presented how cyclodextrins can enhance the delivery performance of the carriers. With these as the foundation, in this chapter we will discuss how polymeric carriers can be combined with inorganic upconversion nanoparticles (UCNPs) for enhanced versatility. Compared to the conventional down-conversion fluorophores, UCNPs show distinct advantages for biomedical use (e.g., absence of photobleaching and photoblinking, and higher spatial resolution). These advantages enable UCNPs to be used for the development of a multifunctional delivery system that cannot only mediate genetic manipulation but can also function as a probe for imaging and tracking applications.

Human growth and development are controlled by genetic materials. Manipulation of intrinsic genetic mechanisms may, therefore, provide opportunities to intervene in the aging process. One possible strategy for genetic manipulation is to target mRNA. To regulate the cytoplasmic level of mRNA, precise control of the rates of RNA synthesis and degradation is required. This can be achieved by using RNAi, which is a mechanism of gene regulation conserved in plant cells and mammalian cells. SiRNA is one of the RNA duplexes that can mediate RNAi. Because the action of siRNA is highly specific and efficient, this technology has not only facilitated the elucidation of the roles of players involved in the aging network, but has also enabled the life span and the aging process to be modulated at the genetic level. In this chapter, we will highlight the opportunities and challenges of using RNAi for the design and development of biogerontological interventions.

Lifespan prolongation is a long-held desire of mankind. With technological advances, the mechanism of aging has been unraveled over the years. Along with an increase in understanding of the aging process, the development and execution of antiaging interventions are no longer mere concepts, but are getting closer to reality. To develop an intervention to tackle aging and age-associated ailments, the first step is to select a feasible approach by which the aging process can be modulated. The objective of this chapter is to introduce different theoretical frameworks for understanding the aging process, and to discuss their implications for the development of biogerontological interventions. These frameworks will likely constitute the conceptual foundation of antiaging therapies that will be designed by using the technologies which will be covered in subsequent chapters of this book.

Tissue engineering is the science of producing functional tissues to restore, maintain, or improve the function of damaged tissues. In practice, the use of a scaffold, which is generated from specific building materials, is often involved when tissue engineering is performed for tissue regeneration and repair. In this chapter, we will present an overview of strategies for the fabrication and modification of scaffolds, followed by a discussion of the use of engineering technologies in tissue regeneration. With the synopsis of major advances presented in this chapter, it is hoped that the possible use of tissue engineering can be illuminated for the future development of interventions for biogerontological applications.

Up till now we have discussed the design of various systems for genetic manipulation, and have highlighted the prospects of incorporating cyclodextrins and upconversion nanoparticles into the systems to enhance the versatility and functionality. Because this is the last chapter of Part II, we will switch our focus from nucleic acid transfer to delivery of nongenetic materials, particularly chemical drugs, and will present the advances in the development of hydrogel nanoparticles as drug carriers. Nanoparticles are submicronic colloidal systems with a high surface-to-volume ratio. The presence of a large surface area can enable surface functionalization, and can also enhance the adsorption of poorly soluble drugs. Together with their high biocompatibility, hydrogel nanoparticles are systems that warrant further exploration for biological applications and intervention development.

Animal genomes possess hundreds of miRNA molecules, with each of these molecules being able to regulate a network of broad, yet specific, gene targets. These molecules are, therefore, regulatory tools that can potentially serve as modulators of biological processes, such as aging. In fact, a growing body of evidence on age-associated changes in miRNA expression profiles has already been collected in models ranging from Caenorhabditis elegans to humans; however, until now, little discussion has been made in literature to exploit the feasibility and technical demands of turning the increasing knowledge of miRNA biology into antiaging therapies. In this chapter, we will provide a snapshot of the current understanding of the roles of miRNA in modulating the aging networks. Major chemical techniques, which are applicable to manipulate the structure of nucleic acid therapeutics and to develop delivery systems for intervention execution, will also be discussed for bench-to-clinic translation of miRNA-based antiaging interventions.

Over the years, different small-molecule compounds and agents (such as plasmids, proteins, and peptides) have been identified to modulate biological processes, and have paved the way possibly to interfere with the mechanisms of various physiological phenomena, such as aging. To make these agents effective and applicable to antiaging interventions, those agents have to be delivered to target sites for action. Advances in the design of delivery systems are, therefore a pivotal step in intervention development. In the previous chapter, we have introduced major theoretical frameworks for tackling aging. In this chapter, we will give an overview of the delivery technologies available at the moment for turning antiaging therapies from theory to practice.

Protein kinases are proteins that can chemically incorporate substrate proteins with phosphate groups. They play important roles in regulating different biological mechanisms, ranging from energy metabolism to cell cycle progression. As the synthesis and activity of proteins in the body are largely governed by gene expression in cells, modulation of the activity of protein kinases may thus be achieved simply by using genetic manipulation. In the last two chapters, we have discussed how genetic manipulation can be exercised by using small interfering RNA and microRNA. In this chapter, by taking protein kinases as an example, we will illustrate how manipulation of biological processes can be achieved at the protein level. Apart from delineating the roles played by protein kinases in aging, we will introduce different technologies for protein delivery, and will review recent advances in the design of stimuli-responsive polymeric systems for precise control of protein release. Finally, we will present how cell-penetrating peptides can be used for direct modification of proteins to enhance the delivery efficiency.

Aging is the major cause of death and medical costs; works on the development of biogerontological interventions, therefore, could bring about medical and financial benefits. As these works may lead to a venture into new territory, they have also caused concerns. For this, barriers to the development of a biogerontological intervention are no longer merely technical in nature. Ethical and social problems are needed to be addressed. In this chapter, we will revisit major ethical issues that are related to basic research, in vivo experimentation, and bench-to-clinic translation during the development of biogerontological interventions. Possible solutions to some ethical barriers will be highlighted to minimize the criticism and ethical concerns imposed to intervention development.

When we develop interventions to tackle aging, we do not only wish to postpone the age-associated physical death but also hope that our extended life is healthy, fruitful, and supportive. The concept of “antiaging,” therefore, contains both technical and socio-cultural meanings. As the final chapter, here we will delineate the relevance of social support to attaining the fullness of life span extension. In addition, we will discuss how the traditional rhetoric on aging, which has been regarded as only a normal stage of life rather than a disease by itself, has shaped the distribution of public funding to form a barrier to the development of biogerontological interventions. It is hoped that, by highlighting the social barriers to the success of intervention development, more awareness could be stimulated to establish a more supportive social and research environment for prolongation of both life span and health span in the future.

In the previous chapter, we have discussed the possible use of viral vectors for manipulation of the aging process at the genetic level, and have introduced representative strategies to engineer viral properties. Despite their high transduction efficiency, viruses are pathological entities. This leads to safety concerns, and has limited the widespread acceptance when viral vectors are to be used in humans. The development of nonviral gene delivery techniques has, therefore, attracted increasing research interests. Due to their high structural flexibility, polymers have emerged as one of the most extensively studied nonviral carriers. In this chapter, we will introduce major factors that shall be considered when designing polymeric vectors for genetic manipulation.

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.

Polymeric carriers have emerged as major non-viral alternatives for gene delivery due to their lower immunogenicity and pathogenicity. However, during intracellular delivery of these carriers, multiple barriers have to be overcome or the efficiency of gene delivery will be impeded. A thorough understanding of these cellular impediments is pivotal to optimizing the efficiency of polymer-based gene delivery. This review delineates the major barriers encountered during intracellular delivery of polyplexes and discusses possible molecular designs to overcome these barriers. Based on a review of the latest strategies to enhance the intracellular delivery process, we provide insights into the further development of polymeric carriers with enhanced efficiency in transfection.

Polyelectrolyte complexes formed between chitosan (CS) and anionic polymers have attracted increasing interest in drug delivery. In this study, CS is copolymerized with hypromellose via a coupling reagent-mediated approach to form a water-soluble, nontoxic CS derivative, namely hypromellose-graft-CS (HC), which is subsequently complexed with carboxymethylcellulose (CMC) to generate a polyampholytic hydrogel. When compared with conventional CS, HC is highly water-soluble across a wide pH range, and has a substantially higher pH buffering capacity to provide a pH-stable environment for delivery of drugs. In addition, the polyelectrolyte complex of HC exhibits a drug encapsulation efficiency of over 90% in all drugs tested, which is 1-2 fold higher than the efficiency attainable by the polyelectrolyte complex of conventional CS, with a 2-3 fold longer duration of sustained drug release. Our results indicate that as a novel polymer, HC has excellent promise for future pharmaceutical applications.

Polymers have a wide diversity of applications, ranging from therapeutics delivery to tissue engineering. While advances in polymer chemistry have facilitated synthesis and development of new polymers, increasing efforts have also been directed to engineer properties of existing polymers. One of the common approaches to modify polymer properties is cold drawing, which can align polymer chains and orient the chains in a crystalline manner. Regarding the industrial significance of cold drawing in polymer engineering, this study used semi-crystalline high density polyethylene (HDPE) as a model to examine the effect of cold drawing on the anisotropic mechanical properties of polymers. During cold drawing, the yield strength of the polymer was shown to be in a positive relationship with the strain rate, and the hardness of the cold-drawn region was demonstrated to be significantly enhanced. Our results confirmed the feasibility of engineering the properties of polymers by applying tension for plastic deformation, and highlighted the importance of precise control of the strain rate in the treatment.

Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides bearing a basket-shaped topology with an "inner-outer" amphiphilic character. The abundance of hydroxyl groups enables CDs to be functionalized with multiple targeting ligands and imaging elements. The imaging time, and the payload of different imaging elements, can be tuned by taking advantage of the commercial availability of CDs with different sizes of the cavity. This review aims to offer an outlook of the chemistry and engineering of CDs for the development of molecular probes. Complexation thermodynamics of CDs, and the corresponding implications for probe design, are also presented with examples demonstrating the structural and physiochemical roles played by CDs in the full ambit of molecular imaging. We hope that this review not only offers a synopsis of the current development of CD-based molecular probes, but can also facilitate translation of the incremental advancements from the laboratory to real biomedical applications by illuminating opportunities and challenges for future research.

Upconversion nanoparticles (UCNPs) represent an important topic in nanotechnology, and have extended possibilities in gene delivery beyond the reach of many existing technologies., Due to their large anti-Stokes shifts, sharp emission spectra and long excited-state lifetimes, upconversion nanoparticles (UCNPs) have attracted an increasing amount of research interests, and have shown great potential for enhancing the practical utility of gene therapy, whose versatility has been limited by existing gene delivery technologies that are basically mono-functional in nature. Despite this, up to now in-depth analysis of the development of UCNPs for gene delivery has been scant in the literature, even though there has been an upsurge of reviews on the chemistry of UCNPs and their applications in bioimaging and drug delivery. To fill this gap, this review aims to present the latest advances in the development and applications of UCNPs as gene carriers. Prior to describing the prominent works published in the field, a critical view on the properties, chemistry and molecular design of UCNPs for gene delivery is provided. With a synopsis of the recent advances in UCNP-mediated gene delivery, challenges and opportunities could be illuminated for clinical translation of works in this nascent field of research.

Herbal medicine, as an integral component of oriental medicine, has assimilated into the lives of Asian people for millennia. The therapeutic efficiency of herbal extracts and ingredients has, however, been limited by various factors, including the lack of targeting capacity and poor bioavailability. Hydrogels are hydrophilic polymer networks that can imbibe a substantial amount of fluids. They are biocompatible, and may enable sustained drug release. Hydrogels, therefore, have attracted widespread studies in pharmaceutical formulation. This article first reviews the latest progress in the development of hydrogel-based materials as carriers of herbal medicines, followed by a discussion of the relationships between hydrogel properties and carrier performance. Finally, the promising potential of using hydrogels to combine medicinal herbs with synthetic drugs in one single treatment will be highlighted as an avenue for future research.

Poly(ethylenimine) (PEI) is a cationic polymer extensively exploited for non-viral gene delivery; however, its wide application has been impeded by its cytotoxicity. PEI can assume either a branched or linear configuration. Whereas branched PEI (bPEI) is more chemically reactive and can form smaller complexes with DNA under salt-containing conditions, lPEI is generally less toxic and exhibits higher transfection efficiency. In this study, we cross-linked low-molecularweight lPEI with methyl β-cyclodextrin (MβCD) to form MβCD-lPEI (MLP). The structure of MLP was successfully characterized by NMR, FT-IR, MALDI-TOF and elemental analysis. In the standard serum-free transfection environment, MLP could effectively transfect glioblastoma, melanoma and hepatocarcinoma cells. A high transfection efficiency was maintained in the presence of serum. Apart from its high transfection efficiency, MLP was found to have negligible cytotoxicity over a wide range of concentrations and to exhibit a low membrane disruptive capacity ex vivo. MLP warrants further development as a promising gene delivery system for future research.

MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, and have displayed important roles in areas spanning from embryonic development to skin physiology. Despite this, till now little is known about the significance of miRNAs in cutaneous wound healing. In this mini-review, we discuss the existing evidence on the roles of miRNAs in physiological processes relevant to cutaneous wound healing, followed by a highlight of the prospects and challenges of future development of miRNA-based wound therapies. With existing technologies of nucleic acid transfer and miRNA modulation, it is anticipated that once the roles of miRNAs in wound healing have been clarified, there will be a vast new vista of opportunities brought up for development of miRNA-targeted therapies for wound care.

Runx3 is essential for normal vertebrate lung development and Runx3 knockout (KO) mice die within 24 h after birth because of various organ defects including defects in alveolar expansion. For proper early lung development, vasculogenesis and angiogenesis are necessary in humans. Previous studies have reported that various signaling molecules, such as CD31, VEGF and vWF, are closely related to lung vasculogenesis and angiogenesis. To confirm the relationship between Runx3-related lung defects and vasculogenesis, the localization of various blood vessel markers is examined in WT and Runx3 KO mouse lungs at PN1. Our results indicate that CD31, VEGF and vWF were dramatically up-regulated by a loss of Runx3 during lung development. Moreover, U0126, a MEK inhibitor, rescued the lung phenotype and vascularization by regulation of ERK signaling. Therefore, it was concluded that lung vasculogenesis and angiogenesis were induced in the Runx3 KO mouse, which shows lung defects, by increased CD31, VEGF and vWF.

Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides. They consist of (α-1,4)-linked glucose units, and possess a basket-shaped topology with an "inner-outer" amphiphilic character. Over the years, substantial efforts have been undertaken to investigate the possible use of CDs in drug delivery and controlled drug release, yet the potential of CDs in gene delivery has received comparatively less discussion in the literature. In this article, we will first discuss the properties of CDs for gene delivery, followed by a synopsis of the use of CDs in development and modification of non-viral gene carriers. Finally, areas that are noteworthy in CD-based gene delivery will be highlighted for future research. Due to the application prospects of CDs, it is anticipated that CDs will continue to emerge as an important tool for vector development, and will play significant roles in facilitating non-viral gene delivery in the forthcoming decades.

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.

Multidrug therapy may yield higher therapeutic effects as compared to monotherapy, yet its wide application has been hampered by the limitations of conventional drug delivery systems, in which not only incompatible drugs cannot be co-delivered but also the release rates of individual co-delivered drugs cannot be tuned separately. Regarding these limitations, we adopt the microfluidic electrospray technology to fabricate alginate-based multicompartment microgel beads. By using cadmium-telluride (CdTe) quantum dots (QDs) and a quenching agent as a model pair, the beads are shown to effectively separate incompatible drugs during co-delivery, and significantly prolong the time of observable fluorescence emission from QDs co-delivered with a quenching agent. Moreover, the drug release rates from different compartments can be tuned using the polymer blending technique to achieve a variety of drug release patterns. This study is one of the first to adopt the microfluidic electrospray technology to generate microgel beads with such versatility for co-delivery of multiple drugs. Our results provide evidence for the promising potential of our beads to be further developed as a carrier for multidrug therapy and other applications that require co-administration of multiple bioactive agents.

Proteins have emerged as an important class of therapeutic agents due to their high specificity in their physiological actions. Over the years, diverse protein carriers have been developed; however, some concerns, such as the relatively low loading efficiency and release sustainability, have limited the efficiency of protein delivery. This study reports the use of hydrogel nanoparticles based on a novel copolymer, poly(ethylenimine)-graft-polysorbate (PEIP), as effective protein carriers. The copolymer is fabricated by grafting poly(ethylenimine) (PEI) with polysorbate 20 using carbonyldiimidazole chemistry. Its cytotoxicity is much lower than that of unmodified PEI in RGC5 and HEK293 cells. In comparison with nanoparticles formed by unmodified PEI, our nanoparticles are not only more efficient in cellular internalization, as indicated by the 5- to 6-fold reduction in the time they take to cause 90% of cells to exhibit intracellular fluorescence, but also give a protein loading efficiency as high as 70-90%. These, together with the salt-responsiveness of the nanoparticles in protein release and the retention of the activity of the loaded protein, suggest that PEIP and its hydrogel nanoparticles warrant further development as protein carriers for therapeutic applications.

This study aims to modify a cyclodextrin-PEI-based polymer, PEI-β-CyD, with the TAT peptide for plasmid DNA delivery to placenta mesenchymal stem cells (PMSCs). By using the disulfide exchange between the SPDP-activated PEI-β-CyD and TAT peptide, the TAT-PEI-β-CyD polymer was fabricated and the success of this was confirmed by the presence of characteristic peaks for PEI (at δ 2.8-3.2 ppm), CyD (at δ 5.2, 3.8-4.0 and 3.4-3.6 ppm) and TAT (at δ 1.6-1.9 and 6.8-7.2 ppm) in the (1)H NMR spectrum of TAT-PEI-β-CyD. The polymer-plasmid-DNA polyplex could condense DNA at an N/P ratio of 7.0-8.0, and form nanoparticles with the size of 150.6±5.6 nm at its optimal N/P ratio (20/1). By examining the transfection efficiency and cytotoxicity of TAT-PEI-β-CyD, conjugation of the TAT peptide onto PEI-β-CyD was demonstrated to improve the transfection efficiency of PEI-β-CyD in PMSCs after 48 and 96 hours of post-transfection incubation. The viability of PEI-β-CyD-treated PMSCs was shown to be over 80% after 5 h of treatment and 24 h of post-treatment incubation. In summary, this study showed that the TAT-PEI-β-CyD polymer as a vector for plasmid DNA delivery to PMSCs and other cells warrants further investigations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12668-011-0010-9) contains supplementary material, which is available to authorized users.

Summary Nursing shortages are an international issue and are particularly evident in perioperative care, critical care and emergency services. The solution commonly adopted to tackle this problem is to increase the recruitment of nurses to replace the loss, whereas efforts to try and retain existing staff have only sporadically been mentioned. Furthermore, while retention programmes have occasionally received attention from some nursing scholars, they often fail to investigate the real needs of nurses. This article discusses three practical solutions adopted in Hong Kong, which could potentially alleviate difficulties with staff retention. It is hoped that the collaborative efforts of different professionals and nursing scholars will help to solve nursing shortages in the foreseeable future.

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.

This article is an autoethnographic portrait depicting my bereaved experience following the death of my maternal grandmother, which is my first memory related to the passing of a significant person. The objective of this portrait is not only to explore, with the first-person point of view, the profound experience of a child during such a critical period, but also to illuminate the grandmother-grandson relationship in a Chinese society. Readers are invited to tap into your emotional wealth, and feel my story by placing yourselves as a wounded storyteller (Frank, 1995). It is hoped that this article can provide you an insight into what would be psychologically needed by a child enduring the loss of a family member. The Rationale of Using Autoethnography Bereavement is a distressing experience in anticipating and adjusting to living after a significant relationship has been lost through death (Christ, Bonanno, Malkinson, & Rubin, 2002; Parkes & Weiss, 1983). It includes the internal adaptation of an individual, the mourning process, and alterations in external arrangements of one's living (Christ et al., 2002). Bereavement is a dynamic, rather than orderly and linear, process in which concurrent and overlapping reactions of an individual may recur at any time (Grossman, Clark, Gross, Halstead, & Pennington, 1995). During the process, individuals will experience grief with different intensity and duration, and discharge it through different means. In fact, grief and mourning are part of the healing process at that significant moment, enabling one to live with the reality of loss (Bowlby, 1980; Freud, 1957). Over the years, much effort has been paid to understand bereavement and resilience (d'Epinay, Cavalli, & Guillet, 2009; Paulsen, 2008; Pfund, 2005). For example, Barrera and colleagues (2007) have attempted to unveil the bereavement pattern of parents who lost a child to drowning and illnesses. Recently, Chapple & Ziebland (2010) also performed a qualitative study to understand the emotions of those bereaved in traumatic circumstances, and to explore how they decided whether or not to view the body of the deceased. Despite these endeavors, most of the present studies mainly focus on adults' perspectives. How the bereaved process is manifested in children has seldom been inquired. One of the few scholarly efforts to this is Grossman et al.'s (1995) paper in which sixteen prepubertal children and caretakers were interviewed to examine their grief, trauma, and behavior within 25 months of paternal suicide. Another example is Iglesias and Iglesias's (2005) research, which demonstrated that hypnotherapy could alleviate the symptomatology of childhood posttraumatic stress disorder (PTSD) caused by the traumatic loss of paternal figures and facilitate the spontaneous onset of the normal grief process among pediatric PTSD patients. No doubt, these works have furthered our understanding of various reactions exhibited during childhood bereavement (Irizarry, 1992). However, these studies were either on children of parental death (Grossman et al., 1995), which is an unusual traumatic death in the child's context, or on those undertaking psychotherapy during the course of the study (Furman, 1974; Iglesias & Iglesias, 2005; Irizarry, 1992; Kliman, 1977; Van Eerdewegh, Bieri, Parrilla, & Clayton, 1982). Attempts have seldom been made to research on the emotional tension borne by children following a more typical bereavement situation, such as grandparental death. Further, bereavement is a painful life event from which few people are spared. It is not simply a research object that could be understood just by disembodying it on the bench apathetically. It is a manifestation of connectedness between humans, and an emotional process desiring empathy from us as living beings. Unfortunately, until now studies on bereavement have been confined mainly to the traditional logical-scientific mode of knowledge (Bruner, 1986), in which the investigators as totally detached strangers rely solely on realist forms of representation (Hayano, 1979; Sparkes, 1995; Van Maanen, 1988). …

Microfluidics is a compelling technology that shows considerable promise in applications ranging from gene expression profiling to cell-based assays. Owing to its capacity to enable generation of single droplets and multiple droplet arrays with precisely controlled composition and a narrow size distribution, recently microfluidics has been exploited for delivery of genes. This article provides an overview of recent advances in microfluidic gene delivery, and speculates the prospects for further research. The objectives of this article are to illustrate the potential roles played by microfluidics in gene delivery research, and to shed new light on strategies to enhance the efficiency of gene therapy.

Successful gene therapy necessitates safe and efficient gene transfer. This article describes the use of a cationic polymer, which was synthesized by cross-linking low molecular weight branched poly(ethylenimine) (PEI) with both β-cyclodextrin and propane-1,2,3-triol, for efficient and safe non-viral gene delivery. Experimentation demonstrated that the polymer had a pH buffering capacity and DNA condensing ability comparable to those of PEI 25 kDa. In B16-F0 cells, the polymer increased the transfection efficiency of naked DNA by 700-fold and yielded better transfection efficiencies than Fugene HD (threefold higher) and PEI 25 kDa (fivefold higher). The high transfection efficiency of the polymer was not affected by the presence of serum during transfection. In addition to B16-F0 cells, the polymer enabled efficient transfection of HepG2 and U87 cells with low cytotoxicity. Our results indicated that our polymer is a safe and efficient transfection reagent that warrants further development for in vitro, in vivo and clinical applications.

Use of ceramics and polymers continues to dominate clinical procedures in modern dentistry. Polymers have provided the basis for adhesives, tissue void fillers, and artificial replacements for whole teeth. They have been remarkably effective in the clinic at restoration of major dental functions after damage or loss of teeth. With the rapid development of polymer science, dental materials science has significantly lagged behind in harnessing these advanced polymer products. What they offer is new and unique properties superior to traditional polymers and crucially a range of properties that more closely match natural biomaterials. Therefore, we should pursue more vigorously the benefits of advanced polymers in dentistry. In this review, we highlight how the latest generation of advanced polymers will enhance the application of materials in the dental clinic using numerous promising examples. Polymers have a broad range of applications in modern dentistry. Some major applications are to construct frameworks that mimic the precise structure of tissues, to restore tooth organ function, and to deliver bioactive agents to influence cell behavior from the inside. The future of polymers in dentistry must include all these new enhancements to increase biological and clinical effectiveness beyond what can be achieved with traditional biomaterials.