Abstract

Cancer vaccines based on tumor cell components have shown promising results in animal and clinical studies. The vaccine system contains abundant tumor antigen components, which can activate the immune system by antigens. However, their efficacy has been limited by the inability of antigens delivery, which are the core components of vaccines, further fail to be presented and activation of effective cells. Nanotechnology offers a novel platform to enhance the immunogenicity of tumor-associated antigens and deliver them to antigen-presenting cells (APCs) more efficiently. In addition, nanotreatment of tumor cells derivate active ingredients could also help improve the effectiveness of cancer vaccines. In this review, we summarize recent advances in the development of cancer vaccines by the combination of nanotechnology and tumor-based ingredients, including liposomes, polymeric nanoparticles, metallic nanoparticles, virus-like particles and tumor cells membrane, tumor lysate, and specific tumor antigens. These nanovaccines have been designed to increase antigen uptake, prolong antigen presentation, and modulate immune responses through codelivery of immunostimulatory agents. We also further discuss challenges and opportunities in the clinical translation of these nanovaccines.

Introduction

Cancer immunotherapy has revolutionized cancer treatment by harnessing the immune system to recognize and attack cancer cells [1–3]. Among various immunotherapeutic approaches, cancer vaccines have attracted significant attention due to their potential to induce long-lasting and specific immune responses against tumor cells [4–7]. By comparison with surgery, it hardly produce large wounds, nor does it cause higher toxicity in normal tissues and drug tolerance like chemotherapy in the treatment of tumor. However, the clinical efficacy of cancer vaccines based on tumor cell components, such as peptides and proteins, is limited by their poor immunogenicity and inefficient delivery to antigen presentation cells (APCs). Although, many cancer vaccines were applied with the immune-stimulatory agents, such as the programmed cell death protein 1 (PD-1), CpG oligonucleotide, etc. The clinical response rates remain low, especially in the hypoimmunogenic tumors. As we all know, pancreatic cancer is a more difficult type for immunotherapy as a low immunogenic tumor. Therefore, there are few effective cancer vaccines that can actively promote the pancreatic cancer treatment. Meanwhile, limited by the specific tumor antigens, the development of cancer vaccines was extremely difficult.

The field of cancer vaccines has seen significant advancements in recent years, with numerous studies focusing on different aspects of vaccine development and application [8–12]. These advances have been facilitated by the exploration of various types of cancer vaccines, including those targeting viral antigens, neoantigens, and other tumor-specific antigens [13–16]. One approach in cancer vaccine research involves targeting shared antigens from viral infections linked to certain cancer types, such as Epstein–Barr virus and HPV. Studies have shown promising results with vaccines targeting viral antigens like Epstein–Barr nuclear antigen 1 and latent membrane proteins, as well as HPV-related antigens, demonstrating favorable antitumor efficacy and the potential to establish durable T cell memory in rapidly progressing HPV-positive tumors [17]. Another significant area of research is neoantigen cancer vaccines. Neoantigens, derived from nonsynonymous cell variants, are only expressed in tumor cells and can bypass thymus-negative selection, leading to robust neoantigen-specific T cell responses [14]. Advances in genomic and transcriptional profiling have made identifying putative neoantigens possible, although challenges remain in predicting which neoantigens can effectively induce neoantigen-specific T cell responses [18–20]. Cancer vaccines are being developed to stimulate antitumor immunity with tumor antigens delivered in various forms, such as cells, peptides, viruses, and nucleic acids [21–24]. These vaccines aim to overcome tumor heterogeneity and reverse the immunosuppressive microenvironment. Challenges in the field include single antigen targeting, weak immunogenicity, off-target effects, and impaired immune response [25–27]. Current research and reviews provide insights into the principle of action, components, classification, delivery methods, and progress of cancer vaccines, offering a broader perspective for future vaccine design.

Recent studies have shown that tumor antigens can be used for the design of cancer vaccines without the necessity to identify, parse, and reconstruct certain antigens [28–31]. A novel concept has been proposed that the whole antigen vaccine systems derived from tumor cells could be designed to conquer cancer treatments [32–34]. The tumor cells themselves are a huge antigen pool with countless tumor antigen epitopes, which can be used to activate antitumor immune response. Among them, more studies have focused on the application of tumor cell membrane as tumor antigens to stimulate APCs and further activate the antitumor immune response of T cells. In addition, the activation of T cells in immune response requires the involvement of costimulatory molecules. Some studies are based on this theoretical foundation, using genetic engineering to modify tumor cell membranes. By retaining antigen on the cell membrane and inducing the expression of costimulatory molecule CD80, T cells can be directly activated, thereby achieving antitumor immune response [35] (Figure 1). Of course, many studies combine tumor cell membranes that retain tumor antigens with other functional molecules to directly activate dendritic cells (DCs) for antigen presentation, leading to the activation of T cell immune response. These are two different approaches aimed at achieving the same goal [36–38]. A series of nanovaccines developed on this basis have been widely used in the treatment of different tumor cells and preclinical experiments.

Abstract

Introduction

Materials and methods

DPPH

Microbial studies

Result and discussion

Microbial studies

Conclusion

Acknowledgements

References

Abstract

     Nanotechnology involving biopolymers is comprehensively used in biomedical applications, planning sciences, and food development. The present work describes the synthesis, characterization, and application of carrageenan and zinc oxide nanoparticles (ZnONPs) based hydrogel. The synthesized hydrogels were subsequently characterized using FTIR, XRD, SEM, and TG-DTA. The swelling property, antioxidant activity, and whole blood clotting effectiveness of the Carrageenan hydrogel, and Carrageenan Hydrogels Impregnated with Zinc Oxide Nanoparticles were evaluated. The Carrageenan + ZnONPs (C/ZnONPs) hydrogels showed good antioxidant, and blood clotting activity than the pure carrageenan hydrogel. In addition, the stable C/ZnONPs hydrogels exhibit good antimicrobial activities against both Gram-negative and Gram-positive bacterial strains. Biofilm analysis showed that C/ZnONPs hydrogels have excellent anti-biofilm potential in both inhibition and disruption of preformed biofilm. The obtained results suggested that the carrageenan and Zinc oxide nanoparticles based hydrogel have promising biological applications.

Introduction

     Pathogenic microorganism resistance to frequently used antibiotic substances have become an important health concern in the 21st century. The development of microorganism resistance to antibiotics has significantly increased morbidity and mortality, longer hospitalization and increased health care costs.[1] Resistance is increasing against antibiotics, particularly to the first line, inexpensive, and broad-spectrum antibiotics, but also to the newly developed antibiotics; since the development of novel alternative is necessary.[2,3]

In the specific case of wound management there are several reports of the microorganism resistance to the drug used to manage wounds.[4] The role of microbial infections in the development of wound infections is well established, the life threatening nature of the wound infections has maximized its importance in human health. In addition, the cost of medication for wound management is also high.[5,6] Hence the exploration of new substance for the wound management is very important.

Conclusion

     The synthesized C/ZnONPs hydrogels was produced by a simple and efficient method, performing proper swelling capacity and much better mechanical properties. It exhibited better antioxidant, blood clotting activity and also possess excellent antibacterial and biofilm efficacy against B. subtilis, S. aureus, E. coli and K. pneumonia. The present study confirmed that C/ZnONPs hydrogel have multi-potential property. Thus, the present study suggests that this bio-reduction practice is a well suitable system for large-scale production. The blood clotting and biofilm efficacy were tested in this study only at the grassroot stage which needs to be addressed further.

Abstract

Introduction

Polyacrylamide hydrogels and their polymerization

Polyacrylamide hydrogel in cell biology and drug delivery system

Classification of hydrogels: a broad overview

Homo-polymeric hydrogels

Co-polymer hydrogels

Semi-interpenetrating network

Interpenetrating network

Recent progress (2019–2022) of polyacrylamide-based hydrogel composites

Swelling and degradation behaviour of PAM hydrogels

Mechanical properties of PAM hydrogel composites

Tribological and rheological properties of PAM composites

Magnetic hydrogel composites

Biological properties of the PAM hydrogel composites

Applications of polyacrylamide hydrogels

Conclusions

Scope for the future work

Acknowledgements

References

Abstract

     Polyacrylamide hydrogels have made an immensely important place in various fields having bio-compatibility, high water-holding capacity, tunability and cheap synthesis, which has attracted researchers’ attention. Polyacrylamide can be chemically infused with other elements or compounds to find applications in magnetic biosensors, drug delivery, cartilage repair and wound dressing. This paper throws light on the brief introduction of hydrogels and their classification. The polymerization method of polyacrylamide hydrogel followed by its clinical uses (cell biology and drug delivery) is adorned in the report. Keeping at the centre, the recent highlights on the research work done on polyacrylamide hydrogel composites using various reinforcing additives are crucially explored first time in the present report. The improvement practice in the strength, bonding and self-healing of the polyacrylamide hydrogel is demonstrated by the encapsulation of nanoparticles like silicon, carbon nanotubes, gelatine, cellulose, etc. The clinical aspects of the polyacrylamide are corroborated by the cell viability, proliferation and migration. Thus, polyacrylamide hydrogels are emerging candidates, precisely illuminated in the review, which can be an influential highlight designed for upcoming research.

Introduction

     Hydrogels are flexible polymers with excellent biocompatibility. Due to their three-dimensional network, hydrogels have high water-holding capacity. Further, hydrogels have the ability to form blends by using more than one monomers and cross-linkers. Chemical infusion of hydrogels has also been tested with several biocompatible materials. These hydrogel composites are tested for a ‘new generational’ changes in existing applications. This infusion using corresponding salts followed by reduction using a suitable reducing agent forms nanoparticles suspended in the hydrogel. Research in magnetic bio-sensing materials has tested hydrogels infused with magnetic nanoparticles also called ferrogels. For applications like cartilage replacement as well, hydrogel-based composites are carefully prepared for specific cartilage-like properties [1, 2]. Gels are formed when crosslinker forms bonds laterally linking two polymeric chains. This is much like the two sugar phosphate DNA backbones that are joined by chromosome pairs. Except that, the polymeric chains are flexible, unlike DNA backbones! Without cross-linking, the polymeric chains will dissolve into the aqueous phase and only interaction between the chains is through a physical bond. Cross-linking also decides the strength-related properties of the gel. Optimizing the cross-linking method and the cross-linking ratio is essential for strength-related properties.

Conclusions

     Polyacrylamide hydrogels are emerging polymers due to their unique properties, which have made them useful in fields like cartilage repair, wound dressing, contact lenses, drug delivery and biosensors. The PAM hydrogel can be prepared by a monomer unit along with a cross-linker mixed in a suitable quantity. The PAM composites were fabricated by introducing some nanoparticles and reducing them to change these cations/anions into metal ions. The present review described the introduction of hydrogels with their different types, based on the polymeric network structure. The PAM hydrogels along with different nanoparticles like TiO2 and CNTs are turned with high strength ([ 0.43 and 2.340 MPa compressive strength and elastic modulus, respectively) composites. However, the puncture resistant of the PAM was also enhanced with these nanoparticles, estimated using the needle insertion technique. The tribological and magnetic investigations (magnetic saturation 1.41 emu/g) revealed an improved performance of PAM with encapsulation of nanoparticles due to the fine-grained structure and lubrication effects (created by CNTs). Furthermore, the biological activity of PAM composites was remarkably important and ideal for the implementation in biomedical research. Thus, in short, this review report is an important highlight for PAM hydrogel composites and can provide a prominent direction to future research based on the PAM hydrogels for biomedical applications.

Abstract

Introduction

Materials and methods

Characterizations

Results and discussion

Optimized reaction conditions

FTIR spectra analysis

SEM–EDS analysis

XRD analysis

TGA analysis

Conclusion

Declarations

References

Abstract

     An interpenetrating polymer network (IPN) containing gum acacia (GA), poly(methacrylic acid) (MAA), and poly(acrylic acid) (AA) was developed using a two-step aqueous polymerization method. Firstly, semi-IPNs were produced by radical polymerization of MAA chains onto GA in the presence of ammonium persulfate as a free radical initiator and N, N′-methylene-bisacrylamide (MBA) as a cross-linking agent using a microwave heating. To obtain a semi-IPN with a higher swelling percentage, several reaction parameters such as initiator, monomer, and crosslinker concentrations were varied. The percentage swelling (%S) was highly dependent upon the reaction conditions. The optimal reaction conditions for maximal %S were 2.55 × 10–2 mol/L initiator concentration, 12 mL solvent, 0.424 × 10–3 mol/L of monomer, and 2.16 × 10–2 mol/L cross-linker concentration, according to the findings. GA-g-poly(MAA) was the name to given to the semi-IPN. Second, IPN was created by grafting AA chains onto a GA-g-poly(MAA) matrix that had been optimized. The IPN was named as a GA-g-poly(MAA-IPN-AA). The reduction of silver ions to silver nanoparticles (AgNPs) was carried out by heating the mixture of flower extract of Koelreuteria apiculate under microwave radiation.

Introduction

     Hydrogels are three-dimensional (3D) networks formed by the crosslinking of hydrophilic polymers [1, 2]. They might swell while maintaining their network structure by absorbing signifcant amounts of water or biological fluids. The inclusion of hydrophilic groups such as -OH, -CONH, -CONH2, -COOH, and -SO3H along the polymer chain contributes to their ability to absorb a large amount of water [1]. Polysaccharide hydrogel networks have received a lot of attention in recent years [3–5]. The physico-chemical properties of these hydrogels frequently differ significantly from those of the macromolecular constituents. Hydrogel characteristics can also be altered utilizing a range of physical and chemical crosslinking techniques [3, 6]. Various researchers have examined a number of polymeric systems to create hydrogels [7]. The polymer composition can be classified as natural polymeric hydrogels, synthetic polymer hydrogels, and or a combination of both [7]. Because of their non-toxicity, low cost, permeability, and biocompatibility, hydrogels have gotten a lot of attention in a variety of sectors [8–10].

Conclusion

     Antimicrobial materials have been studied extensively in response to rising microbial resistance to traditional antibiotics and disinfectants. Natural polysaccharidebased hydrogels and their composites containing metal nanoparticles could be suitable for antibacterial applications in some cases. Using a microwave irradiation approach, we were able to successfully synthesis GA-gpoly(MAA) and GA-g-poly(MAA-IPN-AA) based hydrogels from GA. APS and MBA being used as initiator and cross-linker, respectively. To achieve maximum %S of semi-IPN (588%) and IPN (500%), diferent parameters were optimized. The formation of cross-linked hydrogels and hydrogel composites with AgNPs was successfully demonstrated using FTIR analysis. The SEM investigation of hydrogel networks reveals a variety of morphologies, which could be attributed to structural diferences between semi-IPN, IPN, and their composites with AgNPs. SemiIPN, IPN and their composite showed superb antibacterial potential against E. coli, M. luteus, P. aeruginosa, Rihzobium species, and S. aureus, and may be used to treat a variety of infected efuents. Such interconnected hydrogels will give superior material properties, particularly in biomedical research, to prevent biomaterialassociated infections as well as general pathogenic invasions into the body. The synthesized hydrogel samples will lead to enhanced applications in the future, as well as a deeper knowledge of material interactions. The eforts to improve the property profle of cross-linked hydrogels are still on, with the hope of improving overall performance in terms of water uptake capacity, biocompatibility, and biodegradability.

Abstract

1. Introduction

2. Experimental section

3. Result

4. Discussion

5. Conclusion

Declaration of competing interest

Acknowledgements

References

Abstract

     Hydrogel is a nature scaffold that can degraded in animal body and can be used as a drug delivery system, we hypothesized that patch made of three layers of hydrogel with different PLGA nanoparticle drugs (bio-patch) can be used to decrease venous neointimal hyperplasia. Rat inferior vena cava (IVC) patch venoplasty model was used. Samples from rat IVC direct suture (DS), decellularized thoracic artery patch (TA) venoplasty and bovine pericardial patch (BPP) venoplasty were examined at day 14 after implantation. Sodium alginate and hyaluronic acid (SA/HA) hydrogel was used, three layers hydrogel patch (control) and three layers hydrogel patch with PLGA nanoparticle drugs (bio-patch) were used in rat IVC venoplasty. Patches were harvested at day 14 and analyzed. In rats, TA and BPP patch showed a thicker neointima and adventitia compared to the DS, there were larger numbers of CD68 and PCNA positive cells in both groups. The control hydrogel patch showed much thinner neointima and adventitia compared to TA and BPP patches. In both of the neointima and peri-patch area, bio-patch showed significantly fewer smooth muscle cells, fewer CD68, fewer PCNA positive cells, fewer collagen-1 positive cells, fewer p-smad2 positive cells, fewer TNF-α positive cells compared to control hydrogel patch. Bio-patch made of hydrogel and PLGA nanoparticle drugs showed a thinner neointimal thickness, and is biocompatible to the animal body.

Introduction

     Prosthetic vascular grafts like Dacron and expanded poly tetra fluoroethylene (ePTFE) have a lower patency rate in peripheral bypass surgeries [1,2]. Both grafts showed poor long-term patency rate when the diameter is smaller than 6 ​mm [3]. In addition, biological graft like cryopreserved allografts, bovine or porcine pericardium, are also commonly developed as vascular grafts [[4], [5], [6]]. However, these materials have a risk of infection, foreign body reaction as non-autologous materials, meanwhile they cannot be absorbed by the body, which limit their application [7]. Along with the advancement of material science and technologies, various of novel materials are emerging and under investigation in vascular surgery [[8], [9], [10]]. Decellularized fish swim bladder also showed potential application as tube and patch grafts [3], plant leaf can also be used a patch to repair rat inferior vena cava (IVC) [11,12]. Great progress has been made in the field of vascular patches recently, however, the big challenge of neointima formation still not be solved [13,14].

Conclusion

     In conclusion, we showed a novel idea to fabricate a three layers vascular patch with different PLGA nanoparticle drugs (bio-patch), this bio-patch can effectively decrease neointimal hyperplasia in a rat IVC venoplasty model; this research showed that the bio-patch may be a potential substitute of other prosthetic patches in vascular surgery.

Abstract

     Magnetic nanoparticles (MNPs) represent an advanced tool in the medical field because they can be modified according to biomedical approaches and guided by an external magnetic field in the human body. The first objective of this review is to exemplify some promising applications in the medical field, including smart drug-delivery systems, therapies against cancer cells, radiotherapy, improvements in diagnostics using magnetic resonance imaging (MRI), and tissue engineering. Complementarily, the second objective is to illustrate the mechanisms of action and theoretical foundations related to magnetoresponsive materials.

Introduction

     Magnetic nanoparticles (MNPs) are nanoscale particles (1–100 nm) that can be guided through an external magnetic field due to their superparamagnetic, ferrimagnetic, and ferromagnetic properties, which may provide features for biomedical applications. MNPs with superparamagnetic properties are of special interest because they exhibit strong magnetic interactions under an external magnetic field, which disappear once the external magnetic field is removed. This property allows for the design of ferrofluids, since MNPs can be stabilized in solutions because they do not present magnetic interactions when the external magnetic field is switched off; and allows for in vivo performance, as in (i) cell marking [1], (ii) drug systems guided by a magnetic field [2], (iii) image contrast agents [3], and (iv) as heat generators in hyperthermia treatments [4].

     MNPs generally contains two main parts: the core and the coating. The core presents a predominant quantum effect, which commonly incorporates magnetic elements such as Fe, Ni, or Co as well as their corresponding oxides, while the coating is responsible for stabilizing and protecting the core from the chemical effects of the medium [5]. The coating also plays an essential role since it provides specific properties and functions to the nucleus; for example, biocompatible natural polymers, such as chitosan or cellulose, work as cargo vectors of therapeutic agents to release in a controlled manner (Figure 1). Due to these characteristics, biomedical device synthesis has shown great interest in low toxic superparamagnetic MNPs, to avoid embolization or other secondary effects for the patient at the molecular or cellular level [6].

Conclusions

     MNPs, in combination with superconducting magnets, have begun to play an essential role in advances in areas such as MDDS, MRI, and hyperthermia, among other fields. Therefore, it is crucial to continue the synthesis of MNPs and de

Abstract

     Wastewater from pharmaceutical industries contains different antibiotics and other effluents that directly affect the environment. For the degradation of antibiotics, nanotechnology is an emerging field in research that majorly focuses on molecules and atoms. Nanoparticles are fine micro-particles with more than one dimension from a size of 1–100 nm. The synthesized nanoparticles can directly be used for the process of degradation of antibiotics in wastewater. Titanium dioxide nanoparticles are majorly used among nanoparticles due to their small surface area and particle size. There are various physical, chemical and conventional (biological) methods for synthesizing titanium dioxide nanoparticles. Green synthesis is an environmentally friendly, less expensive and harmless approach, and these methods are much more efficient than any other physical-chemical means. Titanium dioxide nanoparticles are used for different purposes. In food products, these nanoparticles act as photocatalysts and are also used as a coating material in food packaging. Electrochemical biosensors are combined with titanium dioxide nanoparticles for developing nano sheet matrices. Furthermore, this review describes the usage of biological components (plants, microorganisms like fungi and bacteria) to synthesize titanium dioxide nanoparticles. The present review also focuses on applying synthesized titanium dioxide nanoparticles in various drug delivery systems and other bioactivities.

Introduction

     Water is one of the important components of life used in the domestic, industrial, and agricultural sectors. The increase in consumption leads to an increase in the toxicity of pollutants inside water. The concentrations of emerging pollutants like pharmaceutical compounds have increased [1]. Various types of pharmaceutical compounds are observed in the aqueous environment, including antibiotics. These compounds reach the aquatic habitat through hospital effluents, the pharmaceutical industry and human livestock. The consumption of antibiotics has increased, and the concentration increases inside the aquatic environment, leading to the development of antibiotic-resistant bacteria [2,3].

     To remove antibiotics from wastewater, the traditional sewage treatment method is not appropriate and is not much effective in removing the residuals of antibiotics. Nanoparticles can be used as a photocatalyst for the degradation of antibiotics and other organic pollutants [4]. Nanotechnology is defined as synthesizing and developing various nanomaterials by manipulating the matter at the nanoscale [5]. Nanomaterials are a bridge between molecular material and bulk material. They have a size range of 1–100 nm due to their different shapes, sizes, large surface area, and possess high reactivity [6]. This has become an emerging field in science in the last few years due to its wide range of applications [7]. Because of its small size, the effect can be seen in the physical, optical, chemical properties, melting point, and dielectric constant of various nanoparticles [8].

Conclusion

     The interest in green synthesis is due to its advantages of being innocuous to the environment. Different parts of plants are used for synthesis purposes, and their characterization using various techniques helps form TiO2 NPs of varied shapes and sizes. The green synthesis of TiO2 NPs can be used in biomedical, and the delivery of drugs and antibiotics in wastewater of pharmaceutical industries can be degraded using nanoparticles. Because of the less use of precursors, TiO2 is widely used to remove microbes from water surfaces. The nanoparticles inhibit the growth of microbes and are used in wound dressing. Moreover, nanoparticles synthesized using the green routes are more effective than chemical or physical means.

Abstract

Keywords

References

Abstract

New technologies emerge almost every day and they change how organizations and even governments operate. One of the technologies which had a great impact on business models is the cloud computing technology. Cloud computing impacts how resources and capabilities can be used to function effectively and efficiently. It allows organizations to operate in a competitive environment without focusing on scaling, maintenance, and failure. It became a key factor in IT vendors’ strategies and governments like US Apps, and The Kasumigaseki Cloud in Japan. This study will investigate the challenges for deploying cloud computing in the eHealth Context within developing countries. It will examine the doctors’ and managers’ evaluation of cost, security, infrastructure, management support and the importance of other challenges in deploying cloud computing in eHealth.

1. Introduction

Although technology has been a powerful tool for poverty reduction and improved standards of living in developing countries, the benefits have not been evenly distributed across the globe. Therefore, a great potential lies in the transfer of technologies to those areas that are still yet to benefit from such innovations and technological progress [1] . Thus, studying the cloud computing implementation in Egypt as a developing country can be of great help to the modernization of eHealth sector in the developing countries. Besides, they can cope with the west and enhance the availability of health care services with lower costs.

Developing countries lack resources, infrastructure and different elements of successful implementation of new technologies. Kshetri (2010) and Greenberg (2008) attested that Cloud computing allows access to advanced IT infrastructure, data centers [2], and application program that most development land do not have. Although, productivity can be enhanced through technology, developing countries, haven’t yet realized the potency and welfare of technology unlike the developed countries. Access to timely and appropriate technology pose a serious problem for the developing countries [1].Cloud computing presents a great benefit for developing countries for modernization through advanced technology with low initial investing that meet the capabilities and resources of developing countries. If the developing countries didn’t take advantage of such new technologies like the cloud , they would be excluded from world markets [1]. Cloud computing can be used to modernize the eHealth sector in Egypt as a developing country and hence enhance the healthcare service delivery. Hospitals will be able to use the cloud as a public utility through pay per use model . Arguably, organizations seeking cloud adoption may be worried about different aspects of the cloud implementation. These aspects include security, toll , legal compliance as well as change and jeopardy management. The paper is organized as follows; it begins by reviewing the literature of cloud computing. A qualitative approach is adopted to investigate the challenges of cloud implementation in eHealth from different perspectives; IT experts and doctors. Themes were identified using the critical instance technique. Finally, results are discussed and future work is recommended.

Abstract

Keywords

1. Introduction

2. MFNPs-based magnetoresponsive effects for biomedical applications

3. Conclusion and perspectives

Declaration of competing interest

Acknowledgments

References

Abstract

One of the most attractive features of magnetic ferrite nanoparticles (MFNPs) in biomedical application is that they can mediate external magnetic field to produce local magnetic field, magnetic thermal and magnetic force effects. These generated effects can later be utilized in the diagnosis and treatment of various diseases. The application performance is mainly determined by the nano-magnetism of MFNPs. Therefore, by modulating the magnetic properties, the improved magnetic resonance (MR) signals, magnetothermal, and magnetomechanical effects of the MFNPs can be achieved. In this review, we summarize the strategies used in the engineering of MFNPs to enhance MR imaging sensitivity and magnetic thermal conversion efficiencies. We will also discuss the detailed magnetoresponsive mechanism arising from the critical magnetic properties of MFNPs. Furthermore, we will highlight the recent progresses of the engineered MFNPs in biomedical applications, with emphasis in MR signal amplification, magnetothermal, and magnetomechanical response in biomedical applications.

1. Introduction

Since ancient Greek time, lodestone, i.e., bulk magnetite (Fe3O4), has been used in the treatment of common ailments. With the advancement in nano-biotechnology, the applications of such magnetic ferrite nanoparticles (MFNPs) have evolved, which extends to the modern biomedicine and clinical study [[1], [2], [3], [4], [5], [6], [7]]. As biological tissues are transparent to magnetic fields, the most attractive advantage of MFNPs in biomedical applications is that they can complete various functions triggered by invisible, tissue-penetrating magnetic field [8,9]. For instance, natural magnetotactic bacteria build iron oxide nanoparticles (IONPs) in a chain configuration to generate a permanent dipole in their cells so as to navigate toward their favorable habitats by sensing the Earth’s magnetic field [10]. These MFNPs possess good biocompatibility, which have already been used as imaging and therapeutic agents in preclinical and clinical settings [2,3,11]. As a result of the excellent magnetoresponsive properties of MFNPs, numerous exciting in vivo biomedical applications are created. These include imaging for non-invasive diagnosis of diseases [12], treatment of diseases with hyperthermia [13], magnetically driven nanorobots [14], magnetic activation of ion channel for cell signaling [15], manipulation of cell’s function and fate [16,17], and so on. Despite the good establishment of these concepts, there is a significant challenge in obtaining effective MFNPs that can achieve full functionality via the efficient conversion of the external energy of magnetic field. As such, due to their poor conversion ability, this greatly hinders their transition from bench to bed.

Highlights

Abstract

Keywords

1. Introduction

2. Materials and methods

3. Results

4. Discussion

5. Conclusions

Declaration of Competing Interest

Acknowledgement

References

Abstract

The objective of this research is to study the feasibility using nanomaterials to prevent and/or repair wear of teeth. Canine teeth have thin enamel prone to dental wear, causing pain, tooth loss, and infection. This research developed a new teeth repair agent based on the tribochemically active nanoparticles. The presence and properties of synthesized repair agents were evaluated after applying the repair agents by rubbing (simulated chewing) between extracted dog teeth. Polyether modified alpha‑zirconium phosphate (α-ZrP) nanoparticles form a strong and durable protective layer on a canine tooth’s enamel surface through chewing. The effectiveness of this protective film generation was enhanced by adding hydroxyapatite (HAp) nanoparticles into the repair agent. This protective film is up to 2 μm thick and has a hardness comparable to the enamel substrate. These results show that by chewing with the repair agent, the teeth are protected. The tomography result shows this repair agent also has the potential to mend cracks on the enamel surface. This research reports a novel approach to protect the wear of teeth. Nanoparticles promoted the generation of a protective film in situ during the chewing process. This nanomaterial can be the base of novel dental protective devices such as chewing toys or gums that preventing or reversing tooth wear and reducing the stress and cost of dental restoration operations.

1. Introduction
Tooth enamel is the hardest and most dense structure in the mammalian body. It serves to protect the interior of the tooth from the normal flora of the oral cavity and other harmful substances [1,2]. Although it is the hardest tissue in humans and animals [3–6], it can suffer damage from mechanical forces [7–12] and acidic solutions [13–16]. In dogs, the enamel layer is significantly thinner than in humans [17] and more prone to excessive wear and damage. This type of wear can result in dentin and pulp exposure causing significant oral pain, tooth loss, or periarticular and pulpal infections [18,19], leading to deterioration in quality of life and, in extreme cases, to be life threatening [13,20,21]. Recently, remineralization of damaged tooth enamel was presented as an alternative method to traditional dental operations [22–24]. These researchers utilized the bio-mineralization process that naturally presented in the dental environment [25–27]. Precursors to the nanoparticle hydroxyapatite were used to form the hard enamel tissue in vitro or in vivo [23,27]. Some examples of the precursors are casein phosphopeptide-stabilized amorphous calcium phosphate [28–30]; amelogenin with fluoride [31], and polydopamine with hydroxyapatite (HAP) [23]. Unlike traditional dental treatments, this method repaired teeth with materials that were almost identical to the teeth themselves. However, like the natural biomineralization process, using the remineralization method required significant time (>24 h) to take effect [22,23,27]. This is a major limitation to the clinical application of this approach.

1- Introduction

2- Experimental section

3- Results and discussion

4- Conclusions

References

Abstract

In this paper, a targeting hyaluronic acid (HA)/mesoporous silica nanoparticle (MSN) based drug delivery system (DDS) with dual-responsiveness was prepared for cancer therapy. To avoid the side reaction between the anti-cancer drug doxorubicin hydrochloride (DOX) and HA, host-guest interaction was applied to fabricate the DDS named DOX@MSN-SS-N=C-HA. The “nanocontainer” MSN was modified with benzene ring via both pH-sensitive benzoic imine bond and redox-sensitive disulfide linkage. When DOX was loaded in the pores of MSN, the channels were then capped by the “gatekeeper” β-CD grafted HA (HA-g-CD) through host-guest interaction between β-CD and benzene. HA endowed the drug carriers with the targeting capability in CD44 over-expressed cancer cells. After cellular uptake, the carriers could rapidly release DOX for cell apoptosis due to both the hydrolysis of benzoic imine bond at low pH and the cleavage of disulfide bond at a high concentration of glutathione (GSH) intracellular. In vitro drug release studies and in vitro cytotoxicity studies were taken to investigate the dual-responsiveness of the carriers. And the CD44-receptor mediated cancer cell targeting capability was investigated as well. In conclusion, the targeted dual-responsive complex DDS fabricated through host-guest interaction has promising potential in cancer therapy.

Introduction

Chemotherapy remains one of the major therapeutic approaches applied to treat cancer in clinic. However, the disadvantages of traditional chemotherapeutic drugs such as unfavorable pharmacokinetics, poor biodistribution and lack of selectivity for target tissues reduce the utilization of the drugs and cause serious side effects [1]. To tackle these problems, anti-cancer drug delivery systems (DDSs) based on nanotechnology have been introduced and developed rapidly in recent decades [1–4]. DDSs such as liposomal daunorubicin (DaunoXome), pegylated liposomal doxorubicin (Doxil), albumin nanoparticle based Nan-paclitaxel (Abraxane) and polymeric micelle paclitaxel (GenexolPM) have already been approved for clinical treatment of cancer [3,4]. These nanosized DDSs can be accumulated in tumor tissues more easily via enhanced permeability and retention (EPR) effect to improve the pharmacokinetics and biodistribution of the drugs, as well as to reduce their side effects [5]. Though the commercial DDSs represented by the liposomal doxorubicin can overcome part of the shortcomings of traditional anticancer drugs, they cannot or only modestly improve patients’ overall survival [3,6–9]. Therefore, more efforts are needed to develop novel advanced DDSs. The properties including controlled drug release based on stimuli- sensitivity [10,11] and ligand-mediated active cancer targeting [12–15] introduced make the newly reported DDSs with better therapeutic effects [1–4]. During the past decade, mesoporous silica nanoparticle (MSN) based DDSs have attracted considerable attention from scientists worldwide [16,17]. MSNs can be simply synthesized with tunable size, shape, pore size and volume [17,18], and are easy surface functionalization [16]. These advantages, as well as the high drug loading capacity and good biocompatibility, ensure that MSNs are excellent choices for designing safe and efficient drug carriers [16–18].

1- Introduction

2- Material and methods

3- Results and discussion

4- Conclusions

References

Abstract

Mesoporous silica nanoparticles with folic acid (MSN−COOH-Tet-HBP-FA) are able to mediate targeting and have a pH stimulation response character, and therefore have been successfully synthesized as vectors for antitumor drug delivery. The model drug is tetrandrine (Tet). The chemical structure and properties of these NPs were characterized through systematic characterization analyses. Their drug loading capacity was significantly improved through carboxy modification (26.86 % in max), and they exhibited pH-dependent drug release profiles(“zero pre-release” within 20 h in a normal physiological environment). In vitro cytotoxicity and cell uptake of the as-synthesized NPs in Hela and A549 cells were also evaluated, and exhibited high cytotoxicity and cell-targeted uptake capacity. It was concluded that MSN−COOH-Tet-HBP-FA could be used as a promising drug delivery system for cancer therapy.

Introduction

Cancer is currently considered to be a leading factor that threatens human lives, and chemotherapy remains one of the most common methods used for cancer treatment. However, traditional drugs are nonspecific and cannot discriminate cancer cells and normal cells, which not only limits the accumulation of drugs in tumor cells, but also leads to systemic toxicity and adverse side effects. In order to improve the efficacy of chemotherapy, many studies have been devoted to the development of tumor-targeted nanocarriers, which can be used to control the delivery of antitumor drugs. Using the enhanced permeation and retention (EPR) effects, researchers have developed multiple nanocarrier platforms, including liposomes, polymer nanoparticles, nano-micelles, and dendrimers, which are used to delivery anticancer drugs into tumor tissues. However, the EPR effect is not efficient enough to eradicate the side effects of cytotoxic drugs and to exert the anticancer therapy selectively in cancer cells. In order to enhance the targeting and tumoral uptake ability, the external surface of nanocarrier is often modified with various ligands, which can significantly enhance the interaction between the cancer cells and the nanocarriers[. Targeted agents typically include antibodies (such as monoclonal antibodies), peptides (such as Arg-Gly-Asp (RGD)), and small molecule compounds (such as folic acid).

1- Introduction

2- Multi-layer NPs for CRISPR-Cas9 delivery

3- Novel building blocks for multi-layer NPs

4- Conclusions and perspective

References

Abstract

The clustered regularly interspaced short palindromic repeat (CRISPR) has great potential to revolutionize biomedical research and disease therapy. The specific and efficient genome editing strongly depends on high efficiency of delivery of the CRISPR payloads. However, optimization of CRISPR delivery vehicles still remains a major obstacle. Recently, various non-viral vectors have been utilized to deliver CRISPR tools. Many of these vectors have multi-layer structures assembled. In this review, we will introduce the development of CRISPR-Cas9 systems and their general therapeutic applications by summarizing current CRISPR-Cas9 based clinical trials. We will highlight the multi-layer nanoparticles (NPs) that have been developed to deliver CRISPR cargos in vitro and in vivo for various purposes, as well the potential building blocks of multi-layer NPs. We will also discuss the challenges in making the CRISPR tools into viable pharmaceutical products and provide potential solutions on efficiency and biosafety issues.

Introduction

In recent years, a series of programmable DNA nuclease-dependent genome editing techniques have been developed to enable efficient genetic manipulation in eukaryotes, particularly in mammalian cells [1-3]. These genome-editing techniques used for gene knock-out or knock-in predominately include meganucleases, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the CRISPR-Cas system [4-7]. These technologies all employ endonucleases to induce double strand breaks (DSB) at intended sites in the genome, followed by DSB repair through different mechanisms including non-homologous end joining (NHEJ), homologous recombination (HR), homology-mediated end joining (HMEJ) and microhomology-mediated end joining (MMEJ) [8]. Among these genome editing techniques, CRISPR-Cas9 is a gene editing system derived from the bacterial adaptive immune system, which is capable of combating the invasive viral genome under the guidance of short sequence RNA. CRISPR-Cas9 system is highly versatile because of its simplicity and high efficiency, moreover, any genome sequence theoretically can be edited by this system. In principle, the whole genome can be site-specifically modified at the genetic level in cells and tissues with CRISPR-Cas9 system, which further allows researchers to study the relationship between gene mutations and biological phenotypes. CRISPR-Cas9 system has driven innovative applications from basic biology research to biotechnology and medicine [9].