In vitro and in vivo tests for therapeutic agents are typically conducted in sterile environments, but many target areas for drug delivery are home to thousands of microbial species. Here, we examine the behaviour of lipidic nanomaterials after exposure to representative strains of four bacterial species found in the gastrointestinal tract and skin. Small angle X-ray scattering measurements show that the nanostructure of monoolein cubic and inverse hexagonal phases are transformed, respectively, into inverse hexagonal and inverse micellar cubic phases upon exposure to a strain of live Staphylococcus aureus often present on skin and mucosa. Further investigation demonstrates that enzymatic hydrolysis and cell membrane lipid transfer are both likely responsible for this effect. The structural responses to S. aureus are rapid and significantly reduce the rate of drug release from monoolein-based nanomaterials. These findings are the first to demonstrate how a key species in the live human microbiome can trigger changes in the structure and drug release properties of lipidic nanomaterials. The effect appears to be strain specific, varies from patient to patient and body region to body region, and is anticipated to affect the bioapplication of monoglyceride-based formulations.

Helicobacter pylori infection is involved in gastric diseases such as peptic ulcer and adenocarcinoma. Approved antibiotherapies still fail in 10 to 40% of the infected patients and, in this scenario, targeted nanotherapeutics emerged as powerful allies for H. pylori eradication. Nano/microparticles conjugated with H. pylori binding molecules were developed to eliminate H. pylori by either (i) blocking essential mechanisms of infection, such as adhesion to gastric mucosa or (ii) binding and killing H. pylori through the release of drugs within the bacteria or at the site of infection. Glycan antigens (as Lewis B and sialyl-Lewis X), pectins, lectins, phosphatidylethanolamine and epithelial cell membranes were conjugated with nano/microparticles to successfully block H. pylori adhesion. Urea-coated nanoparticles were used to improve drug delivery inside bacteria through H. pylori UreI channel. Moreover, nanoparticles coated with antibodies against H. pylori and loaded with sono/photosensitizers, were promising for their application as targeted sono/photodynamic therapies. Further, non-specific H. pylori nano/microparticles, but only active in the acidic gastric environment, coated with binders to bacterial membrane, extracellular polymeric substances or to high temperature requirement A protease, were evaluated. In this review, an overview of the existing nanotherapeutics targeting H. pylori will be given and their rational, potential to counteract infection, as well as level of development will be presented and discussed.

Neurological disorders pose a huge worldwide challenge to the healthcare system, necessitating innovative strategies for targeted drug delivery to the central nervous system. Alzheimer\'s disease (AD) is an untreatable neurodegenerative condition characterized by dementia and alterations in a patient\'s physiological and mental states. Since ancient times, medicinal plants have been an important source of bioactive phytochemicals with immense therapeutic potential. This review investigates new and safer alternatives for prevention and treatment of disease related to inevitable side effects associated with synthetic compounds. This review examines how nanotechnology can help in enhancing the delivery of neuroprotective phytochemicals in AD. Nevertheless, despite their remarkable neuroprotective properties, these natural products often have poor therapeutic efficacy due to low bioavailability, limited solubility and imperfect blood brain barrier (BBB) penetration. Nanotechnology produces personalized drug delivery systems which are necessary for solving such problems. In overcoming these challenges, nanotechnology might be employed as a way forward whereby customized medication delivery systems would be established as a result. The use of nanocarriers in the design and application of important phytochemicals is highlighted by this review, which indicate potential for revolutionizing neuroprotective drug delivery. We also explore the complications and possibilities of using nanocarriers to supply nutraceuticals and improve patients\' standard of living, and preclinical as well as clinical investigations displaying that these techniques are effective in mitigating neurodegenerative diseases. In order to fight brain diseases and improve patient\'s health, scientists and doctors can employ nanotechnology with its possible therapeutic interventions.

Many strategies for regenerating the damaged tissues or degenerating cells are employed in regenerative medicine. Stem cell technology is a modern strategy of the recent approaches, particularly the use of mesenchymal stem cells (MCSs). The ability of MSCs to differentiate as well as their characteristic behaviour as paracrine effector has established them as key elements in tissue repair (Shaer et al., 20141). Recently, extracellular vesicles (EVs) shed by MSCs have emerged as a promising cell free therapy (Citation}Rani, S., Ryan, A. E., Griffin, M. D., and Ritter, T., 20152). This comprehensive review encompasses MSCs-derived exosomes and their therapeutic potential as nanotherapeutics. We also discuss their potency as drug delivery nano-carriers in comparison with liposomes. A better knowledge of EVs behaviour in vivo and of their mechanism of action are key to determine parameters of an optimal formulation in pilot studies and to establish industrial processes.

In recent years, enzyme therapy strategies have rapidly evolved to catalyze essential biochemical reactions with therapeutic potential. These approaches hold particular promise in addressing rare genetic disorders, cancer treatment, neurodegenerative conditions, wound healing, inflammation management, and infectious disease control, among others. There are several primary reasons for the utilization of enzymes as therapeutics: their substrate specificity, their biological compatibility, and their ability to generate a high number of product molecules per enzyme unit. These features have encouraged their application in enzyme replacement therapy where the enzyme serves as the therapeutic agent to rectify abnormal metabolic and physiological processes, enzyme prodrug therapy where the enzyme initiates a clinical effect by activating prodrugs, and enzyme dynamic or starving therapy where the enzyme acts upon host substrate molecules. Currently, there are >20 commercialized products based on therapeutic enzymes, but approval rates are considerably lower than other biologicals. This has stimulated nanobiotechnology in the last years to develop nanoparticle-based solutions that integrate therapeutic enzymes. This approach aims to enhance stability, prevent rapid clearance, reduce immunogenicity, and even enable spatio-temporal activation of the therapeutic catalyst. This comprehensive review delves into emerging trends in the application of therapeutic enzymes, with a particular emphasis on the synergistic opportunities presented by incorporating enzymes into nanomaterials. Such integration holds the promise of enhancing existing therapies or even paving the way for innovative nanotherapeutic approaches.

The availability of non-invasive drug delivery systems capable of efficiently transporting bioactive molecules across the blood-brain barrier to specific cells at the injury site in the brain is currently limited. Delivering drugs to neurons presents an even more formidable challenge due to their lower numbers and less phagocytic nature compared to other brain cells. Additionally, the diverse types of neurons, each performing specific functions, necessitate precise targeting of those implicated in the disease. Moreover, the complex synthetic design of drug delivery systems often hinders their clinical translation. The production of nanomaterials at an industrial scale with high reproducibility and purity is particularly challenging. However, overcoming this challenge is possible by designing nanomaterials through a straightforward, facile, and easily reproducible synthetic process. Methods: In this study, we have developed a third-generation 2-deoxy-glucose functionalized mixed layer dendrimer (2DG-D) utilizing biocompatible and cost-effective materials via a highly facile convergent approach, employing copper-catalyzed click chemistry. We further evaluated the systemic neuronal targeting and biodistribution of 2DG-D, and brain delivery of a neuroprotective agent pioglitazone (Pio) in a pediatric traumatic brain injury (TBI) model. Results: The 2DG-D exhibits favorable characteristics including high water solubility, biocompatibility, biological stability, nanoscale size, and a substantial number of end groups suitable for drug conjugation. Upon systemic administration in a pediatric mouse model of traumatic brain injury (TBI), the 2DG-D localizes in neurons at the injured brain site, clears rapidly from off-target locations, effectively delivers Pio, ameliorates neuroinflammation, and improves behavioral outcomes. Conclusions: The promising in vivo results coupled with a convenient synthetic approach for the construction of 2DG-D makes it a potential nanoplatform for addressing brain diseases.

A new type of 0-dimensional carbon-based materials called graphene quantum dots (GQDs) is gaining significant attention as a non-toxic and eco-friendly nanomaterial. GQDs are nanomaterials composed of sp2hybridized carbon domains and functional groups, with their lateral size less than 10 nm. The unique and exceptional physical, chemical, and optical properties arising from the combination of graphene structure and quantum confinement effect due to their nano-size make GQDs more intriguing than other nanomaterials. Particularly, the low toxicity and high solubility derived from the carbon core and abundant edge functional groups offer significant advantages for the application of GQDs in the biomedical field. In this review, we summarize various synthetic methods for preparing GQDs and important factors influencing the physical, chemical, optical, and biological properties of GQDs. Furthermore, the recent application of GQDs in the biomedical field, including biosensor, bioimaging, drug delivery, and therapeutics are discussed. Through this, we provide a brief insight on the tremendous potential of GQDs in biomedical applications and the challenges that need to be overcome in the future.

Anticancer drugs are often associated with limitations such as poor stability in aqueous solutions, limited cell membrane permeability, nonspecific targeting, and irregular drug release when taken orally. One possible solution to these problems is the use of nanocarriers of drug molecules, particularly those with targeting ability, stimuli-responsive properties, and high drug loading capacity. These nanocarriers can improve drug stability, increase cellular uptake, allow specific targeting of cancer cells, and provide controlled drug release. While improving the therapeutic efficacy of cancer drugs, contemporary researchers also aim to reduce their associated side effects, such that cancer patients are offered with a more effective and targeted treatment strategy. Herein, a set of nine porous covalent organic frameworks (COFs) were tested as drug delivery nanocarriers. Among these, paclitaxel loaded in COF-3 was most effective against the proliferation of ovarian cancer cells. This study highlights the emerging potential of COFs in the field of therapeutic drug delivery. Due to their biocompatibility, these porous COFs provide a viable substrate for controlled drug release, making them attractive candidates for improving drug delivery systems. This work also demonstrates the potential of COFs as efficient drug delivery agents, thereby opening up new opportunities in the field of sarcoma therapy.

Botanical preparations for herbal medicine have received more and more attention from drug researchers, and the extraction of active ingredients and their successful clinical application have become an important direction of drug research in major pharmaceutical companies, but the complexity of extracts, multiple side effects, and significant individual differences have brought many difficulties to the clinical application of herbal preparations. It is noteworthy that extracellular vesicles as active biomolecules extracted from medicinal plants are believed to be useful for the treatment of a variety of diseases, including cancer, inflammation, regenerative-restorative and degenerative diseases, which may provide a new direction for the clinical utilization of herbal preparations. In this review, we sort out recent advances in medicinal plant extracellular vesicles and discuss their potential as disease therapeutics. Finally, future challenges and research directions for the clinical translation of medicinal plant extracellular vesicles are also discussed, and we expect that continued development based on medicinal plant extracellular vesicles will facilitate the clinical application of herbal preparations.

A wide variety of natural bioactive compounds derived from plants have demonstrated significant clinical relevance in the treatment of various diseases such as cancer, chronic disease, and inflammation. An increasing number of studies have surfaced that give credence to the potential of plant-derived vesicle-like nanoparticles (PDVLNs) as compelling candidates for a drug delivery system (DDS). PDVLNs are cost-effective production, non-toxicity and non-immunogenicity and fascinating bi-ocompatibility. In this review, we attempt to comprehensively review and consolidate the position of PDVLNs as next-generation drug delivery nanoplatforms. We aim to give a quick glance to readers of the current developments of PDVLNs, including their biogenesis, characteristic features, composition, administration routes, advantages, and application. Further, we discuss the advantages and limitations of PDVLNs. We expect that the role of PDVLNs in drug delivery will be significantly enhanced, thus positioning them as the next generation of therapeutic modalities in the foreseeable future.