Nanomaterials, especially nanofibers, hold considerable promise as drug delivery systems (DDS) by providing targeted administration of drugs due to their unique properties, such as large surface area, high porosity, and mechanical robustness. Nanofibers can be fabricated using various techniques like electrospinning, self-assembly, phase separation, and template synthesis, offering properties such as adjustable size, shape, high precision, and biodegradability. Additionally, features such as multiple target functionalization, controlled release of the drug, and prolonged circulation of the drug make nanofibers particularly suitable for biomedical applications, including drug delivery, tissue regeneration, and biosensing. This comprehensive review explores the characteristics, types, fabrication methods, and applications of nanofibers. Diverse types of polymer nanofibers are used in drug delivery, such as blended nanofibers, core-shell nanofibers, and layer-by-layer assembly, each demonstrating their own advantages in controlled drug release and targeted therapy. Electrospun nanofibers are extensively utilized in biomedical applications due to their superior mechanical performance and high porosity and advancements in coaxial electrospinning enabling the fabrication of core-shell nanofibers, offering controlled drug release kinetics and protection of loaded molecules. These nanofibers demonstrate enhanced bioactivity and biocompatibility and can find application in tissue engineering. Furthermore, this review addresses the challenges associated with nanofiber production, including reproducibility and scalability. Nanofibers exhibit the potential to revolutionize medical treatment across diverse therapeutic areas. Future research directions and challenges in nanofiber-based drug delivery discussed in this review offer guidance for further advancements in this rapidly evolving field.

Biomacromolecules are viewed as promising drugs due to their specific functions in biological processes, biocompatibility, and pharmacological efficacy. Injective administration, chosen to avoid intestinal barriers, may in turn lead to immediate decay in the circulation system, unreliable targeting performance, or the induction of immune responses. For some biomacromolecules, chemically modified proteins have been developed for practical use. Various cargo or carrier systems are under development but have been delayed by technical difficulties. We present self-assembled nanocapsules with diameters ranging from 100 to 500 nm that can be deployed in physiological buffers to enclose various substances present in the buffers at the same time. Our amphiphilic nanocapsule, consisting of silole-core dendrimer products as the hydrophobic part and green fluorescent protein (GFP) derivatives as the hydrophilic part, connects and assembles spontaneously when mixed in solutions while engulfing dissolved or dispersed compounds together in a dose-dependent manner and shows unique optical characteristics because the dendrimer products exhibit aggregation-induced emission. Furthermore, the emission of the dendrimer causes considerable fluorescence resonance energy transfer (FRET) to GFP derivatives upon association. We could easily monitor assemblies by FRET states and particle sizes and have confirmed a stable presence in the buffer for at least a month. Further tracking of nanocapsules by fluorescence confirmed efficient uptake into some cancer cells. Nanocapsules based on GFP variants with or without a cell-surface-specific tag demonstrated that the tag improved the potential for specific targeted delivery. There were also indications that the nanocapsules became unstable after cellular uptake in the intracellular environment. We report here the simple preparation of traceable, stable, and biocompatible self-assembled nanocapsules as the basis for a versatile drug delivery system.

Recently, the incidence of brain diseases, such as central nervous system degenerative diseases, brain tumors, and cerebrovascular diseases, has increased. However, the blood-brain barrier (BBB) limits the effective delivery of drugs to brain disease areas. Therefore, the mainstream direction of new drug development for these diseases is to engineer drugs that can better cross the BBB to exert their effects in the brain. This paper reviews the research progress and application of the main trans-BBB drug delivery strategies (receptor/transporter-mediated BBB crossing, focused ultrasound to open the BBB, adenosine agonist reversible opening of the BBB, aromatic resuscitation, transnasal administration, cell-mediated trans-BBB crossing, and viral vector system-mediated brain drug delivery). Meanwhile, the potential applications, advantages, and disadvantages of these strategies for crossing the BBB are analyzed. Finally, the future development prospects of strategies for crossing the BBB are also discussed. These strategies have potential value for treating brain diseases.

Immune-related drug delivery systems (DDSs) in humanized mouse models are at the forefront of cancer research and serve as bridges between preclinical studies and clinical applications. These systems offer unique platforms for exploring new therapies and understanding their interactions with human cells and the immune system. Here, we focus on a DDS and a peripheral blood mononuclear cell (PBMC)-engrafted humanized mouse model that we recently developed, and consider some of the key components, challenges, and applications to advance these systems towards better cancer treatment on the basis of a better understanding of the immune response. Our DDS is unique and has a dual function, an anticancer effect and a capacity to fine-tune the immune reaction. The PBL-NOG-hIL-4-Tg mouse system is superior to other available humanized mouse systems for the development of such multifunctional DDSs because it supports the rapid reconstruction of an individual donor\'s immunity and avoids the onset of graft-versus-host disease.

Immunotherapy combats tumors by enhancing the body\'s immune surveillance and clearance of tumor cells. Various nucleic acid drugs can be used in immunotherapy, such as DNA expressing cytokines, mRNA tumor vaccines, small interfering RNAs (siRNA) knocking down immunosuppressive molecules, and oligonucleotides that can be used as immune adjuvants. Nucleic acid drugs, which are prone to nuclease degradation in the circulation and find it difficult to enter the target cells, typically necessitate developing appropriate vectors for effective in vivo delivery. Biomimetic drug delivery systems, derived from viruses, bacteria, and cells, can protect the cargos from degradation and clearance, and deliver them to the target cells to ensure safety. Moreover, they can activate the immune system through their endogenous activities and active components, thereby improving the efficacy of antitumor immunotherapeutic nucleic acid drugs. In this review, biomimetic nucleic acid delivery systems for relieving a tumor immunosuppressive microenvironment are introduced. Their immune activation mechanisms, including upregulating the proinflammatory cytokines, serving as tumor vaccines, inhibiting immune checkpoints, and modulating intratumoral immune cells, are elaborated. The advantages and disadvantages, as well as possible directions for their clinical translation, are summarized at last.

Dry eye syndrome (DES) is a dynamic, chronic disease of the ocular surface and ocular appendages caused by inflammation. The most common symptoms include redness, itching, and blurred vision, resulting from dysfunction of the meibomian glands and impaired tear-film production. Factors contributing to the development of DES include environmental elements, such as UV radiation, and internal elements, such as hormonal imbalances. These factors increase oxidative stress, which exacerbates inflammation on the surface of the eye and accelerates the development of DES. In recent years, the incidence of DES has risen, leading to a greater need to develop effective treatments. Current treatments for dry eye are limited and primarily focus on alleviating individual symptoms, such as reducing inflammation of the ocular surface. However, it is crucial to understand the pathomechanism of the disease and tailor treatment to address the underlying causes to achieve the best possible therapeutic outcomes. Therefore, in this review, we analyzed the impact of oxidative stress on the development of DES to gain a better understanding of its pathomechanism and examined recently developed nanosystems that allow drugs to be delivered directly to the disease site.

We aimed to investigate the chemical and physical properties of nano silver fluoride sustained release orthodontic elastomerics (NSF-RE) and determine their antimicrobial and antibiofilm formation activities against Streptococcus mutans. Orthodontic elastomerics were dip-coated with NSF solution in ethyl cellulose (EC) and polyethylene glycol 6000 (PEG). The studied groups included NSF (no EC/PEG), NSF-E (EC), NSF-EP1 (EC:PEG, 4:1), and NSF-EP2 (EC:PEG, 2:1). The cumulative release of silver nanoparticles (AgNPs) and fluoride, along with the compatibility of the tensile force with orthodontic brackets, was evaluated. The antimicrobial activity was evaluated using an agar diffusion test. The inhibition of biofilm formation was evaluated using colony-forming units (CFUs), biofilm thickness, and the live/dead cell ratio. NSF-RE containing EC sustained the release of AgNPs and fluoride for > 7 days. Tensile forces were not significantly different among the groups. The inhibition zone was 2.64- and 1.31-fold larger with NSF-EP2 than that with NSF and NSF-E, respectively. NSF-EP2 was the most effective in inhibiting biofilm formation with significant reductions in CFUs, biofilm thickness, and live/dead cell ratio by 57, 86, and 96%, respectively, as compared to those in the control group. Overall, sustained release of AgNPs and fluoride by NSF-RE provides antimicrobial and antibiofilm effects against S. mutans.

In this study, the potential of borophene (BOR) as a drug delivery system for resveratrol (RVT) was explored to evaluate its efficacy in cancer treatment. The excited, electronic, and geometric states of RVT, BOR, and the borophene-adsorbed resveratrol complex (BOR@RVT) were calculated to assess BOR\'s suitability as a drug carrier. Noncovalent interaction (NCI) plots indicated a weak force of attraction between BOR and RVT, which facilitates the offloading of RVT at the target site. Frontier molecular orbital (FMO) analysis showed that during electron excitation from Highest Occupied Molecular Orbital (HOMO) to Lowest Unoccupied Molecular Orbital (LUMO), charge transfer occurs from RVT to BOR. This was further confirmed by charge decomposition analysis (CDA). Calculations for the excited state of BOR@RVT revealed a red shift in the maximum absorption wavelength (λmax), indicating a photoinduced electron transfer (PET) process across various excited states. PET analysis demonstrated fluorescence quenching due to this interaction. Our findings suggest that BOR holds significant potential as a drug delivery vehicle for cancer treatment, offering a promising platform for the development of advanced drug delivery systems.

The modified cell-penetrating peptide Pas2r12 can deliver antibodies (IgG, 150 kDa) and enhanced green fluorescent protein (EGFP1, 27 kDa) into the cytosol through caveolae-dependent endocytosis. In this study, we determined the effect of Caveolin-1 overexpression on the cytosolic delivery of EGFP by Pas2r12. Three types of Caveolin-1 overexpressing strains were isolated, including Cav1L (low), Cav1M (medium), and Cav1H (high), using HEK293 as the parent cell line. We found that the number of caveolae on the surface of the Caveolin-1-overexpressing strains was similar to that of HEK293. We examined the cytosolic delivery rate of EGFP by Pas2r12. In the Cav1L and Cav1M cells, there was little change compared with HEK293; however, in Cav1H, the rate was significantly decreased. Moreover, the amount of EGFP uptake into the cells (total intracellular EGFP) showed an increasing trend in Cav1H compared with HEK293. These results indicate that in Cav1H, the amount of EGFP uptake into the cells increases, whereas the cytosolic delivery rate of EGFP decreases. This suggests that high overexpression of Caveolin-1 inhibits the transition of EGFP from endosomes to the cytosol.

Exosomes are extracellular nanovesicles secreted by all cell types and have been studied to understand and treat many human diseases. Exosomes are involved in numerous physiological and pathological processes, intercellular communication, and the transfer of substances. Over the years, several studies have explored mammalian-derived exosomes for therapeutic and diagnostic uses. Only recently have plant-derived extracellular vesicles (EVs) attracted attention for their ability to overcome many defects associated with using mammalian-derived extracellular vesicles, such as safety and scale-up issues. The ease of large-scale production, low toxicity, low immunogenicity, efficient cellular uptake, high biocompatibility, and high stability of these nanovesicles make them attractive for drug delivery systems. In addition, their native contents of proteins, miRNAs and secondary metabolites could be exploited for pharmaceutical applications in combination with other drugs. The present review intends to provide adequate tools for studying and developing drug delivery systems based on plant-derived EVs. Therefore, indications concerning extraction methods, characterisation, and drug loading will be offered. Their biological composition and content will also be reported. Finally, the current applications of these systems as nanocarriers for pharmacologically active substances will be shown.