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Simple Summary: Glioblastoma (GBM), a serious brain cancer, has poor treatment outcomes despite surgery, radiation, and chemotherapy. The blood–brain barrier (BBB) makes GBM-targeted drug delivery difficult. Recent studies have shown that nanomedicine delivery systems (NDDSs) can target GBM safely and effectively. In this review, we look at ways to overcome the BBB with NDDSs in preclinical studies, summarize the clinical progress, and discuss strategies to improve NDDSs and speed up their use in GBM treatment through clinical trials. Glioblastoma (GBM) is a prevalent type of malignancy within the central nervous system (CNS) that is associated with a poor prognosis. The standard treatment for GBM includes the surgical resection of the tumor, followed by radiotherapy and chemotherapy; yet, despite these interventions, overall treatment outcomes remain suboptimal. The blood–brain barrier (BBB), which plays a crucial role in maintaining the stability of brain tissue under normal physiological conditions of the CNS, also poses a significant obstacle to the effective delivery of therapeutic agents to GBMs. Recent preclinical studies have demonstrated that nanomedicine delivery systems (NDDSs) offer promising results, demonstrating both effective GBM targeting and safety, thereby presenting a potential solution for targeted drug delivery. In this review, we first explore the various strategies employed in preclinical studies to overcome the BBB for drug delivery. Subsequently, the results of the clinical translation of NDDSs are summarized, highlighting the progress made. Finally, we discuss potential strategies for advancing the development of NDDSs and accelerating their translational research through well-designed clinical trials in GBM therapy. [ABSTRACT FROM AUTHOR]

AbstractNanotechnology has significantly impacted drug discovery and development over the past three decades, offering novel insights and expanded treatment options. Key to this field is nanoparticles, ranging from 1 to 100 nanometres, with unique properties distinct from larger materials. Selenium nanoparticles (SeNPs) are particularly promising due to their low toxicity and selective cytotoxicity against cancer cells. They have shown efficacy in reducing various cancers types and mitigating conditions like diabetic nephropathy and neurological disorders, such as Alzheimer’s disease. This review highlights SeNPs’ role in enhancing drug delivery systems, improving the absorption of water-soluble compounds, proteins, peptides, vaccines, and other biological therapies. By modifying nanoparticle surfaces with targeting ligands, drug delivery can achieve precise site-specific delivery, increasing effectiveness. SeNPs can be synthesised through physical, chemical, and biological methods, each offering advantages in stability, size, and application potential. Additionally, SeNPs enhance immune responses and reduce oxidative stress, validating their role in biotherapy and nanomedicine. Their ability to target macrophages and regulate polarisation underscores their potential in antimicrobial therapies. Recent advancements, such as mannosylated SeNPs for targeted delivery, exemplify innovative nanotechnology applications in medicine. Overall, SeNPs represent a promising frontier in nanomedicine, offering new avenues for treating and managing various diseases. [ABSTRACT FROM AUTHOR]

Paclitaxel is one of the most widely utilized anticancer drug. It displays a range of antitumor action, particularly against ovarian cancer, urologic malignancies, head tumor, and Kaposi's sarcoma. However, due to its highly lipophilic nature, poor fluid dissolvability of less 0.01 mg/mL and lack of ionizing functionalities which may enhance its solubility, there are substantial challenges associated with Paclitaxel delivery. Paclitaxel exhibited promising effects when formulated in combination with ethanol and Cremophor EL, as Taxol®. However, it is associated with various side effects, including hypersensitivity, hypotension, and peripheral neuropathy. The albumin-based Paclitaxel, Abraxane®, is a superior alternative to Taxol® as it diminishes the side effects related to Cremophor EL. Abraxane® is regarded as the gold standard for cancer treatment, but its 21% response rate suggests that more research is needed. Furthermore, the large-scale clinical use of this drug has faced considerable delay because of the absence of suitable delivery vehicles. Therefore, necessitates is the development of an alternate form of Paclitaxel that has both superior aqueous solubility as well as fewer side-effects. During the last decade, various methodologies have been explored to improve Paclitaxel's solubility with the help of co-solvents and inclusion complexes. Additionally, various methodologies report of passive targeting of cancer cells using nanoparticles, nanosuspensions, Rotaxane (a mechanically interlocked molecular system), liposomes, micelles, emulsions, gels, pastes, etc. Herein, we have comprised a brief report on various delivery techniques for Paclitaxel with improved therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Since early developments in the field of mesoporous materials, mesoporous silica has attracted large interest in drug delivery, as they display an ordered array of pores with diameters ranging from 2 to 50 nm, which can be loaded with drugs. Mesoporous silica dissolves at physiological pH, triggering the release of loaded drugs. Several studies have focused on determining the key factors that determine the biodistribution, biocompatibility, and toxicity both in vitro or in vivo. However, in vivo studies focused on the degradation of mesoporous silica materials are very scarce, despite its relevance for drug release. In this perspective, recent works addressing mesoporous materials degradation in the context of drug delivery are discussed, first from a physicochemical point of view, and secondly in in vivo settings, in animal models that are the closest conditions to the encountered when the mesoporous materials are administered to humans. Finally, further discussion about the future directions in the design of mesoporous nanomaterials for therapy and for the study of their biological fate are presented. [ABSTRACT FROM AUTHOR]

Biomimetic and biohybrid micro/nano‐structures involve the replication and creation of technologies, structures, and materials based on biological systems at the micrometer and nanometer scale. These strategies harness the natural biological principles to develop innovative treatment methods and advanced microstructure devices for noninvasive therapies. In this study, a detailed overview of fabrication processes, magnetically assisted locomotive techniques, and potential applications of biomimetic and biohybrid micro/nano‐machines are presented. The latest advancements in magnetically actuated biomimetic structures, such as annelid‐worm‐like microswimmers, jellyfish‐shaped microparticles, fish‐shaped microswimmers, and walnut‐shaped micromotors are explored. Additionally, the magnetic biohybrid systems, including sunflower seed‐based micro‐perforators, nanomotors extracted from the bamboo stem, sperm cell‐based micromotors, bacteria‐based robots, scaffold‐based microrobots, DNA‐based micromotors, microalgae‐based microswimmers, and red blood cell‐based microswimmers are also examined. A thorough investigation of the magnetically assisted locomotive behavior of these microstructure devices in biological Newtonian fluids, featuring cork‐screw motion, undulatory motion, surface wrinkling motion, traveling wave‐like motion, and ciliary stroke motion is discussed. Furthermore, unprecedented and innovative treatment methods developed using these minuscule devices such as cervical cancer treatment using tetrapod hybrid sperm micromotors, tissue regeneration using silk fibroin protein‐based magnetic microscale scaffolds, and doxorubicin drug delivery using mushroom‐based microrobots is extensively presented. [ABSTRACT FROM AUTHOR]

Magnetic nanomaterials have emerged as an effective drug‐delivery platform for targeted imaging and therapy. However, it remains challenging to fabricate biodegradable magnetic nanoparticles with controllable drug release behaviors and strong magnetic responsiveness. Here an asiaticoside‐loaded biodegradable magnetic vesicle is developed based on the self‐assembly of amphiphilic block copolymer tethered superparamagnetic iron oxide nanoparticles. Thanks to the collective properties, the magnetic vesicles show stronger magnetic responsiveness than individual nanoparticles. Additionally, the magnetic vesicles are dissociated within weeks owing to the biodegradable polymer backbone, which can significantly improve the long‐term biocompatibility of the nanomaterials. The asiaticoside‐loaded magnetic vesicles can readily release the payloads in an alternating magnetic field, likely due to the rising local temperature over the phase transition temperature of the polymers attached on nanoparticles. This work provides new insights into the design and construction of biodegradable magnetic nanomedicines for targeted drug delivery. [ABSTRACT FROM AUTHOR]

Polyoxometalates (POMs) are multifunctional anionic metal‐oxygen complexes with structural and electronic diversity, as well as tunable acid‐base and redox properties, resulting in their potential as building blocks for constructing temperature‐responsive polyoxometalates‐based materials (TRPMs). TRPMs represent a class of intelligent materials exhibiting property changes in response to temperature fluctuations, offering distinctive applications in various fields such as catalysis, medicine, sensors, imaging, and so on. Though many TRPMs are reported, a systematic review including recent advances is still absent. This review provides insights into recent advancements in temperature‐responsive mechanisms, nanostructure design strategies, and the characterization of TRPMs. Special emphasis is placed on enhancing the temperature‐responsive properties of TRPMs by incorporating POMs into suitable organic ligands, such as ionic liquid cations, deep eutectic solvent cations, cationic surfactants, and polymers. The incorporation of organic ligands with POMs not only enables temperature‐responsive phase transitions but also enhances other properties, such as catalyst selectivity and drug loading capacity, expanding TRPMs applications. Consequently, this review summarizes the applications of TRPMs in catalysis, drug delivery and release, and chemical sensing, as well as discusses future technological challenges. The in‐depth understanding of TRPMs may help in the design of TRPMs from the nanoscale, guiding and inspiring future development. [ABSTRACT FROM AUTHOR]

The development of multifunctional organic materials represents a vibrant area of research, with applications spanning from biosensing to drug delivery. This study shows the development of a multifunctional bioelectronic device suitable for prolonged temperature monitoring and drug delivery applications. The device relies on a conducting and thermo‐responsive hydrogel made of poly(3,4‐ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) and poly(N‐isopropylacrylamide) (PNIPAM). This multifunctional hydrogel is 4D printable by Digital Light Processing (DLP) method and exhibits optimal biocompatibility. The hydrogel features a low critical solution temperature (LCST) ≈35 °C, above which its resistance changes dramatically due to the shrinkage it undergoes with temperature. The integration of PNIPAM/PEDOT hydrogel into an organic electrochemical transistor (OECT) as the gate electrode allows to generate a miniaturized bioelectronic device with a reversible response to temperature variations between 25 to 45 °C, along with high sensitivity of 0.05 °C−1. Furthermore, the PNIPAM/PEDOT hydrogel demonstrates its utility in drug delivery, achieving an Insulin‐FITC release rate of 82 ± 4% at 37 °C, mimicking human body conditions. The hydrogel's functionality to store and release the insulin does not compromise its thermo‐responsivity and the overall performance of the OECT. This multifunctional OECT opens new avenues for the development of customizable and personalized sensing and drug‐delivery systems. [ABSTRACT FROM AUTHOR]

Cancer is ranked among the top causes of mortality throughout the world. Conventional therapies are associated with toxicity and undesirable side effects, rendering them unsuitable for prolonged use. Additionally, there is a high occurrence of resistance to anticancer drugs and recurrence in certain circumstances. Hence, it is essential to discover potent anticancer drugs that exhibit specificity and minimal unwanted effects. Curcumin, a polyphenol derivative, is present in the turmeric plant (Curcuma longa L.) and has chemopreventive, anticancer, radio-, and chemo-sensitizing activities. Curcumin exerts its anti-tumor effects on cancer cells by modulating the disrupted cell cycle through p53-dependent, p53-independent, and cyclin-dependent mechanisms. This review provides a summary of the formulations of curcumin based on nanospheres, since there is increasing interest in its medicinal usage for treating malignancies and tumors. Nanospheres are composed of a dense polymeric matrix, and have a size ranging from 10 to 200 nm. Lactic acid polymers, glycolic acid polymers, or mixtures of them, together with poly (methyl methacrylate), are primarily used as matrices in nanospheres. Nanospheres are suitable for local, oral, and systemic delivery due to their minuscule particle size. The majority of nanospheres are created using polymers that are both biocompatible and biodegradable. Previous investigations have shown that the use of a nanosphere delivery method can enhance tumor targeting, therapeutic efficacy, and biocompatibility of different anticancer agents. Moreover, these nanospheres can be easily taken up by mammalian cells. This review discusses the many curcumin nanosphere formulations used in cancer treatment. [ABSTRACT FROM AUTHOR]

In the current study, we report the preparation of an injectable hydrogel by poly (N-isopropylacrylamide)-g-chitosan copolymer (CS-g-PNIPAAm)/gold nanoparticles (CS-g-PNIPAAm@AuNPs) hybrid hydrogel formation with gelatin using genipin as chemical crosslinker aimed for the local delivery of doxorubicin (DOX) in the breast cancer treatment. To prepare (CS-g-PNIPAAm), carboxyl terminated PNIPAAm was prepared via free radical polymerization in the presence of 3-mercaptopropionic acid and it was further grafted to CS via amine conjugation reaction. The chemical structure and porous architecture of the prepared hydrogel were characterized by FT-IR and SEM tests, respectively. The synthesized hydrogel was evaluated for in vitro degradation test. To assess the rheological behavior of hydrogels such as storage and loss modulus, the rheological test was performed. The DOX was released from the CS-g-PNIPAAm@AuNPs hydrogel in a pH-responsive manner which revealed an enriched release of DOX in acidic media. The cytotoxicity evaluation indicated that the prepared hydrogel alone remained cytocompatible on MCF-7 cells, while the DOX-loaded CS-g-PNIPAAm@AuNPs hydrogel could prompt cytotoxicity in examined cells. Based on these results, the DOX-loaded CS-g-PNIPAAm@AuNPs hydrogel could be considered an injectable thermo and pH-responsive system for the local delivery of DOX to breast cancer tumor cells. [ABSTRACT FROM AUTHOR]

To manufacture, feature and analyze the potential of materials to be used as raw material for drug delivery systems for the treatment of overactive bladder. Four distinct mixtures of oxybutynin and polymers ethylene vinyl acetate (EVA) and high-density polyethylene (PE) were prepared via compression molding and hot melt extrusion. The materials were characterized regarding their physicochemical and mechanical properties as well as drug release potential. Promising results were obtained in which the release of oxybutynin was observed for more than 250 days from both EVA and HDPE matrices. The obtained data demonstrate it is possible to manufacture HDPE- and EVA-based samples with the incorporation of oxybutynin, and the EVA samples presented an adequate release profile. The results are promising for the development of an intravesical device with drug delivery, especially because super dose risk is extinguished when considering the release from a monolithic release system. [ABSTRACT FROM AUTHOR]

Multimodal treatment of cancer is an unstoppable revolution in clinical application. However, designing a platform that integrates therapeutic modalities with different pharmacokinetic characteristics remains a great challenge. Herein, we designed a universal lipid nanoplatform equipping a ROS-cleavable docetaxel prodrug (DTX-L-DTX) and an NF-E2-related factor 2 (NRF2) inhibitor (clobetasol propionate, CP). This simply fabricated nanomedicine enables superior synergistic molecularly targeted/chemo/radio therapy for lung cancer cascade by a transcription factor-driven ROS self-sustainable motion. Chemotherapy is launched via ROS-triggered DTX release. Subsequently, CP inhibits the expression of NRF2 target genes, resulting in efficient targeted therapy, meanwhile inducing sustained ROS generation which in turn facilitates chemotherapy by overcoming ROS consumption during the DTX release process. Finally, the introduction of radiotherapy further amplifies ROS, offering continuous mutual feedback to amplify the ultimate treatment performance. This strategy is conceptually and operationally simple, providing solutions to challenges in clinical cancer treatment and beyond. A transcription factor-driven ROS self-sustainable strategy developed herein empowers the flawless blend of targeted therapy, chemotherapy, and radiotherapy, three first-line therapies for lung cancer. [Display omitted] • A lipid nanodrug loaded with a targeted inhibitor and a chemo-prodrug is developed. • This nanodrug enables a transcription factor-driven ROS self-sustainable motion. • This ROS self-sustainable motion in-turn improves chemo-prodrug activation. • This nanodrug facilitates synergistic multimodal lung cancer therapy. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) can be designed for targeted delivery in cancer nanomedicine, but the challenge is a low delivery efficiency (DE) to the tumor site. Understanding the impact of NPs' physicochemical properties on target tissue distribution and tumor DE can help improve the design of nanomedicines. Multiple machine learning and artificial intelligence models, including linear regression, support vector machine, random forest, gradient boosting, and deep neural networks (DNN), were trained and validated to predict tissue distribution and tumor delivery based on NPs' physicochemical properties and tumor therapeutic strategies with the dataset from Nano-Tumor Database. Compared to other machine learning models, the DNN model had superior predictions of DE to tumors and major tissues. The determination coefficients (R2) for the test datasets were 0.41, 0.42, 0.45, 0.79, 0.87, and 0.83 for DE in tumor, heart, liver, spleen, lung, and kidney, respectively. All the R2 and root mean squared error (RMSE) results of the test datasets were similar to the 5-fold cross validation results. Feature importance analysis showed that the core material of NPs played an important role in output predictions among all physicochemical properties. Furthermore, multiple NP formulations with greater DE to the tumor were determined by the DNN model. To facilitate model applications, the final model was converted to a web dashboard. This model could serve as a high-throughput pre-screening tool to support the design of new and efficient nanomedicines with greater tumor DE and serve as an alternative tool to reduce, refine, and partially replace animal experimentation in cancer nanomedicine research. [Display omitted] • Multiple quantitative structure-activity relationship (QSAR) models were developed. • The models can predict tumor delivery and tissue distribution of nanoparticles. • Several machine learning algorithms were applied to train and test the models. • Numerous nanoparticle formulations with high tumor delivery were proposed. • The best model was converted to a user-friendly web dashboard. [ABSTRACT FROM AUTHOR]

Recent advancements in cancer treatment have underscored the inadequacy of conventional monotherapies in addressing complex malignant tumors. Consequently, there is a growing interest in synergistic therapies capable of overcoming the limitations of monotherapies, leading to more personalized and effective approaches. Among these, the combination of photothermal therapy (PTT) and chemotherapy has emerged as a promising avenue for tumor management. In this study, we present a novel approach utilizing thermoresponsive mesoporous silica nanoparticles (MSN) as a delivery system for the chemotherapeutic drug doxorubicin. By incorporating photothermal agent copper sulfide (CuS) nanoparticles into the MSN, the resulting composite material exhibits potent photothermal properties. Furthermore, the integration of an upper critical solution temperature (UCST) polymer within the silica outer layer serves as a "gatekeeper", enabling precise control over drug release kinetics. This innovative nanomaterial effectively merges thermoresponsive behavior with PTT, thereby minimizing the collateral damage associated with traditional chemotherapy on healthy tissues. Moreover, in both in vitro studies using mouse breast carcinoma cells (4 T1) and in vivo experiments utilizing a 4 T1 tumor-bearing mouse model, our nanomaterials demonstrated synergistic effects, enhancing the anti-tumor efficacy of combined PTT and chemotherapy. With its remarkable photothermal conversion efficiency, robust stability, and biocompatibility, the UCST-responsive nanoplatform holds immense potential for clinical applications. Upon exposure to NIR laser irradiation, CuS nanoparticles induce photothermal conversion, elevating the temperature to the UCST and triggering the phase transition of the external polymer from hydrophobic to hydrophilic states. This controlled response facilitates the release of Dox from the pores of MSN. The resulting nanocarrier, featuring a synergistic combination of PTT and chemotherapy, demonstrated exceptional anti-tumor efficacy at both cellular and animal levels. [Display omitted] • A cascade response mechanism utilizing photothermal and temperature-responsive nanoplatform has been achieved. • The outer layer of UCST-type polymer on C@M@P acts as a "gatekeeper" to enable precise control over drug release kinetics. • Upon NIR laser irradiation, CuS induce photothermal conversion, triggering the phase transition of the external polymer. [ABSTRACT FROM AUTHOR]

Small extracellular vesicles (SEV) have attracted much attention both as mediators of intercellular communication and as drug delivery systems. In addition, recent studies have shown that SEV containing virus components and virus particles are released from virus-infected cells. Oncolytic viruses, which efficiently kill tumor cells by tumor cell-specific replication, have been actively studied as novel anticancer agents in clinical and preclinical studies. However, it remains to be fully elucidated whether SEV released from oncolytic virus-infected cells are involved in the antitumor effects of oncolytic viruses. In this study, we examined the tumor cell killing efficiencies and innate immune responses following treatment with SEV released from oncolytic reovirus-infected tumor cells in vitro and in vivo. Reovirus-infected B16 cells secreted SEV associated with or containing reovirus particles (Reo-SEV) with a diameter of approximately 130 nm and a zeta potential of −17 mV, although death of reovirus-infected B16 cells was not observed. The secreted Reo-SEV also contained interferon (IFN)-β, tumor antigens, and damage-associated molecular patterns (DAMPs), including heat shock proteins (HSPs). Reo-SEV were secreted from the tumor tissues of reovirus-injected mice. Inhibition of the SEV secretion pathway using GW4869, which is a neutral sphingomyelinase inhibitor, resulted in significant reduction in the infectious titers of reovirus in the culture supernatants, suggesting that the cells released progeny virus via the SEV secretion pathway. Reo-SEV more efficiently killed mouse tumor cells and induced innate immune responses in mouse bone marrow-derived dendritic cells than reovirus. Reovirus and Reo-SEV mediated efficient and comparable levels of growth suppression of B16 subcutaneous tumors and induction of tumor infiltration of CD8+ T cells following intravenous administration. These results indicate that Reo-SEV are a promising oncolytic agent and that SEV are an effective delivery vehicle for oncolytic virus. [Display omitted] • Reovirus-infected cells released the SEV associated with progeny virus particles. • Progeny virus was released by utilizing the SEV secretion pathway. • Reo-SEV contained reovirus particles, IFN-β, DAMPs, and tumor antigens. • Reo-SEV mediated efficient tumor cell killing activities. • Reo-SEV induced efficient innate immune responses. [ABSTRACT FROM AUTHOR]

We scrutinized the impact of doping of X atoms (X = Fe, Co, Ni, Cu, and Zn) on the metformin (MF) drug delivery performance of a BP nanotube (BPNT) using density functional B3LYP calculations. The pristine BPNT was not ideal for the drug delivery of MF because of a weak interaction between the drug and nanotube. Doping of the Zn, Cu, Ni, Co, and Fe into the BPNT surface raised the adsorption energy of MF from −5.3 to –29.1, −28.7, −29.8, −32.1, and −26.9 kcal/mol, respectively, demonstrating that the sensitiveness of the metal-doped BPNT increased after increasing the radius atomic of metals. Ultimately, there was an increase in the adhesion performance and capacity of the MF after X (especially Co atom) doping, making the nanotube suitable for MF drug delivery. The mechanism of MF reaction with the BPNT changed from covalent bonding in the natural environment to hydrogen bonding in the cancerous cells with high acidity. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV) is a clinically useful gene delivery vehicle for treating neurological diseases. To deliver AAV to focal targets, direct infusion into brain tissue by convection-enhanced delivery (CED) is often needed due to AAV's limited penetration across the blood-brain-barrier and its low diffusivity in tissue. In this study, computational models that predict the spatial distribution of AAV in brain tissue during CED were developed to guide future placement of infusion catheters in recurrent brain tumors following primary tumor resection. The brain was modeled as a porous medium, and material property fields that account for magnetic resonance imaging (MRI)-derived anatomical regions were interpolated and directly assigned to an unstructured finite element mesh. By eliminating the need to mesh complex surfaces between fluid regions and tissue, mesh preparation was expedited, increasing the model's clinical feasibility. The infusion model predicted preferential fluid diversion into open fluid regions such as the ventricles and subarachnoid space (SAS). Additionally, a sensitivity analysis of AAV delivery demonstrated that improved AAV distribution in the tumor was achieved at higher tumor hydraulic conductivity or lower tumor porosity. Depending on the tumor infusion site, the AAV distribution covered 3.67–70.25% of the tumor volume (using a 10% AAV concentration threshold), demonstrating the model's potential to inform the selection of infusion sites for maximal tumor coverage. [ABSTRACT FROM AUTHOR]

The gasotransmitters nitric oxide (NO) and hydrogen sulfide (H 2 S) play important roles not only in maintaining physiological functions, but also in pathological conditions and events. Importantly, these molecules show a complex interplay in cancer biology, demonstrating both tumor-promoting and anti-tumor activities depending on their concentration, flux, and the environmental redox state. Additionally, various cell types respond differently to NO and H 2 S. These gasotransmitters can be synergistically combined with traditional anticancer treatments such as radiotherapy, immunotherapy, chemotherapy, and phototherapy. Notably, NO, and more recently H 2 S, have been shown to reverse multidrug resistance. Nanomaterials to deliver NO donors and, to a lesser extent, H 2 S donors, have emerged as a promising approach for targeted delivery of these gasotransmitters. Nanotechnology has advanced the delivery of anticancer drugs, enhancing efficiency and reducing side effects on non-cancerous cells. This review highlights recent progress in the design of NO and H 2 S-releasing nanomaterials for anticancer effects. It also explores the interactions between NO and H 2 S, which are crucial for developing combined therapies and nanomedicines with minimal side effects. • This review integrates recent nitric oxide (NO) and hydrogen sulfide (H 2 S) releasing nanomaterials in cancer treatment. • Research gaps are identified where further contributions can enhance understanding of the physiological roles of NO and H 2 S. • Gaps are explored throughout, highlighting potential avenues for exploration in cancer treatment using NO and H 2 S. [ABSTRACT FROM AUTHOR]

The design, synthesis and characterization of a novel nucleoamino acid derivative based on an l-tryptophanamide functionalised with a thymine nucleobase (named TrpT) is here described. The novel construct's tendency to self-assemble into supramolecular networks in aqueous solution was demonstrated by dynamic light scattering (DLS), circular dichroism (CD), fluorescence and UV spectroscopic measurements. TrpT nanoaggregates showed good stability (up to 5 h) at 140 µM and proved to comprise species of mean hydrodynamic diameter 330 nm and a homogeneous size distribution; scanning electron microscopy (SEM) analysis further revealed these to be spherical-shaped assemblies. The ability of TrpT nanoaggregates to bind curcumin, selected as a model anticancer drug, was also evaluated and its release was monitored over time by confocal microscopy. Molecular docking studies were performed on both TrpT self-assembly and curcumin-loaded nanoaggregates suggesting that the phytomolecule can be accommodated in the interior of the supramolecular network via hydrophobic (π−π and π-alkyl) interactions; the formation of TrpT-curcumin adducts may improve the polarity of the highly-hydrophobic curcumin with a resulting logP closer to the optimal values expected for a good drug bioavailability, as estimated by the ADMETlab software. Finally, the high stability of TrpT nanoassembly in human serum, and the absence of significant toxic effects on human model cells in a cell viability assay, were also demonstrated. Despite its thymine-based scaffold, TrpT was shown not to bind adenine-bearing nucleic acids, suggesting that this interaction is hindered by its intrinsic propensity to self-assemble in preference to forming A-T base pairings. Instead, TrpT was able to interact with a serum protein such as bovine serum albumin (BSA), known to improve the bloodstream transportation and bioavailability of its cargo. Collectively, our findings support the potential use of TrpT for the development of new drug delivery systems. [ABSTRACT FROM AUTHOR]

Perfluorocarbon nanodroplets (NDs) have been widely investigated as both diagnostic and therapeutic agents. There remains, however, a challenge in generating NDs that do not vaporize spontaneously but can be activated at ultrasound pressures that do not produce unwanted bioeffects. In previous work, it has been shown that phospholipid-coated perfluorobutane (PFB) NDs can potentially overcome this challenge. The aim of this study was to investigate whether these NDs can promote drug delivery. A combination of high-speed optical imaging and passive cavitation detection was used to study the acoustic properties of the PFB-NDs in a tissue mimicking phantom. PFB-NDs were exposed to ultrasound at frequencies from 0.5 to 1.5 MHz and peak negative pressures from 0.5 to 3.5 MPa. In addition, the penetration depth of two model drugs (Nile Red and 200 nm diameter fluorescent polymer spheres) into the phantom was measured. PFB NDs were found to be stable in aqueous suspension at both 4°C and 37°C; their size remaining unchanged at 215 ± 11 nm over 24 h. Penetration of both model drugs in the phantom was found to increase with increasing ultrasound peak negative pressure and decreasing frequency and was found to be positively correlated with the energy of acoustic emissions. Extravasation depths >1 mm were observed at 0.5 MHz with pressures <1 MPa. The results of the study thus suggest that PFB NDs can be used both as drug carriers and as nuclei for cavitation to enhance drug delivery without the need for high intensity ultrasound. [ABSTRACT FROM AUTHOR]

In this work, a magnesium-based biomolecule metal organic framework (MgGA Bio-MOF) has been synthesized using magnesium chloride hexahydrate (MgCl2.6H2O) as a metal cation and an edible linker gallic acid (GA, C6H2(OH)3CO2H) as a organic building unit in water under certain experimental conditions. Initially, MgGA Bio-MOF synthesis has been confirmed through spectroscopic and microscopic analysis techniques. Afterwards, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay has been performed to know the antioxidant activity of MOF. From the DPPH assay, it has been found that MgGA Bio-MOF possesses 70.4% scavenging activity. To proceed further, the drug release studies have been performed through IBU@MgGA Bio-MOF conjugate using UV- vis spectroscopy In investigation of drug release studies, we have observed 79% IBU released up to 150 min from IBU@MgGA Bio-MOF conjugate at neutral pH. After that, a constant absorbance has been observed, indicating the complete release of IBU. Overall, we found the selected BioMOF has excellent biological utility as an antioxidant agent as well as an anti-inflammatory drug carrier in line of its real-world applications Highlights: Synthesis of MgGA Bio-MOF has been performed under certain experimental conditions. Before exploring drug delivery applications, antioxidant properties of MgGA Bio-MOF have been investigated using DPPH assay in line of biological utility evaluation. Intermolecular hydrogen bonding between IBU and Bio-MOF has been confirmed spectroscopic analysis. IBU releases studies have been performed at neutral pH. [ABSTRACT FROM AUTHOR]

Recent research has focused on the methods for administration of medications in a controlled manner while minimizing side effects. Cross-linked hydrogels have wide application area as nanocarriers. There are many approaches for developing suitable methods to produce ideal particles. Advances in microtechnology have been considered as a solution to produce controlled drug delivery systems, however, it is limited due to the necessity for specialized laboratories. In this study, a simple method to produce antibiotic-loaded chitosan particles is proposed. Production was carried out with two different designs, a syringe-based flow focusing system (outer diameter of 1 mm, inner diameter of 120 µm) and microchannel with 250 µm width and 100 µm height fabricated with the computer numerical control (CNC). Sodium Triphosphate (TPP) was used as cross-linking agent for the production of particles and the effects of the concentration and flow rates on the particle formation was investigated. It has been observed that particles can be produced in a syringe-based system, but the resulting particles are not homogeneous. In the studies carried out with CNC microchannel, it was determined by SEM analysis that the obtained particles ranged in size from 39 to 771 nm, and it was seen that the CNC microchannel was more effective at low and equal flow rates (25 µl/min). It has been found that increasing the flow rate and concentration of chitosan increases the particle size. It was determined that Ampicillin loaded particles synthesized with the CNC microchannel exhibited high inhibition against Gram positive and Gram negative bacteria. These results show that the proposed approaches for the design of microsystems can be used in the formation of drug carriers without the need for specialized laboratories and expertise. [ABSTRACT FROM AUTHOR]

Schematic illustration of the treatment and mechanism of PIOVV nanoparticles complexes target colorectal cancer Colorectal cancer is a prevalent malignancy with insidious onset and diagnostic challenges, highlighting the imperative for innovative therapeutic approaches to enhance theranostic outcomes. In this study, we elucidate the unique temperature-resistant properties of oncolytic vaccinia virus (OVV), which can synergistically target tumors under photothermal conditions. Capitalizing on this characteristic, we harness the potential of OVV by surface-loading it with indocyanine green (ICG) and encapsulating it within a platelet membrane (PLTM), resulting in the creation of PLTM-ICG-OVV (PIOVV). This innovative complex seamlessly integrates virotherapy, photodynamic therapy (PDT), and photothermal therapy (PTT). The morphology, size, dispersion stability, optical properties, and cellular uptake properties of PIOVV were evaluated by transmission electron microscopy (TEM). In vitro and in vivo experiments reveal PIOVV's remarkable specificity for cancer cells, effectively inducing apoptosis and suppressing proliferation of CT26 cell. In mouse models, PIOVV exhibits enhanced fluorescence at tumor sites, accompanied with prolonged blood circulation. Under 808 nm laser irradiation, PIOVV significantly impedes tumor growth. This pioneering strategy holds immense potential for advancing phototherapy, oncolytic virology, drug delivery, and tumor-specific targeting, particularly in the context of CRC theranostics. [Display omitted] Colorectal cancer (CRC) is a prevalent malignancy with insidious onset and diagnostic challenges, highlighting the need for therapeutic approaches to enhance theranostic outcomes. In this study, we elucidated the unique temperature-resistant properties of the oncolytic vaccinia virus (OVV), which can synergistically target tumors under photothermal conditions. To capitalize on this characteristic, we harnessed the potential of the OVV by surface-loading it with indocyanine green (ICG) and encapsulating it within a platelet membrane (PLTM), resulting in the creation of PLTM-ICG-OVV (PIOVV). This complex seamlessly integrates virotherapy, photodynamic therapy (PDT), and photothermal therapy (PTT). The morphology, size, dispersion stability, optical properties, and cellular uptake of PIOVV were evaluated using transmission electron microscopy (TEM). In vitro and in vivo experiments revealed specificity of PIOVV for cancer cells; it effectively induced apoptosis and suppressed CT26 cell proliferation. In mouse models, PIOVV exhibits enhanced fluorescence at tumor sites, accompanied by prolonged blood circulation. Under 808 nm laser irradiation, PIOVV significantly inhibited tumor growth. This strategy holds the potential for advancing phototherapy, oncolytic virology, drug delivery, and tumor-specific targeting, particularly in the context of CRC theranostics. [ABSTRACT FROM AUTHOR]

Oral aphthous ulcers are common mucosal lesions that cause pain and discomfort. There are diverse biomaterials and drug treatments for oral ulcers used in both research and clinical settings. However, the complex oral environment often results in low adhesion and short drug retention times, which lead to poor drug availability and treatment outcomes. In this study, a mussel-inspired adhesive hydrogel was developed by grafting catechol onto hyaluronic acid (C-HA), and dopamine was added for oxidative pre-polymerization to form modified hyaluronic acid (M-HA), which remarkably increased the adhesion of the hydrogels. Then, M-HA was interpenetrated into the gelatin methacryloyl (GelMA) network. Chlorhexidine gluconate (CHG) was then incorporated into the hydrogel to enhance its availability and therapeutic effect through its sustained-release capability. The GelMA/M-HA hydrogel demonstrated strong adhesion to wet tissues, antibacterial and anti-inflammatory properties, and good biocompatibility. In both rat oral ulcers and infected wounds, the adhesive hydrogel significantly accelerated the healing of the ulcers and infected wounds. These results indicated that this adhesive hydrogel offers a promising new strategy for the treatment of oral ulcers in clinical practice. Oral ulcers are a common and high-incidence mucosal condition that seriously affect people's daily lives, often making it difficult for patients to chew and speak. However, a dynamic oral environment with various types of bacteria influences drug availability and treatment effects in clinical settings. To address this challenge, an adhesive, mussel-inspired, drug-loaded hydrogel was constructed using natural macromolecules (hyaluronic acid and gelatin) with good biocompatibility. Chlorhexidine gluconate (CHG), with its broad-spectrum antibacterial activity, has been incorporated to synergistically promote oral ulcer healing. The splendid adhesion, antibacterial, and therapeutic effects of this hydrogel demonstrated a new strategy for treating oral ulcers. [Display omitted] [ABSTRACT FROM AUTHOR]

Bilateral communication between bones and muscles is essential for healing composite bone–muscle injuries from orthopedic surgeries and trauma. However, these injuries are often characterized by exaggerated inflammation, which can disrupt bone–muscle crosstalk, thereby seriously delaying the healing of either tissue. Existing approaches are largely effective at healing single tissues. However, simultaneous healing of multiple tissues remains challenging, with little research conducted to date. Here we introduce collagen patches that overcome this overlooked issue by harnessing the plasticity of macrophage phenotypes. Phosphatidylserine liposomes (PSLs) capable of shifting the macrophage phenotype from inflammatory M1 into anti-inflammatory/prohealing M2 were coated on collagen patches via a layer-by-layer method. Original collagen patches failed to improve tissue healing under inflammatory conditions coordinated by M1 macrophages. In contrast, PSL-coated collagen patches succeeded in accelerating bone and muscle healing by inducing a microenvironment dominated by M2 macrophages. In cell experiments, differentiation of preosteoblasts and myoblasts was completely inhibited by secretions of M1 macrophages but unaffected by those of M2 macrophages. RNA-seq analysis revealed that type I interferon and interleukin-6 signaling pathways were commonly upregulated in preosteoblasts and myoblasts upon stimulation with M1 macrophage secretions, thereby compromising their differentiation. This study demonstrates the benefit of PSL-mediated M1-to-M2 macrophage polarization for simultaneous bone and muscle healing, offering a potential strategy toward simultaneous regeneration of multiple tissues. Existing approaches for tissue regeneration, which primarily utilize growth factors, have been largely effective at healing single tissues. However, simultaneous healing of multiple tissues remains challenging and has been little studied. Here we demonstrate that collagen patches releasing phosphatidylserine liposomes (PSLs) promote M1-to-M2 macrophage polarization and are effective for simultaneous healing of bone and muscle. Transcriptome analysis using next-generation sequencing reveals that differentiation of preosteoblasts and myoblasts is inhibited by the secretions of M1 macrophages but promoted by those of M2 macrophages, highlighting the importance of timely regulation of M1-to-M2 polarization in tissue regeneration. These findings provide new insight to tissue healing of multiple tissues. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: Glioblastoma multiforme is a highly aggressive form of brain cancer, and early diagnosis plays a pivotal role in improving patient survival rates. In this regard, molecular magnetic resonance imaging has emerged as a promising imaging modality due to its exceptional sensitivity to minute tissue changes and the ability to penetrate deep into the brain. This study aimed to assess the efficacy of a novel contrast agent in detecting gliomas during MRI scans. Materials and methods: The contrast agent utilized modified chitosan coating on manganese oxide nanoparticles. The modification included adding methotrexate and 5-aminolevulinic acid (MnO2/CS@5-ALA-MTX) to target cells with overexpressed folate receptors and breaking down excess hydrogen peroxide in tumor tissue, resulting in enhanced signal intensity in T1-weighted MR images but diminished signal intensity in T2*-weighted MR images. Results: The nanosystem was characterized and evaluated in MR imaging, safety, and ability to target cells both in vivo and in vitro. MTX-free nanoparticles (MnO2/CS@5-ALA NPs) had no obvious cytotoxicity on cell lines U87MG and NIH3T3 after 24/48 h at a concentration of up to 160 µgr/mL (cell viability more than 80%). In this system, methotrexate enables tumor targeting and the MnO2/5-ALA improves T1–T2*-weighted MRI. In addition, MRI scans of mice with M109 carcinoma indicated significant tumor uptake and NP capacity to improve the positive contrast effect. Conclusion: This developed MnO2/CS@5-ALA-MTX nanoparticle system may exhibit great potential in the accurate diagnosis of folate receptor over-expressing cancers such as glioblastoma. [ABSTRACT FROM AUTHOR]

Immunotherapy has markedly reinvented how we treat cancer, as shown by numerous Food and Drug Administration (FDA) drug approvals that have made significant clinical impact and ongoing clinical trials. However, undesirable side effects, such as autoimmunity and inflammation, and inconsistent clinical outcomes remain a major challenge. Improving response rates across various immunotherapeutic reagents is imperative to enhance overall effectiveness and reduce adverse side effects. To address this challenge, interdisciplinary approaches have been explored by incorporating immunotherapies into hydrogels, enabling fine-controlled delivery to target tissues. This review focuses on recent progress in the utilization of hydrogel-based delivery systems for cancer immunotherapy and their potential to further enhance treatment response rates. Specifically, recent preclinical advances in hydrogels implemented with immune checkpoint inhibitors, combination therapies, and vaccines, along with self-assembled peptide hydrogels, are reviewed. We also discuss technological advances and drawbacks in this area and provide insights to ultimately realize the clinical application of hydrogels in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Controlled delivery of proteins and other biologics is a growing medium of therapy for diseases previously untreatable. Here we report a self-assembling, tunable vesicle for the controlled delivery of growth factors and cytokines. Coacervate made of heparin and a biocompatible polycation, PEAD, forms the core of the vesicle; lipids form the membrane of the vesicle. We call this vesicle lipocoacervate (LipCo), which has a high affinity for growth factors and cytokines due to heparin. LipCo is a tunable protein delivery vehicle. The vesicle size is controlled through polymer and salt concentrations. Membrane functionalization enables potential for targeting capabilities with long-term storage through lyophilization. Importantly, the controlled delivery of therapeutics also avoids high toxicity to treated cells in vitro. Here we report on these key principles of LipCo assembly and design. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a recurring chronic inflammatory disease. Current treatment strategies are aimed at alleviating clinical symptoms and are associated with gastrointestinal or systemic adverse effects. New delivery strategies are needed for the treatment of IBD. Bacteria are promising biocarriers, which can produce drugs in situ and sense the gut in real time. Herein, we focus on recent studies of engineered bacteria used for IBD treatment and introduce the application of engineered bacteria in the diagnosis. On this basis, the current dilemmas and future developments of bacterial delivery systems are discussed. [ABSTRACT FROM AUTHOR]

Recently, the field of nanomedicine has witnessed substantial advancements in the development of nanocarriers for targeted drug delivery, emerges as promising platforms to enhance therapeutic efficacy and minimize adverse effects associated with conventional chemotherapy. Notably, deformable nanocarriers have garnered considerable attention due to their unique capabilities of size changeable, tumor‐specific aggregation, stimuli‐triggered disintegration, and morphological transformations. These deformable nanocarriers present significant opportunities for revolutionizing drug delivery strategies, by responding to specific stimuli or environmental cues, enabling achieved various functions at the tumor site, including size‐shrinkage nanocarriers enhance drug penetration, aggregative nanocarriers enhance retention effect, disintegrating nanocarriers enable controlled drug release, and shape‐changing nanocarriers improve cellular uptake, allowing for personalized treatment approaches and combination therapies. This review provides an overview of recent developments and applications of deformable nanocarriers for enhancing tumor therapy, underscores the diverse design strategies employed to create deformable nanocarriers and elucidates their remarkable potential in targeted tumor therapy. [ABSTRACT FROM AUTHOR]

Self-assembly of peptide building blocks offers unique opportunities for bottom-up preparation of exquisite nanostructures, nanoarchitectures, and nanostructured bulk materials, namely hydrogels. In this work we describe the synthesis, characterization, gelation, and rheological properties of new dehydrotripeptides, Cbz-L-Lys(Cbz)-L,D-Asp-∆Phe-OH and (2-Naph)-L-Lys(2-Naph)-L,D-Asp-∆Phe-OH, containing a N-terminal lysine residue Nα,ε-bis-capped with carboxybenzyl (Cbz) and 2-Naphthylacetyl (2-Naph) aromatic moieties, an aspartic acid residue (Asp), and a C-terminal dehydrophenylalanine (∆Phe) residue. The dehydrotripeptides were obtained as diastereomeric mixtures (L,L,Z and L,D,Z), presumably via aspartimide chemistry. The dehydrotripeptides afforded hydrogels at exceedingly low concentrations (0.1 and 0.04 wt%). The hydrogels revealed exceptional elasticity (G' = 5.44 × 104 and 3.43 × 106 Pa) and self-healing properties. STEM studies showed that the diastereomers of the Cbz-capped peptide undergo co-assembly, generating a fibrillar 3D network, while the diastereomers of the 2-Naph-capped dehydropeptide seem to undergo self-sorting, originating a fibril network with embedded spheroidal nanostructures. The 2-Naph-capped hydrogel displayed full fast recovery following breakup by a mechanical stimulus. Spheroidal nanostructures are absent in the recovered hydrogel, as seen by STEM, suggesting that the mechanical stimulus triggers rearrangement of the spheroidal nanostructures into fibers. Overall, this study demonstrates that diastereomeric mixtures of peptides can be efficacious gelators. Importantly, these results suggest that the structure (size, aromaticity) of the capping group can have a directing effect on the self-assembly (co-assembly vs. self-sorting) of diastereomers. The cytotoxicity of the newly synthesized gelators was evaluated using human keratinocytes (HaCaT cell line). The results indicated that the two gelators exhibited some cytotoxicity, having a small impact on cell viability. In sustained release experiments, the influence of the charge on model drug compounds was assessed in relation to their release rate from the hydrogel matrix. The hydrogels demonstrated sustained release for methyl orange (anionic), while methylene blue (cationic) was retained within the network. [ABSTRACT FROM AUTHOR]

This study investigates the development and characterization of a novel composite hydrogel composed of polyacrylamide (PAAm), starch, and gelatin for use as an amoxicillin delivery system. The optical properties, swelling behavior, and drug release profile of the composite hydrogel's were studied to evaluate its efficacy and potential applications. UV-visible spectroscopy was employed to determine the optical properties, revealing significant transparency in the visible range, which is essential for biomedical applications. The incorporation of starch and gelatin into the polyacrylamide matrix significantly enhanced the hydrogel's swelling capacity and biocompatibility. Studies on drug delivery demonstrated a sustained release profile of amoxicillin in simulated gastrointestinal fluids, which is essential for maintaining therapeutic levels for a prolonged amount of time. The results indicate that the composite hydrogel of PAAm/starch/gelatin has good swelling behavior, appealing optical characteristics, and a promising controlled drug release mechanism. These results point to this hydrogel's considerable potential as a drug delivery method, providing a viable path toward enhancing the medicinal effectiveness of amoxicillin and maybe other medications. [ABSTRACT FROM AUTHOR]

Background: Nano-drug delivery systems have become a promising approach to overcoming problems such as low solubility and cellular uptake of drugs. Along with various delivery devices, dendrimers are widely used through their unique features. PEG-citrate dendrimers are biocompatible and nontoxic, with the ability to improve drug solubility. Curcumin, a naturally occurring polyphenol, has multiple beneficial properties, such as antiviral activities. However, its optimum potential has been significantly hampered due to its poor water solubility, which leads to reduced bioavailability. So, the present study attempted to address this issue and investigate its antiviral effects against HIV-1. Method: The G2 PEG-citrate dendrimer was synthesized. Then, curcumin was conjugated to it directly. FTIR, HNMR, DLS, and LCMS characterized the structure of products. The conjugate displayed an intense yellow color. In addition, increased aqueous solubility and cell permeability of curcumin were achieved based on flow cytometry results. So, it could be a suitable vehicle for improving the therapeutic applications of curcumin. Moreover, cell toxicity was assessed using XTT method. Ultimately, the SCR HIV system provided an opportunity to evaluate the level of HIV-1 inhibition by the curcumin-dendrimer conjugate using a p24 HIV ELISA kit. Results: The results demonstrated a 50% up to 90% inhibition of HIV proliferation at 12 μm and 60 μm, respectively. Inhibition of HIV-1 at concentrations much lower than CC50 (300 µM) indicates a high potential of curcumin-dendrimer conjugate against this virus. Conclusion: Thereby, curcumin-dendrimer conjugate proves to be a promising tool to use in HIV-1 therapy. [ABSTRACT FROM AUTHOR]

The prevention of blindness from glaucoma requires multiple treatments to lower intraocular pressure. Here, human contact lenses are modified with highly porous metal‐organic frameworks with sustained release of brimonidine for prolonged glaucoma treatment. Various metal‐organic frameworks were screened for their attachment to lenses, loading with brimonidine, and drug‐release properties. Optimized therapeutic ocular lenses conjugated with MIL‐101(Cr) frameworks maintain optical transparency and power. Coating of lenses with MIL‐101(Cr) nanoparticles reduced brimonidine washout with tears and ensured a gradual and localized release of the drug into the eyeball through the cornea. The hybrid lenses provided a 4.5‐fold better decrease in eye pressure, compared by area under the curve (AUC) value to a commercially available brimonidine tartrate solution. Therapeutic lenses did not induce any notable eye irritation or corneal damage in vivo. The newly developed hybrid lenses are expected to provide a robust platform for the therapy and prevention of various ocular diseases. [ABSTRACT FROM AUTHOR]

The good lubrication ability of articular cartilage holds significant importance in our daily lives. Osteoarthritis (OA), the most prevalent degenerative joint disease, causes cartilage damage, increased friction, and inflammation. However, the current clinical treatments for OA exhibit some defects. Recently, the sustained drug release systems with lubricating function have attracted considerable attention for treating OA. This review introduces the lubrication mechanism of cartilage, focusing particularly on the boundary lubrication mechanism. The research progress of boundary-lubricated biomaterials with drug delivery, including microcarriers, hydrogels, and nanoparticles in the treatment of OA by improving inter-articular lubrication and relieving inflammation is discussed and summarized. The efficacy and challenges of boundary-lubricated biomaterials with drug delivery in the treatment of OA are summarized, and the prospects are also discussed. [ABSTRACT FROM AUTHOR]

Using nanostructured drug delivery systems has attracted increasing interest in immunotherapeutic approaches. The intrinsic immunomodulatory properties and versatility of nanoparticles used as carriers were consistently reported to augment treatment efficiency as nanoscaled materials increase drug accumulation at the desired site, enhance cell internalization, and improve therapeutic outcomes. Thus, numerous studies have exploited the potential use of nanostructured drug delivery vehicles in delivering different cargo as a promising alternative for treating conditions like cancer, autoimmune diseases, infectious diseases, and allergic and immune disorders. In this context, this paper presents nanostructured drug delivery systems as a solid basis for immunotherapeutic innovations, highlighting their advantages for improving treatment strategies, reviewing their clinical applications, and discussing existing challenges and ways to overcome them. [ABSTRACT FROM AUTHOR]

Dendrimers, distinguished by their mono-dispersed globular or spheroid macromolecular structures with repeated branches, exhibit unique and desirable characteristics that set them apart from other polymers. These characteristics include their nanoscopic size, precise control over molecular structure, low polydispersity index, water solubility, exceptional physicochemical stability, self-assembly capabilities, polyvalency, chemical stability, electrostatic interactions, solubility, and minimal cytotoxicity. Dendrimers are prepared from monomers using either divergent or convergent step-growth polymerization. Dendrimers have the ability to reduce the toxicity of medications while enhancing their effectiveness. This review will delve into various types of dendrimers such as poly (amidoamine) dendrimers, peptide dendrimers, smart dendrimers, polyethylene glycol dendrimers, poly (propylene imine) dendrimers, polyester dendrimers, Janus dendrimers, and etc. in the field of drug delivery and gene delivery systems that utilize them. Dendrimer-drug conjugates offer numerous benefits over conventional drug carriers, such as enhanced drug uptake by the tumor, reduced systemic toxicity issues, and increased antitumor activity of the administrated medications. To achieve this objective, the authors utilized the Science Direct, PubMed, and Scopus databases to acquire the information, evaluating references individually, extracting essential details, and assessing the quality of the included studies. [ABSTRACT FROM AUTHOR]

The geometrical structures of cucurbit[n]uril (CB[n], n = 5–8 and their complexes with molnupiravir (MLP) drug have been investigated using the DFT computations. The complexation energies and electronic properties of CB[n]/MLP complexes were also computed. The host–guest interactions in the complexation are occurred through the of dipole–dipole interactions which are the hydrogen bonds between the O−H or N−H of molnupiravir and oxygen atoms of CB[n]s. The CB[n]/MLP host–guest complexation in both gas and water are found to be an exothermic reaction with negative complexation energy values. By means of the NBO analysis and MEP contours, the partial charge transfers from CB[n]s to molnupiravir are displayed. After drug complexation, the electronics properties of CB[n]s are significantly changed. This means that CB[n]s can act as a host for appropriately molnupiravir guest, even in aqueous solution. [ABSTRACT FROM AUTHOR]

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A spinal cord injury (SCI) compresses the spinal cord, killing neurons and glia at the injury site and resulting in prolonged inflammation and scarring that prevents regeneration. Astrocytes, the main glia in the spinal cord, become reactive following SCI and contribute to adverse outcomes. The anti‐inflammatory cytokine transforming growth factor beta 3 (TGFβ3) has been shown to mitigate astrocyte reactivity; however, the effects of prolonged TGFβ3 exposure on reactive astrocyte phenotype have not yet been explored. This study investigates whether magnetic core‐shell electrospun fibers can be used to alter the release rate of TGFβ3 using externally applied magnetic fields, with the eventual application of tailored drug delivery based on SCI severity. Magnetic core‐shell fibers are fabricated by incorporating superparamagnetic iron oxide nanoparticles (SPIONs) into the shell and TGFβ3 into the core solution for coaxial electrospinning. Magnetic field stimulation increased the release rate of TGFβ3 from the fibers by 25% over 7 days and released TGFβ3 reduced gene expression of key astrocyte reactivity markers by at least twofold. This is the first study to magnetically deliver bioactive proteins from magnetic fibers and to assess the effect of sustained release of TGFβ3 on reactive astrocyte phenotype. [ABSTRACT FROM AUTHOR]

Drug delivery to central nervous pathologies is compromised by the blood-brain barrier (BBB). A clinically explored strategy to promote drug delivery across the BBB is sonopermeation, which relies on the combined use of ultrasound (US) and microbubbles (MB) to induce temporally and spatially controlled opening of the BBB. We developed an advanced in vitro BBB model to study the impact of sonopermeation on the delivery of the prototypic polymeric drug carrier pHPMA as a larger molecule and the small molecule antiviral drug ribavirin. This was done under standard and under inflammatory conditions, employing both untargeted and RGD peptide-coated MB. The BBB model is based on human cerebral capillary endothelial cells and human placental pericytes, which are co-cultivated in transwell inserts and which present with proper transendothelial electrical resistance (TEER). Sonopermeation induced a significant decrease in TEER values and facilitated the trans-BBB delivery of fluorescently labeled pHPMA (Atto488-pHPMA). To study drug delivery under inflamed endothelial conditions, which are typical for e.g. tumors, neurodegenerative diseases and CNS infections, tumor necrosis factor (TNF) was employed to induce inflammation in the BBB model. RGD-coated MB bound to and permeabilized the inflamed endothelium-pericyte co-culture model, and potently improved Atto488-pHPMA and ribavirin delivery. Taken together, our work combines in vitro BBB bioengineering with MB-mediated drug delivery enhancement, thereby providing a framework for future studies on optimization of US-mediated drug delivery to the brain. [ABSTRACT FROM AUTHOR]

A monster called cancer is still one of the most challenging human problems and one of the leading causes of death in the world. Different types of treatment methods are used for cancer therapy; however, there are challenges such as high cost and harmful side effects in using these methods. Recent years have witnessed a surge in the development of therapeutic peptides for a wide range of diseases, notably cancer. Peptides are preferred over antibiotics, radiation therapy, and chemotherapy in the treatment of cancer due to a number of aspects, including flexibility, easy modification, low immunogenicity, and inexpensive cost of production. The use of therapeutic peptides in cancer treatment is a novel and intriguing strategy. These peptides provide excellent prospects for targeted drug delivery because of their high selectivity, specificity, small dimensions, good biocompatibility, and simplicity of modification. Target specificity and minimal toxicity are benefits of therapeutic peptides. Additionally, peptides can be used to design antigens or adjuvants for vaccine development. Here, types of therapeutic peptides for cancer therapy will be discussed, such as peptide-based cancer vaccines and tumor-targeting peptides (TTP) and cell-penetrating peptides (CPP). [ABSTRACT FROM AUTHOR]

Nanogels represent a significant innovation in the fields of nanotechnology and biomedical engineering, combining the properties of hydrogels and nanoparticles to create versatile platforms for drug delivery, tissue engineering, bioimaging, and other biomedical applications. These nanoscale hydrogels, typically ranging from 10 to 1000 nm, possess unique characteristics such as high water content, biocompatibility, and the ability to encapsulate both hydrophilic and hydrophobic molecules. The review explores the synthesis, structural configurations, and stimuli‐responsive nature of nanogels, highlighting their adaptability for targeted drug delivery, including across challenging barriers like the blood–brain barrier. Furthermore, the paper delves into the biomedical applications of nanogels, particularly in drug delivery systems, tissue engineering, and bioimaging, demonstrating their potential to revolutionize these fields. Despite the promising preclinical results, challenges remain in translating these technologies into clinical practice, including issues related to stability, scalability, and regulatory approval. The review concludes by discussing future perspectives, emphasizing the need for further research to optimize the properties and applications of nanogels, ultimately aiming to enhance their efficacy and safety in clinical settings. [ABSTRACT FROM AUTHOR]

Cancer is one of the major threats to human health and lives. However, effective cancer treatments remain a great challenge in clinical medicine. As a common approach for cancer treatment, chemotherapy has saved the life of millions of people; however, patients who have gone through chemotherapy often suffer from severe side effects owing to the inherent cytotoxicity of anti-cancer drugs. Stabilizing the blood concentration of an anti-cancer drug will reduce the occurrence or severity of side effects, and relies on using an appropriate drug delivery system (DDS) for achieving sustained or even on-demand drug delivery. However, this is still an unmet clinical challenge since the mainstay of anti-cancer drugs is small molecules, which tend to be diffused rapidly in the body, and conventional DDSs exhibit the burst release phenomenon. Here, we establish a class of DDSs based on biodegradable core–shell microspheres with encapsulated doxorubicin hydrochloride-loaded gold nanoparticles (DOX@Au@MSs), with the core–shell microspheres being made of poly(lactic-co-glycolic acid) in the current study. By harnessing the physical barrier of the biodegradable shell of core–shell microspheres, DOX@Au@MSs can provide a sustained release of the anti-cancer drug in the test duration (which is 21 days in the current study). Thanks to the photothermal properties of the encapsulated gold nanoparticle carriers, the core–shell biodegradable microspheres can be ruptured through remotely controlled near-infrared (NIR) light, thereby achieving an NIR-controlled triggered release of the anti-cancer drug. Furthermore, the route of the DOX-Au@MS-enabled controlled release of the anti-cancer drug can provide durable cancer cell ablation for the long period of 72 h. [ABSTRACT FROM AUTHOR]

Docetaxel (DTX) has become widely accepted as a first-line treatment for metastatic breast cancer; however, the frequent development of resistance provides challenges in treating the disease.C60 fullerene introduces a unique molecular form of carbon, exhibiting attractive chemical and physical properties. Our study aimed to develop dicarboxylic acid-derivatized C60 fullerenes as a novel DTX delivery carrier. This study investigated the potential of water-soluble fullerenes to deliver the anti-cancer drug DTX through a hydrophilic linker. The synthesis was carried out using the Prato reaction. The spectroscopic analysis confirmed the successful conjugation of DTX molecules over fullerenes. The particle size of nanoconjugate was reported to be 122.13 ± 1.63 nm with a conjugation efficiency of 76.7 ± 0.14%. The designed conjugate offers pH-dependent release with significantly less plasma pH, ensuring maximum release at the target site. In-vitro cell viability studies demonstrated the enhanced cytotoxic nature of the developed nanoconjugate compared to DTX. These synthesized nanoscaffolds were highly compatible with erythrocytes, indicating the safer intravenous route administration. Pharmacokinetic studies confirmed the higher bioavailability (~ 6 times) and decreased drug clearance from the system vis-à-vis plain drug. The histological studies reveal that nanoconjugate-treated tumour cells exhibit similar morphology to normal cells. Therefore, it was concluded that this developed formulation would be a valuable option for clinical use. [ABSTRACT FROM AUTHOR]

Curcumin (CUR) has been considered a potential therapeutic agent for allergic reactions due to its antioxidant and anti-inflammatory activities. Nanofibers have attracted increasing attention in drug delivery. The aim of this study was to investigate the combined therapeutic effects of curcumin and allergen in nanofiber-based treatments in order to increase the effectiveness of sublingual immunotherapy (SLIT) efficacy in a mouse model of allergic rhinitis. Nanofibers containing CUR (1.25% and 2.5%) and ovalbumin 2% (OVA) as an allergen were prepared via electrospinning and characterized. BALB/c mice were sensitized with OVA to the induced allergic rhinitis model. SLIT with free and/or nanofibers was carried out. IL-4, INF-γ, and IgE serum levels were measured using ELISA. Splenocyte proliferation was evaluated by the MTT assay. Lung and nasal histological examinations and nasal lavage fluid (NALF) cell counting were carried out. Nanofibers containing 1.25% CUR and 2% OVA were chosen as the optimal formulations. SLIT treatment with the CUR and OVA nanofiber co-administration led to a significantly decreased serum IgE. Nanofiber containing 2.5 µg of CUR/mouse combined with OVA nanofiber showed a significant decrease in IL-4 and an increase in IFN-γ compared to other groups. NALF assessment showed a significant decrease in specific cell and eosinophil counts in the treated nanofiber groups. The histopathological results of NAL in the optimal formulations were near normal, with diminished cellular infiltration and inflammation. Our findings suggest that co-sublingual administration of allergen and CUR nanofibers can be considered as potential immunomodulatory agents. [ABSTRACT FROM AUTHOR]

Dyslipidaemia describes the condition of abnormal lipid levels in a person's bloodstream. Since the 1980s, statin medications have been used to treat dyslipidaemia and other comorbidities, such as stroke risk and atherosclerosis. Statin medications were initially synthesised from fungal metabolites, but many synthetic statin drugs have been manufactured since then. Statin medication is quite effective in reducing total cholesterol levels in the bloodstream, but it has limitations. Due to their poor water solubility, statin drugs possess poor oral bioavailability, which hinders their therapeutic efficacy. Nanoparticle drug delivery technology has been shown to improve the pharmacokinetic profiles of many drug classes, and statins have great potential to benefit from this. This paper reviewed the currently available literature on nanoparticle statin medication and evaluated the possible improvements that can be made to the pharmacokinetic profile and efficacy of conventional statin medication. It was found that the oral bioavailability of nanoparticle medication consistently outperformed conventional medication by up to 400% in some cases. Substantial improvements in time to peak plasma concentration and plasma concentration peaks were also found, and increased periods in circulation before excretion were shown. It was concluded that nanoparticle technology has the potential to completely replace conventional statin medication as it offers more significant benefits with minimal drawbacks. Upon further study and development, the manufacture of nanoparticle statin medication should become feasible enough for large-scale application, which will significantly benefit patients and unburden healthcare systems. [ABSTRACT FROM AUTHOR]

Polymers, both synthetic and natural, play a critical role in modern drug delivery systems by enhancing the efficacy, targeting, and release profiles of therapeutic agents. This comprehensive review delves into the various types of synthetic polymers such as poly (lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and polyvinyl alcohol (PVA), as well as natural polymers like chitosan, alginate, and gelatin. These polymers are explored for their potential to improve solubility, bioavailability, and controlled release of drugs. Moreover, their application in targeted drug delivery, particularly for cancer, cardiovascular, and inflammatory diseases, is highlighted. The review also compares the advantages and limitations of synthetic versus natural polymers, discussing their biodegradability, biocompatibility, and regulatory considerations. Advances in polymer-based drug delivery platforms such as nanoparticles, hydrogels, and micelles are also examined, offering insights into future directions in personalized medicine. The highlights of provide in the review article, initially basics of drug delivery, polymer, polymerization with role of polymer in polymerization. At intermediate, classification, sources of polymer with that some advanced approached in drug delivery and lastly, marketed, recent available products with future challenges and current status in the drug delivery. [ABSTRACT FROM AUTHOR]

Gastroretentive drug delivery systems (GRDDs) have emerged as an innovative and promising approach for enhancing the bioavailability and therapeutic efficacy of drugs with narrow absorption windows in the upper gastrointestinal tract (GIT). Among various GRDDs, swellable and floating systems have garnered significant attention due to their ability to prolong gastric residence time, improve drug dissolution, and facilitate sustained drug release (SDR). This comprehensive review provides a detailed exploration of the principles, mechanisms, and advancements in swellable and floating Gastroretentive systems. The key strategies, such as the use of hydrophilic polymers, gasgenerating agents, and superporous hydrogels, are discussed. These systems offer benefits in treating conditions like peptic ulcers, gastroesophageal reflux disease, and infections, where prolonged localized drug action is desirable. A critical assessment of recent preclinical and clinical studies highlights the therapeutic potential of GRDDs in optimizing drug delivery for poorly soluble drugs and drugs with short half-lives. Challenges such as variability in gastric retention, potential toxicity of excipients, and patient-specific factors are also examined. It includes the outlining future trends in GRDDs, focusing on the incorporation of nanotechnology, 3D printing, and biocompatible materials to overcome existing limitations and further enhance therapeutic outcomes. This highlight of review article is initially introduction of GRDDs and their significance, mechanism and their classification of GRDDs, intermediately describe brief on swelling and floating GRDDs system with their application, lastly it describes the recent advances in patent, clinical trials and marketed products for GRDDs swellable and floating system. [ABSTRACT FROM AUTHOR]

Packaging hydrophobic drugs into polysaccharide carriers can improve their aqueous solubility, biocompatibility, tumor‐specific accumulation, and therapeutic effect. In this work, phenylboronic acid (PBA) was anchored onto the chain of biocompatible polysaccharide hyaluronic acid (HA) by an amide condensation reaction, which could be used to fabricate stimuli‐responsive targeted drug delivery systems. A series of pH‐responsive conjugated hyaluronic acid nanoparticles composed of a hydrophobic drug core and hydrophilic hyaluronic acid shell were prepared by the boronate‐crosslink of the PBA with diol‐containing anticancer drugs such as capecitabine (CAPE) and aloin (Al). Satisfactory targeted drug release behavior at acidic pH, lower cytotoxicity, and higher anticancer effect were realized by using this polysaccharide carrier. It is believed that this strategy has great potential for polysaccharide modification and anticancer‐associated applications. [ABSTRACT FROM AUTHOR]