Nano-drug Delivery Research Articles

Berberine-based self-assembly agents with enhanced synergistic antitumor efficacy.

Tumors are still a major threat to people worldwide. Nanodrug delivery and targeting systems can significantly improve the therapeutic efficacy of chemotherapeutic drugs for antitumor purposes. However, many nanocarriers are likely to exhibit drawbacks such as a complex preparation process, limited drug-loading capacity, untargeted drug release, and toxicity associated with nanocarriers. Therefore, new therapeutic alternatives are urgently needed to develop antitumor drugs. Natural products with abundant scaffold diversity and structural complexity, which are derived from medicinal plants, are important sources of new antitumor drugs. Here, two carrier-free berberine (BBR)-based nanoparticles (NPs) were established to increase the synergistic efficacy of tumor treatment. BBR can interact with glycyrrhetinic acid (GA) and artesunate (ART) to self-assemble BBR-GA and BBR-ART NPs without any nanocarriers, respectively, the formation of which is dominated by electrostatic and hydrophobic interactions. Moreover, BBR-GA NPs could lead to mitochondria-mediated cell apoptosis by regulating mitochondrial fission and dysfunction, while BBR-ART NPs induced ferroptosis in tumor cells. BBR-based NPs have been demonstrated to possess significant tumor targeting and enhanced antitumor properties compared with those of simple monomer mixes both in vitro and in vivo. These carrier-free self-assemblies based on natural products provide a strategy for synergistic drug delivery and thus offer broad prospects for developing enhanced antitumor drugs.

Synergistic Osteogenic and Antiapoptotic Framework Nucleic Acid Complexes Prevent Diabetic Osteoporosis

AbstractDiabetes mellitus (DM) is characterized by elevated blood glucose and advanced glycation end product (AGEs) levels. Increased AGEs in bone tissue inhibit osteogenic differentiation by bone marrow mesenchymal stem cells (BMSCs), leading to bone loss and osteoporosis in diabetic patients. Enhancing the osteogenic differentiation capacity of BMSCs in the presence of abundant AGEs can improve bone health and prevent osteoporosis in DM patients. The flavonoid, Quercetin, has anti‐inflammatory, antibacterial, and antitumor properties; however, it is insoluble in water and thus not easily absorbed by the body. Nanodrug delivery systems such as tetrahedral framework nucleic acids (tFNAs) exhibit excellent biocompatibility, efficient cell uptake, and drug piggybacking. In the present study, tFNAs with quercetin is complexed to form a novel nanodrug (tFNAs/Que) that combined the features of both components. tFNAs/Que promote osteogenic differentiation by BMSCs in an in vitro AGEs‐rich environment, maintain bone mass, and prevent diabetic osteoporosis in DM mice in vivo. The mechanism of tFNAs/Que against AGEs may be related to the JNK signaling pathway. In conclusion, it is shown that tFNAs/Que has a dual regulatory role by promoting osteogenic differentiation and inhibiting apoptosis. Such a feature is promising for the prevention and treatment of diabetic osteoporosis.

UiO-66 nanoparticles combat influenza A virus in mice by activating the RIG-I-like receptor signaling pathway

The Influenza A virus (IAV) is a zoonotic pathogen that infects humans and various animal species. Infection with IAV can cause fever, anorexia, and dyspnea and is often accompanied by pneumonia characterized by an excessive release of cytokines (i.e., cytokine storm). Nanodrug delivery systems and nanoparticles are a novel approach to address IAV infections. Herein, UiO-66 nanoparticles (NPs) are synthesized using a high-temperature melting reaction. The in vitro and in vivo optimal concentrations of UiO-66 NPs for antiviral activity are 200 μg mL−1 and 60 mg kg−1, respectively. Transcriptome analysis revealed that UiO-66 NPs can activate the RIG-I-like receptor signaling pathway, thereby enhancing the downstream type I interferon antiviral effect. These NPs suppress inflammation-related pathways, including the FOXO, HIF, and AMPK signaling pathways. The inhibitory effect of UiO-66 NPs on the adsorption and entry of IAV into A549 cells is significant. This study presents novel findings that demonstrate the effective inhibition of IAV adsorption and entry into cells via UiO-66 NPs and highlights their ability to activate the cellular RIG-I-like receptor signaling pathway, thereby exerting an anti-IAV effect in vitro or in mice. These results provide valuable insights into the mechanism of action of UiO-66 NPs against IAV and substantial data for advancing innovative antiviral nanomedicine.Graphical

18-β-Glycyrrhetinic acid encapsulated PLGA nanoparticles attenuate lung cancer proliferation and migration

Conventional treatment methods to treat lung cancer include radiation therapy, chemotherapy, and immunotherapy. However, they cause severe adverse effects and recurrence risk. 18-β-glycyrrhetinic acid (18-β-Gly), a naturally occurring bioactive compound extracted from the liquorice plant has demonstrated anticancer potential by suppressing cancer cell growth, angiogenesis, and metastasis. Although 18-β-Gly possesses potential therapeutic abilities, the application of 18-β-Gly into clinical practices is hindered due to its inferior physicochemical characteristics such as poor bioavailability and low water solubility. Poly lactic-co-glycolic acid (PLGA) is a synthetic polymer with great tuneable options for a nano-drug delivery system used for various diseases, including cancer. Formulating 18-β-Gly into PLGA has helped to overcome challenges imposed by the poor physicochemical characteristics of 18-β-Gly. For this research, 18-β-Gly-PLGA was tested for its anticancer ability using A549 human lung adenocarcinoma lines found in lung cancer. Findings showed that 18-β-Gly-PLGA has favourable physicochemical characteristics, such as sustained in vitro drug release and good entrapment efficiency. 18-β-Gly-PLGA was also able to inhibit 15% and 50% proliferation of A549 cells at 2.5 μM and 50 μM respectively and 28% inhibition of A549 cell migration at 5 μM concentration. Oncogenes such as KRT18, EGFR, BRAF and KRAS were significantly downregulated by 43%, 19.3%, 14.7% and 13.7% respectively as part of the anticancer effects and the underlying mechanism of 18-β-Gly-PLGA. Significant reduction in the expression of cancer proliferation and migration-associated proteins such as receptor tyrosine-protein kinase ErbB2, survivin, macrophage colony-stimulating factor and mesothelin was also observed. The findings of this study demonstrate the promising potential of 18-β-Gly-PLGA as a potential anticancer agent.

Recent Advances in the Treatment of Coronary Artery Disease

In the last decade, significant advancements in CAD treatment have been made. The existing treatment is medical, surgical, or a combination of both depending on the extent, severity, and clinical presentation of CAD. The collaboration between different science disciplines such as biotechnology and tissue engineering has led to the development of novel therapeutic strategies such as stem cells, nanotechnology, robotic surgery, and other advancements (3-D printing and drugs). These treatment modalities show promising effects in managing CAD and associated conditions. Research on stem cells focuses on studying the potential for cardiac regeneration, while nanotechnology research investigates nano-drug delivery and percutaneous coronary interventions including stent modifications and coatings.

Graphene oxide-supported berberine and aloe-emodin nanocomposites for dual-drug release and antimicrobial therapy

Enhanced drug resistance of Staphylococcus aureus (S. aureus) caused by antibiotic abuse brings serious safety concern. Herein, we report a nanodrug delivery strategy targeting S. aureus and achieve efficient antimicrobial therapy. First, the S. aureus-specific aptamer is conjugated with graphene oxide (GO), followed by the assembly of berberine (BBR) and aloe-emodin (AE). The combined nanodrugs with optimization ratio exhibit excellent targeted antibacterial effect on S. aureus, which is reflected by gene expressions and survival rates. Meanwhile, satisfactory safety evaluation is observed in a wide concentration range. The results of mouse mastitis model further demonstrate successful in vivo targeting of S. aureus and effective alleviation of S. aureus perfusion caused damage. This study not only provides a novel idea for the nanodrug delivery system, but also broadens the application prospect of Traditional Chinese Medicine in antimicrobial therapy.

Advances in Ferroptosis-Inducing Agents by Targeted Delivery System in Cancer Therapy.

Currently, cancer remains one of the most significant threats to human health. Treatment of most cancers remains challenging, despite the implementation of diverse therapies in clinical practice. In recent years, research on the mechanism of ferroptosis has presented novel perspectives for cancer treatment. Ferroptosis is a regulated cell death process caused by lipid peroxidation of membrane unsaturated fatty acids catalyzed by iron ions. The rapid development of bio-nanotechnology has generated considerable interest in exploiting iron-induced cell death as a new therapeutic target against cancer. This article provides a comprehensive overview of recent advancements at the intersection of iron-induced cell death and bionanotechnology. In this respect, the mechanism of iron-induced cell death and its relation to cancer are summarized. Furthermore, the feasibility of a nano-drug delivery system based on iron-induced cell death for cancer treatment is introduced and analyzed. Secondly, strategies for inducing iron-induced cell death using nanodrug delivery technology are discussed, including promoting Fenton reactions, inhibiting glutathione peroxidase 4, reducing low glutathione levels, and inhibiting system Xc-. Additionally, the article explores the potential of combined treatment strategies involving iron-induced cell death and bionanotechnology. Finally, the application prospects and challenges of iron-induced nanoagents for cancer treatment are discussed.

Exploring the Potential of Nano Drug Delivery Systems in Non-Small Cell Lung Cancer Treatment: Recent Developments and Perspectives

Abstract: Globally, lung cancer ranks among the most frequent forms of tumor. The survival rate for people suffering from lung tumors after five years is only 20%, despite novel treatment options such as immunotherapy. Current therapies cause severe off-target effects and acquired drug resistance to explain the low survival rate. Identifying and developing new therapeutic approaches for lung cancer patients is crucial to improving the standard of care. As a result of the study, we researched clinical trials and experiments in fundamental research, and new approaches to drug delivery including adenoviruses, nanoparticles, and proteolysis-targeting chimeras (PROTACs). Several approaches can now be applied directly to lung cancer to prevent disease progression, including phosphatases, targeting protein kinases, protein modifications and ubiquitin ligases. In addition, the recent approval of Ribonucleic acid (RNA) based vaccines based on lipid nanoparticle technology has made it possible to improve current lung cancer treatments by combining chemo- and immunotherapies. This review emphasises recent advancements in pharmaceutical research aimed at developing technologies to target post-translational modifications in lung tumorigenesis. Elucidation of various scientific advances in conjunction with encouraging findings concerning therapies available, the future perspectives and challenges of nanocarriers for effective lung cancer are also presented in this article.

Emerging Drug Delivery Vectors: Engineering of Plant-Derived Nanovesicles and Their Applications in Biomedicine.

Extracellular vesicles can transmit intercellular information and transport biomolecules to recipient cells during various pathophysiological processes in the organism. Animal cell exosomes have been identified as potential nanodrugs delivery vehicles, yet they have some shortcomings such as high immunogenicity, high cytotoxicity, and complicated preparation procedures. In addition to exosomes, plant-derived extracellular vesicles (PDVs), which carry a variety of active substances, are another promising nano-transport vehicles emerging in recent years due to their stable physicochemical properties, wide source, and low cost. This work briefly introduces the collection and characterization of PDVs, then focuses on the application of PDVs as natural or engineered drug carriers in biomedicine, and finally discusses the development and challenges of PDVs in future applications.

Nano-Drug Delivery Systems Targeting CAFs: A Promising Treatment for Pancreatic Cancer.

Currently, pancreatic cancer (PC) is one of the most lethal malignant tumors. PC is typically diagnosed at a late stage, exhibits a poor response to conventional treatment, and has a bleak prognosis. Unfortunately, PC's survival rate has not significantly improved since the 1960s. Cancer-associated fibroblasts (CAFs) are a key component of the pancreatic tumor microenvironment (TME). They play a vital role in maintaining the extracellular matrix and facilitating the intricate communication between cancer cells and infiltrated immune cells. Exploring therapeutic approaches targeting CAFs may reverse the current landscape of PC therapy. In recent years, nano-drug delivery systems have evolved rapidly and have been able to accurately target and precisely release drugs with little or no toxicity to the whole body. In this review, we will comprehensively discuss the origin, heterogeneity, potential targets, and recent advances in the nano-drug delivery system of CAFs in PC. We will also propose a novel integrated treatment regimen that utilizes a nano-drug delivery system to target CAFs in PC, combined with radiotherapy and immunotherapy. Additionally, we will address the challenges that this regimen currently faces.

Fabrication of hyaluronic acid-altered gold complex delivery for head and neck squamous cell carcinoma therapy with high antitumor efficacy and low in vivo toxicity

The use of multifunctional nanomedicines in the treatment of tumors is gaining popularity. Here, we constructed a nanodrug delivery system (HA/Au-PDA@CZT) that targets tumors and responds to pH and near-infrared (NIR) dual stimuli. By precisely interacting with an overexpressed CD44 receptor in specific cancer cells, hyaluronic acid (HA) is coated on the Au-PDA NP surface for tumor-targeting abilities. When exposed to NIR radiation, polydopamine (PDA) and gold nanoshells exhibit exceptional photothermal performance that has the potential to both accelerate and kill HLAC 78 head and neck squamous cell carcinoma cells. Antitumor investigations conducted in vivo and in vitro demonstrated that nanomedicine had remarkable synergistic benefits with chemotherapy and photothermal treatment. Only 25.2% of the cells in the HA/Au-PDA@CZT with a NIR irradiation group were viable. Any group's lowest tumor volume was shown in the tumor mice subjected to HA/Au-PDA@CZT with NIR at 0.3 ± 0.1. Consequently, for synergistic chemo-photothermal therapy, our logically designed nanoplatform would be the potential for a head and neck squamous tumor-targeting drug delivery system.

Impact Evaluations of Articles in Current Drug Delivery based on Web of Science.

A total of 1534 and 308 articles were published in the journal Current Drug Delivery (CDD), from 2004 and 2019 to 2021, respectively. In this commentary, their impacts were analyzed based on search data about citation times in the Web of Science. These publications were categorized from different standpoints and evaluated in terms of their citations, particularly in the year 2021. The thematic, contemporary, and local features of these articles, as well as the article types and publication formats, were interpreted. Results demonstrated that CDD should be loyal to the contents about drug delivery, particularly nano-drug delivery systems and nano-pharmaceutical technologies. Publications from the developing and developed countries and regions showed no remarkable differences; therefore, submissions are similarly welcomed. Research articles and review articles are the main stream of CDD. The ratio of review papers is about 30%, which is reasonable but should not be further extended. Moreover, open publications with an article processing charge always have a high impact than those with subscription.

Targeted Delivery of Mesenchymal Stem Cell-Derived Bioinspired Exosome-Mimetic Nanovesicles with Platelet Membrane Fusion for Atherosclerotic Treatment.

Accumulating evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes hold significant potential for the treatment of atherosclerosis. However, large-scale production and organ-specific targeting of exosomes are still challenges for further clinical applications. This study aims to explore the targeted efficiency and therapeutic potential of biomimetic platelet membrane-coated exosome-mimetic nanovesicles (P-ENVs) in atherosclerosis. To produce exosome-mimetic nanovesicles (ENVs), MSCs were successively extruded through polycarbonate porous membranes. P-ENVs were engineered by fusing MSC-derived ENVs with platelet membranes and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. The stability and safety of P-ENVs were also assessed. The targeted efficacy of P-ENVs was evaluated using an in vivo imaging system (IVIS) spectrum imaging system and immunofluorescence. Histological analyses, Oil Red O (ORO) staining, and Western blot were used to investigate the anti-atherosclerotic effectiveness of P-ENVs. Both ENVs and P-ENVs exhibited similar characteristics to exosomes. Subsequent miRNA sequencing of P-ENVs revealed their potential to mitigate atherosclerosis by influencing biological processes related to cholesterol metabolism. In an ApoE-/- mice model, the intravenous administration of P-ENVs exhibited enhanced targeting of atherosclerotic plaques, resulting in a significant reduction in lipid deposition and necrotic core area. Our in vitro experiments showed that P-ENVs promoted cholesterol efflux and reduced total cholesterol content in foam cells. Further analysis revealed that P-ENVs attenuated intracellular cholesterol accumulation by upregulating the expression of the critical cholesterol transporters ABCA1 and ABCG1. This study highlighted the potential of P-ENVs as a novel nano-drug delivery platform for enhancing drug delivery efficiency while concurrently mitigating adverse reactions in atherosclerotic therapy.

The Emerging Roles of Nanocarrier Drug Delivery System in Treatment of Intervertebral Disc Degeneration-Current Knowledge, Hot Spots, Challenges and Future Perspectives.

Low back pain (LBP) is a common condition that has substantial consequences on individuals and society, both socially and economically. The primary contributor to LBP is often identified as intervertebral disc degeneration (IVDD), which worsens and leads to significant spinal problems. The conventional treatment approach for IVDD involves physiotherapy, drug therapy for pain management, and, in severe cases, surgery. However, none of these treatments address the underlying cause of the condition, meaning that they cannot fundamentally reverse IVDD or restore the mechanical function of the spine. Nanotechnology and regenerative medicine have made significant advancements in the field of healthcare, particularly in the area of nanodrug delivery systems (NDDSs). These approaches have demonstrated significant potential in enhancing the efficacy of IVDD treatments by providing benefits such as high biocompatibility, biodegradability, precise drug delivery to targeted areas, prolonged drug release, and improved therapeutic results. The advancements in different NDDSs designed for delivering various genes, cells, proteins and therapeutic drugs have opened up new opportunities for effectively addressing IVDD. This comprehensive review provides a consolidated overview of the recent advancements in the use of NDDSs for the treatment of IVDD. It emphasizes the potential of these systems in overcoming the challenges associated with this condition. Meanwhile, the insights and ideas presented in this review aim to contribute to the advancement of precise IVDD treatment using NDDSs.

Neutrophil Extracellular Traps in Tumors and Potential Use of Traditional Herbal Medicine Formulations for Its Regulation.

Neutrophil extracellular traps (NETs) are extracellular fibers composed of deoxyribonucleic acid (DNA) and decorated proteins produced by neutrophils. Recently, NETs have been associated with the development of many diseases, including tumors. Herein, we reviewed the correlation between NETs and tumors. In addition, we detailed active compounds from traditional herbal medicine formulations that inhibit NETs, related nanodrug delivery systems, and antibodies that serve as "guiding moieties" to ensure targeted delivery to NETs. Furthermore, we discussed the strategies used by pathogenic microorganisms to evade NETs.

Recent Trends in Nano Drug Delivery Systems to Treat Cancers: With Special Focus on Liposomal Drug Delivery Systems

Cancer treatment is an area of ongoing concern and requires a great deal of research in order to provide patients and providers with the best possible therapeutic options

Simple preparation and greatly improved oral bioavailability: The supersaturated drug delivery system of quercetin based on PVP K30.

Quercetin, as a representative flavonoid, is widely present in daily diet and has been developed as a dietary supplement due to its beneficial physiological activities. However, the application of quercetin is limited due to its poor water solubility and extensive metabolism. So far, the nano-drug delivery systems designed to improve its bioavailability generally have the shortcomings of low drug loading content and difficulty in industrial production. In order to tackle these problems, quercetin supersaturated drug delivery system (QSDDS) was successfully prepared using solvent method, for which PVP K30 was employed as a crystallization and precipitation inhibitor to maintain the supersaturated state of quercetin in aqueous system. The obtained QSDDS, with a relative high drug loading content of 13%, could quickly disperse in water and form colloidal system with the mean particle size of about 200nm, meanwhile induce the generation of supersaturated quercetin solution more than 12h. In vivo pharmacokinetic study proved that QSDDS achieved a high absolute bioavailability of 36.05%, 10 times as that of physical quercetin suspension, which was dose-dependent with higher bioavailability at higher dose. Considering the simple preparation method, QSDDS provided a feasible strategy and a simple way to improve oral absorption of insoluble flavonoids.

Inhibition of growth of hepatocellular carcinoma by co-delivery of anti-PD-1 antibody and sorafenib using biomimetic nano-platelets

BackgroundTraditional nanodrug delivery systems have some limitations, such as eliciting immune responses and inaccuracy in targeting tumor microenvironments.Materials and methodsTargeted drugs (Sorafenib, Sora) nanometers (hollow mesoporous silicon, HMSN) were designed, and then coated with platelet membranes to form aPD-1-PLTM-HMSNs@Sora to enhance the precision of drug delivery systems to the tumor microenvironment, so that more effective immunotherapy was achieved.ResultsThese biomimetic nanoparticles were validated to have the same abilities as platelet membranes (PLTM), including evading the immune system. The successful coating of HMSNs@Sora with PLTM was corroborated by transmission electron microscopy (TEM), western blot and confocal laser microscopy. The affinity of aPD-1-PLTM-HMSNs@Sora to tumor cells was stronger than that of HMSNs@Sora. After drug-loaded particles were intravenously injected into hepatocellular carcinoma model mice, they were demonstrated to not only directly activate toxic T cells, but also increase the triggering release of Sora. The combination of targeted therapy and immunotherapy was found to be of gratifying antineoplastic function on inhibiting primary tumor growth.ConclusionsThe aPD-1-PLTM-HMSNs@Sora nanocarriers that co-delivery of aPD-1 and Sorafenib integrates unique biomimetic properties and excellent targeting performance, and provides a neoteric idea for drug delivery of personalized therapy for primary hepatocellular carcinoma (HCC).

Ciprofloxacin loaded PEG coated ZnO nanoparticles with enhanced antibacterial and wound healing effects

Antimicrobial resistance is a worldwide health problem that demands alternative antibacterial strategies. Modified nano-composites can be an effective strategy as compared to traditional medicine. The current study was designed to develop a biocompatible nano-drug delivery system with increased efficacy of current therapeutics for biomedical applications. Zinc oxide nanoparticles (ZnO-NPs) were synthesized by chemical and green methods by mediating with Moringa olifera root extract. The ZnO–NPs were further modified by drug conjugation and coating with PEG (CIP-PEG-ZnO-NPs) to enhance their therapeutic potential. PEGylated ZnO-ciprofloxacin nano-conjugates were characterized by Fourier Transform Infrared spectroscopy, X-ray diffractometry, and Scanning Electron Microscopy. During antibacterial screenings chemically and green synthesized CIP-PEG-ZnO-NPs revealed significant activity against clinically isolated Gram-positive and Gram-negative bacterial strains. The sustainable and prolonged release of antibiotics was noted from the CIP–PEG conjugated ZnO-NPs. The synthesized nanoparticles were found compatible with RBCs and Baby hamster kidney cell lines (BHK21) during hemolytic and MTT assays respectively. Based on initial findings a broad-spectrum nano-material was developed and tested for biomedical applications that eradicated Staphylococcus aureus from the infectious site and showed wound-healing effects during in vivo applications. ZnO-based nano-drug carrier can offer targeted drug delivery, and improved drug stability and efficacy resulting in better drug penetration.

PH-responsive supramolecular nanoparticles constructed by Cationic Pillar[5]arenes were used for drug delivery to enhance antitumor activity

ABSTRACT Nano-drug delivery systems have been widely used in antitumor therapy due to their good biocompatibility and low toxicity. However, improving drug-carrying properties and drug release from carriers remains a challenge. In this study, we successfully constructed pH-responsive supramolecular drug-carrying spherical nanoparticles by self-assembling D-alanine-modified water-soluble cationic pillar[5]arene (DAP5) and sodium laurate (SL) to form complexes in aqueous solution. The results demonstrated that DAP5 spherical nanoparticles loaded with doxorubicin hydrochloride (DOX HCl) exhibited an encapsulation rate of 60.0% and a drug loading capacity of 10.5%. These nanoparticles continuously released the drug in a weakly acidic environment that simulates tumour cells. Furthermore, SL⊂DAP5 exhibited good biocompatibility with human normal liver cells (L-02) (IC50 >10 μmol/L), while DOX⊂SL⊂DAP5 demonstrated stronger cytotoxicity against four tumour cells (Hela, HepG2, MGC-803, T-24) compared to free DOX. Notably, DOX⊂SL⊂DAP5 showed an IC50 of only 1.04 μM for HepG2 cells, which was approximately 30.32% of that of DOX (3.43 μM) after 24 hours of incubation. These findings provide valuable insights for the future development of supramolecular drug delivery systems, aiming to enhance drug utilisation and reduce toxic side effects in tumour treatment.