Nanomaterial-based Drug Delivery Research Articles

Nanomaterial-based drug delivery systems as promising carriers for patients with COVID-19.

Once the World Health Organization (WHO) declared the COVID-19 outbreak to be pandemic, massive efforts have been launched by researchers around the globe to combat this emerging infectious disease. Here we review the most recent data on the novel SARS-CoV-2 pathogen. We analyzed its etiology, pathogenesis, diagnosis, prevention, and current medications. After that, we summarized the promising drug delivery application of nanomaterial-based systems. Their preparation routes, unique advantages over the traditional drug delivery routes and their toxicity though risk analysis were also covered. We also discussed in detail the mechanism of action for one example of drug-loaded nanomaterial drug delivery systems (Avigan-contained nano-emulsions). This review provides insights about employing nanomaterial-based drug delivery systems for the treatment of COVID-19 to increase the bioavailability of current drugs, reducing their toxicity, and to increase their efficiency.

Glutathione-triggered non-template synthesized porous carbon nanospheres serve as low toxicity targeted delivery system for cancer multi-therapy

Nanomaterial based drug delivery system have received great attention in clinical application due to their high therapeutic efficacy and lower side effects than classical method, multi-functional nanomaterial also have shown the excellent performance at cancer theranostic and durg tracking in vivo and in vitro. However, most of these works are influenced by the bio-toxicity of applied nanomaterials, which could influence the diagnostic results and treatment effect. Therefore, we have prepared a high biocompatibility porous carbon nanospheres (PCNs) based nano-system (PCN-siRNA-DOX-FA) for targeted drug delivery and theranostic. The surface modifications have increased dispersion and stability of the PCNs, and folic acid (FA) had enhanced the active target ability for FA receptor positive cell lines. Moreover, through the siRNA structure and doxorubicin (DOX) loading, biological and chemical combined multi-therapy was achieved in cancerous cells. This constructed nano-system could positively improve the biotoxicity problem of nanomaterial and provide a potential platform for clinical cancer theranostic applications.

Drug-Integrating Amphiphilic Nanomaterial Assemblies: 1. Spatiotemporal control of cyclosporine delivery and activity using nanomicelles and nanofibrils

Immunomodulatory therapies are limited by unavoidable side effects as well as poor solubility, stability, and pharmacokinetic properties. Nanomaterial-based drug delivery may overcome these limitations by increasing drug solubility, site-targeting, and duration of action. Here, we prepared innovative drug-integrating amphiphilic nanomaterial assemblies (DIANA) with tunable hydrophobicity, size, and morphology, and we evaluated their ability to deliver cyclosporine A (CsA) for immunomodulatory applications. We synthesized amphiphilic block copolymers made of poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) and poly(ethylene glycol)-oligo(ethylene sulfide) (PEG-OES) that can self-assemble into solid core nanomicelles (nMIC, with ≈20 nm diameter) and nanofibrils (nFIB, with ≈5 nm diameter and > 500 nm length), respectively. nMIC and nFIB displayed good CsA encapsulation efficiency (up to 4.5 and 2 mg/mL, respectively in aqueous solution), superior to many other solubilization methods, and provided sustained release (>14 and > 7 days for the nMIC and nFIB) without compromising CsA's pharmacological activity. Treatment of insulin-secreting cells with unloaded DIANAs did not impair cell viability and functionality. Both CsA-loaded DIANAs inhibited the proliferation and activation of insulin-reactive cytotoxic T cells in vitro. Subcutaneous injections of CsA-loaded DIANAs in mice provided CsA sustained release, decreasing alloantigen-induced immune responses in the draining lymph node at lower doses and reduced administration frequency than unformulated CsA. While nMIC solubilized higher amounts and provided more sustained release of CsA in vitro, nFIB enhanced cellular uptake and promoted local retention due to slower trafficking in vivo. DIANAs provide a versatile platform for a local immune suppression regimen that can be applied to allogeneic cell transplantation.

Guidelines for the experimental design of pharmacokinetic studies with nanomaterials in preclinical animal models

A shared feature in the value proposition of every nanomaterial-based drug delivery systems is the desirable improvement in the disposition (or ADME) and pharmacokinetic profiles of the encapsulated drug being delivered. Remarkable progress has been made towards understanding the complex and multifactorial relationships between pharmacokinetic profiles and nanomaterial physicochemical properties, biological interactions, species physiology, etc. These advances have fuelled the rational design of numerous nanomaterials with long-circulation times and improved tissue accumulation (e.g., in tumours). Unfortunately, a central weakness in many of these research efforts has been the inconsistent and insufficient characterisation of the pharmacokinetic profiles of nanomaterials in scientific reporting—a problem affecting the majoirty of of contemporary nanomaterials literature and innovative nanomaterials in early stages of preclinical development especially. Given the significant role of pharmacokinetic assessments to serve as guideposts for deciding whether to continue with the preclinical development and clinical translation of drug delivery systems, the prevalence of poor pharmacokinetic characterisations in nanomaterials research is particularly alarming. A conspicuous problem in many reports is the inappropriate selection of experimental designs and methodologies for studying nanomaterial pharmacokinetics, the consequences of which are increased uncertainty over the accurate interpretation of reported pharmacokinetic data and diminished experimental reproducibility throughout the field. Thus, there is renewed interest in the establishment of consistent and comprehensive strategies for designing preclinical experiments to assess the pharmacokinetics of nanomaterials with diverse physicochemical properties. Towards this end, herein are proposed simple guidelines for the experimental design of pharmacokinetic studies with nanomaterials drawn from the best research practices, principle strategies, and important considerations used in industry for collecting pharmacokinetic data in preclinical animal models. Specifically, key experimental design factors in these studies are identified and examined in the context of nanomaterials for optimality, including blood sampling strategy and technique, sample allocation and sampling time window, test species selection, experimental sources of pharmacokinetic variability, etc. Methods for noninvasive imaging-derived pharmacokinetic assessments of theranostic nanomaterials are also explored with particular focus on emission tomography imaging modalities. Taken together, this review will provide nanomaterial researchers with practical knowledge and pragmatic recommendations for selecting the best designs and methodologies for assessing the pharmacokinetic profiles of their nanomaterials, and hopefully maximise the chances of translational success of these innovative products into humans.

Nanomaterial based drug delivery systems for the treatment of neurodegenerative diseases.

With an aging population that has been increasing in recent years, the need for the development of therapeutic approaches for treatment of neurodegenerative disorders (ND) has increased. ND, which are characterized by the progressive loss of the structure or function of neurons, are often associated with neuronal death. In spite of screening numerous drugs, currently there is no specific treatment that can cure these diseases or slow down their progression. Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Huntington's disease, and prion diseases belong to ND which affect enormous numbers of people globally. There are some main possible reasons for failure in the treatment of neurodegenerative diseases such as limitations introduced by the Blood-Brain Barrier (BBB), the Blood-Cerebrospinal Fluid Barrier (BCFB) and P-glycoproteins. Current advances in nanotechnology present opportunities to overcome the mentioned limitations by using nanotechnology and designing nanomaterials improving the delivery of active drug candidates. Some of the basic and developing strategies to overcome drug delivery impediments are the local delivery of drugs, receptor-mediated transcytosis, physicochemical disruption of the BBB, cell-penetrating peptides and magnetic disruption. Recently, the application of nanoparticles has been developed to improve the efficiency of drug delivery. Nanoengineered particles as nanodrugs possess the capacity to cross the BBB and also show decreased invasiveness. Examples include inorganic, magnetic, polymeric and carbonic nanoparticles that have been developed to improve drug delivery efficiency. Despite numerous papers published in this filed, there are some unsolved issues that need to be addressed for successful treatment of neurodegenerative diseases. These are discussed herein.

Dual Mass Spectrometric Tissue Imaging of Nanocarrier Distributions and Their Biochemical Effects

Nanomaterial-based drug delivery vehicles are able to deliver therapeutics in a controlled, targeted manner. Currently, however, there are limited analytical methods that can detect both nanomaterial distributions and their biochemical effects concurrently. In this study, we demonstrate that matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI) can be used together to obtain nanomaterial distributions and biochemical consequences. These studies employ nanoparticle-stabilized capsules (NPSCs) loaded with siRNA as a testbed. MALDI-MSI experiments on spleen tissues from intravenously injected mice indicate that NPSCs loaded with anti-TNF-α siRNA cause changes to the lipid composition in white pulp regions of the spleen, as anticipated, based on pathways known to be affected by TNF-α, whereas NPSCs loaded with scrambled siRNA do not cause the predicted changes. Interestingly, LA-ICP-MSI experiments reveal that the NPSCs primarily localize in the red pulp, suggesting that the observed changes in lipid composition are due to diffusive rather than localized effects on TNF-α production. Such information is only accessible by combining data from the two modalities, which we accomplish by using the heme signals from MALDI-MSI and iron signals from LA-ICP-MSI to overlay the images. Several unexpected changes in lipid composition also occur in regions where the NPSCs are found, suggesting that the NPSCs themselves can influence tissue biochemistry as well.

Recent advancements in two‐dimensional nanomaterials for drug delivery

Different from conventional zero-dimensional (0D) and one-dimensional (1D) counterparts, two-dimensional (2D) nanomaterials show unique properties resulting from their specific structure and morphology. In recent years, broad interest has been focused on the exploration of 2D nanomaterials for drug delivery, which benefits greatly to various disease treatments due to the superior properties of 2D nanomaterials. The fast development of 2D-based drug delivery systems provides great potential for biomedical studies. In this review, a case-by-case analysis was carried out on the state-of-the-art 2D nanomaterials-based drug delivery systems, which possesses great significance to the further biomedical development of 2D nanomaterials. For the purpose of discussing the special advantages of these novel drug delivery systems, this review is organized according to the different types of the latest 2D nanomaterials and their loading capacity towards various cargos. Special emphasis will be located on the application of these 2D nanomaterials-based drug delivery systems in chemotherapy, gene therapy, and immunotherapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Porphyrin-like porous nanomaterials as drug delivery systems for ibuprofen drug

In recent years, nanomaterial-based drug delivery carriers have become some of the most attractive to be studied. The purpose of this study is to investigate the interaction of C60 fullerene, carbon nanotube and graphene having porphyrin-like FeN4 clusters with a non-steroidal anti-inflammatory drug (ibuprofen) by means of the density functional theory. Results showed that the graphene with FeN4 clusters could remarkably increase the tendency of graphene for adsorption of ibuprofen drug. Also, our ultraviolet–visible results show that the electronic spectra of the complexes exhibit a blue shift toward lower wavelengths (higher energies). It was found that Ibp/FeN4-graphene had high chemical reactivity, which was important for binding of the drug onto the target site. In order to go further and gain insight into the binding features of considered systems with ibuprofen drug, the Atoms in Molecules analysis was performed. Our results determine the electrostatic features of the Ibp/FeN4-graphene bonding. Consequently, the results demonstrated that the FeN4-graphene could be used as potential carriers for the delivery of ibuprofen drug.

Inhalable nanotherapeutics to improve treatment efficacy for common lung diseases.

Respiratory illnesses are prevalent around the world, and inhalation-based therapies provide an attractive, noninvasive means of directly delivering therapeutic agents to their site of action to improve treatment efficacy and limit adverse systemic side effects. Recent trends in medicine and nanoscience have prompted the development of inhalable nanomedicines to further enhance effectiveness, patient compliance, and quality of life for people suffering from lung cancer, chronic pulmonary diseases, and tuberculosis. Herein, we discuss recent advancements in the development of inhalable nanomaterial-based drug delivery systems and analyze several representative systems to illustrate their key design principles that can translate to improved therapeutic efficacy for prevalent respiratory diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease.

Microfluidic-Based Platform for the Evaluation of Nanomaterial-Mediated Drug Delivery: From High-Throughput Screening to Dynamic Monitoring.

Nanomaterial-based drug delivery holds tremendous promise for improving targeting capacity, biodistribution, and performance of therapeutic/diagnostic agents. Accelerating the clinical translation of current nanomedicine requires an in-depth understanding of the mechanism underlying the dynamic interaction between nanomaterials and cells in a physiological/pathophysiological-relevant condition. The introduction of the advanced microfluidic platform with miniaturized, well-controlled, and high-throughput features opens new investigation and application opportunities for nanomedicine evaluation. This review highlights the current state-of-theart in the field of 1) microfluidic-assisted in vitro assays that are capable of providing physiological-relevant flow conditions and performing high-throughput drug screening, 2) advanced organ-on-a-chip technology with the combination of microfabrication and tissue engineering techniques for mimicking microenvironment and better predicting in vivo response of nanomedicine, and 3) the integration of microdevice with various detection techniques that can monitor cell-nanoparticle interaction with high spatiotemporal resolution. Future perspectives regarding optimized on-chip disease modeling and personalized nanomedicine screening are discussed towards further expanding the utilization of the microfluidic-based platform in assessing the biological behavior of nanomaterials.

Bacterial Biofilm Bioinspired Persistent Luminescence Nanoparticles with Gut-Oriented Drug Delivery for Colorectal Cancer Imaging and Chemotherapy.

Colorectal cancer (CRC) is now one of the leading causes of cancer incidence and mortality. Although nanomaterial-based drug delivery has been used for the treatment of colorectal cancer, inferior targeting ability of existing nanocarriers leads to inefficient treatment and side effects. Moreover, the majority of intravenously administered nanomaterials aggregate into the reticuloendothelial system, leaving a certain hidden risk to human health. All those problems gave great demands for further construction of well-performed and biocompatible nanomaterials for in vivo theranostics. In the present work, from a biomimetic point of view, Lactobacillus reuteri biofilm (LRM) was coated on the surface of trackable zinc gallogermanate (ZGGO) near-infrared persistent luminescence mesoporous silica to create the bacteria bioinspired nanoparticles (ZGGO@SiO2@LRM), which hold the inherent capability of withstanding the digestion of gastric acid and targeted release 5-FU to colorectum. Through the background-free persistent luminescence bioimaging of ZGGO, the coating of LRM facilitated the localization of ZGGO@SiO2@LRM to the tumor area of colorectum for more than 24 h after intragastric administration. Furthermore, ZGGO@SiO2@LRM hardly entered the blood, which avoided possible damage to immune organs such as the liver and spleen. In vivo chemotherapy experiment demonstrated the number of tumors per mouse in ZGGO@SiO2@LRM group decreased by one-half compared with the 5-FU group (P < 0.001). To sum up, this LRM bioinspired nanoparticles could tolerate the digestion of gastric acid, avoid aggregation by the immune system, favor gut-oriented drug delivery, and targeted release oral 5-FU into colorectum for more than 24 h, which may give new application prospects for targeted delivery of oral drugs into the colorectum.

Two-dimensional nanosheets with high curcumin loading content for multimodal imaging-guided combined chemo-photothermal therapy

Nowadays, two-dimensional (2D) nanomaterials with many fascinating physicochemical properties have drawn extensive attention as drug delivery platforms for cancer theranostics. Nevertheless, current existing 2D nanomaterial-based drug delivery systems normally undergo the bottlenecks of hash preparation process, low drug loading content and unsatisfactory therapeutic outcome. Herein, we developed a novel nanoparticles-induced assemble strategy to construct 2D nanosheets with ultra-high curcumin loading content of 59.6 % and excellent stability in water. Furthermore, a distinct photothermal effect and multimodal imaging property after polydopamine coating could be obtained, thereby leading to precise and efficient ablation of tumor in combination of curcumin-induced chemotherapy. More importantly, the design principle of our work offers novel facile strategy to assemble metal-binding drugs into 2D nanomedicine with high drug content and well-defined shapes.

Improved Healing of Diabetic Foot Ulcer upon Oxygenation Therapeutics through Oxygen-Loading Nanoperfluorocarbon Triggered by Radial Extracorporeal Shock Wave.

Diabetic foot ulcers (DFUs), the most serious complication of diabetes mellitus, can induce high morbidity, the need to amputate lower extremities, and even death. Although many adjunctive strategies have been applied for the treatment of DFUs, the low treatment efficiency, potential side effects, and high cost are still huge challenges. Recently, nanomaterial-based drug delivery systems (NDDSs) have achieved targeted drug delivery and controlled drug release, offering great promises in various therapeutics for diverse disorders. Additionally, the radial extracorporeal shock wave (rESW) has been shown to function as a robust trigger source for the NDDS to release its contents, as the rESW harbors a potent capability in generating pressure waves and in creating the cavitation effect. Here, we explored the performance of oxygen-loaded nanoperfluorocarbon (Nano-PFC) combined with the rESW as a treatment for DFUs. Prior to in vivo assessment, we first demonstrated the high oxygen affinity in vitro and great biocompatibility of Nano-PFC. Moreover, the rESW-responsive oxygen release behavior from oxygen-saturated Nano-PFC was also successfully verified in vitro and in vivo. Importantly, the wound healing of DFUs was significantly accelerated due to improved blood microcirculation, which was a result of rESW therapy (rESWT), and the targeted release of oxygen into the wound from oxygen-loaded Nano-PFC, which was triggered by the rESW. Collectively, the oxygen-saturated Nano-PFC and rESW provide a completely new approach to treat DFUs, and this study highlights the advantages of combining nanotechnology with rESW in therapeutics.

Spotlight on 17‐AAG as an Hsp90 inhibitor for molecular targeted cancer treatment

Hsp90 is a ubiquitous chaperone with important roles in the organization and maturation of client proteins that are involved in the progression and survival of cancer cells. Multiple oncogenic pathways can be affected by inhibition of Hsp90 function through degradation of its client proteins. That makes Hsp90 a therapeutic target for cancer treatment. 17-allylamino-17-demethoxy-geldanamycin (17-AAG) is a potent Hsp90 inhibitor that binds to Hsp90 and inhibits its chaperoning function, which results in the degradation of Hsp90's client proteins. There have been several preclinical studies of 17-AAG as a single agent or in combination with other anticancer agents for a wide range of human cancers. Data from various phases of clinical trials show that 17-AAG can be given safely at biologically active dosages with mild toxicity. Even though 17-AAG has suitable pharmacological potency, its low water solubility and high hepatotoxicity could significantly restrict its clinical use. Nanomaterials-based drug delivery carriers may overcome these drawbacks. In this paper, we review preclinical and clinical research on 17-AAG as a single agent and in combination with other anticancer agents. In addition, we highlight the potential of using nanocarriers and nanocombination therapy to improve therapeutic effects of 17-AAG.

Nano-Gold Loaded with Resveratrol Enhance the Anti-Hepatoma Effect of Resveratrol In Vitro and In Vivo.

Nanomaterials-based drug delivery systems display potent applications in cancer therapy. We synthesized a novel anticancer drug, nano-gold loaded with resveratrol (Res-GNPs), which were characterized using UV-Prove, zetasizer and transmission electron microscope. MTT assay, flow cytometry, TUNEL, immunohistochemistry and western blot analysis were performed to explore the antitumor activity of Res-GNPs in liver cancer cells and tumor xenografts. Res-GNPs showed a stronger effect on inhibiting cell proliferation and promoting apoptosis in Hepg2 cells than that of free Res. Res-GNPs induced apoptosis in Hepg2 cells by down-regulating pro-caspase-9, pro-caspase-3, PI3K and Akt and upregulating caspase-8 and bax. In xenograft studies, Res-GNPs remarkably suppressed tumor growth, promoted tumor apoptosis and decreased the expression of vascular endothelial growth factor (VEGF) in tumor tissue. Furthermore, HE staining showed that no observable toxicity was found in heart, liver, kidney and spleen. The datum confirmed that Res-GNPs possess better antitumor effect than Res in vitro and in vivo, which may be due to gold nanoparticles carry more resveratrol into cells and locate in mitochondria. These results suggested that Res-GNPs possess significantly better anti-cancer effect than Res alone in vitro and in vivo, which may be helpful for the clinical therapy of liver cancer.

Development and effects of tacrolimus-loaded nanoparticles on the inhibition of corneal allograft rejection

Tacrolimus has been widely applied to prevent organ rejection after transplantation. However, the conventional pharmaceutical formulation of tacrolimus limits its applications in ocular therapy due to its hydrophobicity and low corneal penetrability. We optimized tacrolimus-loaded methoxy poly (ethylene glycol-block-poly (d, l)-lactic-co-glycolic acid) nanoparticles (TAC-NPs) by simple and effective nanotechnology as a drug delivery system for corneal graft rejection to overcome these drawbacks. The prepared TAC-NPs were 82.9 ± 1.3 nm in size, and the drug loading and encapsulation efficiency were 8.01 ± 0.23% and 80.10 ± 2.33%. Furthermore, New Zealand rabbits were used to analyze the single-dose pharmacokinetics of the TAC-NPs using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). In rats with allogenic penetrating keratoplasty, the administration of TAC-NPs dispersion drops improved the TAC concentrations in the aqueous humor and cornea, consistent with a significantly higher effective inhibition of IL-2, IL-17, and VEGF expression compared with conventional 0.1% tacrolimus drops. Meanwhile, we also compared two different topical administration methods (including eye drop and subconjunctival injection) of TAC-NPs to maximize the sustained release characteristic of NPs. In summary, the small-sized TAC-NPs enhanced transcorneal permeation and absorption of TAC and more effectively inhibited corneal allograft rejection, which indicated that biodegradable polymeric nanomaterials-based drug delivery system had great potential for improving the clinical therapy efficacy of hydrophobic drugs.

Carbon-gold hybrid nanoprobes for real-time imaging, photothermal/photodynamic and nanozyme oxidative therapy.

Rationale: Recently, there is one-fifth of human deaths caused by cancer, leading to cancer treatment remains a hard nut to crack in the medical field. Therefore, as an emerging diagnostic technology, mesoporous nanomaterials-based drug delivery systems integrated diagnosis and therapy have aroused tremendous interest owing to visually targeting effect and superior therapy efficacy compared with traditional cancer treatment.Methods: In this work, we have successfully synthesized mesoporous carbon-gold hybrid nanozyme nanoprobes, whereby mesoporous carbon nanospheres were doped with small gold nanoparticles (OMCAPs) and further stabilized with a complex of reduced serum albumin and folic acid (rBSA-FA). After loading IR780 iodide, the OMCAPs@ rBSA-FA@IR780 nanoprobes were finally accomplished for real-time imaging, photothermal/photodynamic and nanozyme oxidative therapy.Results: Herein, acid oxidized MCAPs possessed large surface area and numerous -COOH groups, which could be used to surface chemically modify numerous targeting molecules and load abundant NIR dye IR780, as well as be acted as photothermal reagents to enhance photothermal therapy effect. In addition, the small Au NPs embedded in OMCAPs were utilized as nanozyme to catalyze H2O2 located in tumor cells to generate ·OH for intracellular oxidative damage of tumor. Besides, as a commonly used near-infrared (NIR) fluorescence dye, the loaded IR780 iodide could not only apply for real-time imaging, but also effectively enhance photo-thermal therapy (PTT) upon the 808 nm laser irradiation. Moreover, FA molecules could enhance the targeted efficiency of the nanoprobes to the gastric tumor site. According to the systematical study in vitro and in vivo, our fabricated nanoprobes based on carbon-gold hybrid (OMCAPs@ rBSA-FA@IR780) revealed excellent tumor targeting efficacy, long tumor retention and favorably therapeutic effect for tumor.Conclusion: All the results demonstrated that here synthesized probes exhibited excellently diagnostic and therapeutic performance, indicating our technology may potentially offer an outstanding strategy for tumor-targeting theranostics.

Mass spectrometry imaging of the in situ drug release from nanocarriers.

It is crucial but of a great challenge to study in vivo and in situ drug release of nanocarriers when developing a nanomaterial-based drug delivery platform. We developed a new label-free laser desorption/ionization mass spectrometry (MS) imaging strategy that enabled visualization and quantification of the in situ drug release in tissues by monitoring intrinsic MS signal intensity ratio of loaded drug over the nanocarriers. The proof of concept was demonstrated by investigating the doxorubicin (DOX)/polyethylene glycol-MoS2 nanosheets drug delivery system in tumor mouse models. The results revealed a tissue-dependent release behavior of DOX during circulation with the highest dissociation in tumor and lowest dissociation in liver tissues. The drug-loaded MoS2 nanocarriers are predominantly distributed in lung, spleen, and liver tissues, whereas the accumulation in the tumor was unexpectedly lower than in normal tissues. This new strategy could also be extended to other drug-carrier systems, such as carbon nanotubes and black phosphorus nanosheets, and opened a new path to evaluate the drug release of nanocarriers in the suborgan level.

Overcoming the Blood-Brain Barrier: The Role of Nanomaterials in Treating Neurological Diseases.

Therapies directed toward the central nervous system remain difficult to translate into improved clinical outcomes. This is largely due to the blood-brain barrier (BBB), arguably the most tightly regulated interface in the human body, which routinely excludes most therapeutics. Advances in the engineering of nanomaterials and their application in biomedicine (i.e., nanomedicine) are enabling new strategies that have the potential to help improve our understanding and treatment of neurological diseases. Herein, the various mechanisms by which therapeutics can be delivered to the brain are examined and key challenges facing translation of this research from benchtop to bedside are highlighted. Following a contextual overview of the BBB anatomy and physiology in both healthy and diseased states, relevant therapeutic strategies for bypassing and crossing the BBB are discussed. The focus here is especially on nanomaterial-based drug delivery systems and the potential of these to overcome the biological challenges imposed by the BBB. Finally, disease-targeting strategies and clearance mechanisms are explored. The objective is to provide the diverse range of researchers active in the field (e.g., material scientists, chemists, engineers, neuroscientists, and clinicians) with an easily accessible guide to the key opportunities and challenges currently facing the nanomaterial-mediated treatment of neurological diseases.

PEGylated mBPEI-rGO nanocomposites facilitate hepotocarcinoma treatment combining photothermal therapy and chemotherapy

Despite chemotherapy has been widely used for tumor therapy, the serious side effect is still a major challenge. Recently, two dimensional nanomaterial-based drug delivery systems have attracted wide concern due to their high drug loading and low side effect. In addition, some kinds of nanomaterials can directly act as a photosensitizer to induce cancer destruction. In this study, we developed a drug delivery system of mixture of high/low molecular weight branched polyethylenimine-polyethylene glycol-reduced graphene oxide (mBPEI-PEG-rGO) using reduced graphene oxide as matrix. A model drug of doxorubicin (DOX) was loaded on the nanocomposites with the efficiency of 81% and the release rate of more than 50% at acidic environment. In vitro experiments indicated that mBPEI-PEG-rGO-DOX with enhanced stability and biocompatibility efficiently delivered and released DOX into cells mainly through micropinocytosis and killed SMMC-7721 cells by inducing reactive oxygen species (ROS) and cell apoptosis. Furthermore, in vivo experiments indicated that the combination of intratumoral injection of mBPEI-PEG-rGO-DOX and local laser irradiation nearly ablated hepatocarcinoma. In conclusion, this new drug delivery system provided an alternative for combinational photothermal and chemotherapy against hepatocarcinoma.