Drug Vehicle Research Articles

Inducing Mitotic Catastrophe as a Therapeutic Approach to Improve Outcomes in Ewing Sarcoma.

Ewing sarcoma (EWS) is an aggressive pediatric malignancy of the bone and soft tissues in need of novel therapeutic options. To identify potential therapeutic targets, we focused on essential biological pathways that are upregulated by EWS-FLI1, the primary oncogenic driver of EWS, including mitotic proteins such as Aurora kinase A (AURKA) and kinesin family member 15 (KIF15) and its binding partner, targeting protein for Xklp2 (TPX2). KIF15/TPX2 cooperates with KIF11, a key mitotic kinesin essential for mitotic spindle orientation. Given the lack of clinical-grade KIF15/TPX2 inhibitors, we chose to target KIF11 (using SB-743921) in combination with AURKA (using VIC-1911) given that phosphorylation of KIF15S1169 by Aurora A is required for its targeting to the spindle. In vitro, the drug combination demonstrated strong synergy (Bliss score ≥ 10) at nanomolar doses. Colony formation assay revealed significant reduction in plating efficiency (1-3%) and increased percentage accumulation of cells in the G2/M phase with the combination treatment (45-52%) upon cell cycle analysis, indicating mitotic arrest. In vivo studies in EWS xenograft mouse models showed significant tumor reduction and overall effectiveness: drug combination vs. vehicle control (p ≤ 0.01), SB-743921 (p ≤ 0.01) and VIC-1911 (p ≤ 0.05). Kaplan-Meier curves demonstrated superior overall survival with the combination compared to vehicle or monotherapy arms (p ≤ 0.0001).

Advances in anti-tumor based on various anaerobic bacteria and their derivatives as drug vehicles.

Cancer therapies, such as chemotherapy and radiotherapy, are often unsatisfactory due to several limitations, including drug resistance, inability to cross biological barriers, and toxic side effects on the body. These drawbacks underscore the need for alternative treatments that can overcome these challenges and provide more effective and safer options for cancer patients. In recent years, the use of live bacteria, engineered bacteria, or bacterial derivatives to deliver antitumor drugs to specific tumor sites for controlled release has emerged as a promising therapeutic tool. This approach offers several advantages over traditional cancer therapies, including targeted drug delivery and reduced toxicity to healthy tissues. Ongoing research in this field holds great potential for further developing more efficient and personalized cancer therapies, such as E. coli, Salmonella, Listeria, and bacterial derivatives like outer membrane vesicles (OMVs), which can serve as vehicles for drugs, therapeutic proteins, or antigens. In this review, we describe the advances, challenges, and future directions of research on using live bacteria or OMVs as carriers or components derived from bacteria of delivery systems for cancer therapy.

A Convergent fabrication of silk fibroin nanoparticles on quercetin loaded metal-organic frameworks for promising nanocarrier of myocardial infraction

The biomacromolecule silk fibroin (SF) may be constructed to promote biomimetic nucleation and nanostructures of inorganic nanomaterials, offering it a promising candidate for use in various biomimetic applications. We combined SF-NPs and ZIF-8-NPs to fabricate new drug vehicles that effectively release the drug. SF nanoparticles (SF-NPs) were assembled into quercetin (QCT), a myocardial drug added to fabricate QSF-NPs. By acting as a template for the ZIF-8 nucleation onto the surface, the QSF-NPs fabricated core-shell-structured nanocomposites (named QSF@Z-NCs) with ZIF-8 as the core-shell and the QSF-NPs. The biocompatibility analysis using the MTT assay revealed that the developed QCT, SF-NPs, and QSF@Z-NCs are not harmful to cardiac myoblast (H9C2) cells. The in vivo model demonstrated that H9C2 cells encouraged cardiomyocyte fibre regeneration in myocardial infarction rats. We fabricated a brand-new technique using H9C2 cells and QSF@Z-NCs that might encourage the healing processes in myocardial ischemia cells. This study's results demonstrate that it successfully treats myocardial injury.

Controlled delivery of sildenafil by β-Cyclodextrin-decorated sulfur-doped carbon nanodots: a synergistic activation of ROS signaling in tumors overexpressing PDE-5

Fluorescent sulfur- and nitrogen-doped carbon nanodots (CDs) are zero-dimensional nanoparticles that mediate ROS production in cancer cells, displaying inherent anticancer properties. Thus, they have been proposed as nanotheranostic tools useful in image-guided cancer therapy. Here, we try to show that cancerous cells (high PDE-5 expression) receiving sildenafil delivered by CDs-based nanostructures promote positive reinforcement of PDE-5-mediated cell death via the overexpression of genes involved in the production of ROS.We explored the regioselective Huisgen cycloaddition between azide-β-cyclodextrin and CDs-alkyne to synthetize homogeneous nanostructures, named CDs-PEG4-β-Cdx, consisting of CDs functionalized at the surface with β-cyclodextrins capable of including high amount drugs such as sildenafil (>20 % w/w), and releasing them in a controlled manner. We investigated how CDs-PEG4-β-Cdx bearing sildenafil enter cells, enhancing ROS production and cell death specifically in cancer cells overexpressing PDE-5. These nanoplatforms go beyond the bounds of EPR-based nanomedicines in which carriers are conceived as inert vehicles of toxic drugs. Our findings enable the development of clever anticancer nanoplatforms that synergistically combine nanomedicines that perturb the mitochondrial electron transport chain (ROS production) with PDE-5 inhibitors which trigger oxidative stress specifically in cancer cells regardless of their location.

DNA Origami: From Molecular Folding Art to Drug Delivery Technology.

DNA molecules that store genetic information in living creatures can be repurposed as building blocks to construct artificial architectures, ranging from the nanoscale to the microscale. The precise fabrication of self-assembled DNA nanomaterials and their various applications have greatly impacted nanoscience and nanotechnology. More specifically, the DNA origami technique has realized the assembly of various nanostructures featuring rationally predesigned geometries, precise addressability, and versatile programmability, as well as remarkable biocompatibility. These features have elevated DNA origami from academic interest to an emerging class of drug delivery platform for a wide range of diseases. In this minireview, the latest advances in the burgeoning field of DNA-origami-based innovative platforms for regulating biological functions and delivering versatile drugs are presented. Challenges regarding the novel drug vehicle's safety, stability, targeting strategy, and future clinical translation are also discussed.

VAR2CSA protein for malaria vaccine or anticancer drug delivery? A review of preclinical and clinical research

Variant surface antigen 2- chondroitin sulfate A (VAR2CSA) is a protein belonging to the Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family. Since the discovery of the protein, various studies have been carried out to utilize VAR2CSA in the clinical field. The typical application is the development of malaria vaccines and anticancer drug carriers based on VAR2CSA. Will anticancer drugs (with VAR2CSA vehicle) work effectively in patients who have already received the VAR2CSA-based malaria vaccine? Given that theoretically, the presence of antibodies triggered by the VAR2CSA vaccine might be against anticancer drugs delivered by VAR2CSA. Therefore, a review regarding the development of research on VAR2CSA, especially as a vaccine or anticancer drug vehicle, is needed. This paper provides an overview of current knowledge about VAR2CSA including its structure and function, biochemical aspects, research approaches both in vitro, ex vivo and in vivo, and the development of potential studies of VAR2CSA in the field of medicine. The literature search was carried out systematically from the PubMed database with the keywords “VAR2CSA”, “VAR2CSA” AND “vaccine”, "VAR2CSA" AND "drug delivery", "VAR2CSA" AND "cancer", "VAR2CSA" AND "placental malaria", "VAR2CSA" AND "review". A Study of VAR2CSA shows promising results, especially in the development of VAR2CSA as the main candidate for the placental malaria vaccine and anticancer drug carrier. Current findings reveal that both studies will carry out clinical trials soon. However, limitations of the study should be considered in future clinical applications for more effective cancer treatment, such as the administration of anticancer drugs by VAR2CSA vehicles on patients who have already received VAR2CSA-based antimalarial vaccines. Furthermore, an example of promising future research is leveraging other domains of VAR2CSA that have not been explored yet.

Cerium doped dendritic mesoporous bioactive glass nanoparticles with bioactivity and drug delivery capability

Dendritic mesoporous bioactive glass nanoparticles (DMBGNs) with unique three-dimensional structures are attracting increasing attention for biomedical applications. However, it is still challenging to tune the chemical composition of DMBGNs. In this work, we provide for the first time a feasible post-impregnation approach to incorporate metallic ions (Ca and Ce) into dendritic mesoporous silica nanoparticles, resulting in SiO2-CaO and SiO2-CaO-CeO2 (Ce-DMBGNs) without destroying the dendritic mesoporous topography. Both DMBGNs and Ce-DMBGNs were amorphous, negatively charged, with a hydrodynamic size of ∼200 nm. The synthesized DMBGNs and Ce-DMBGNs exhibited high bioactivity as evidenced by the rapid formation of hydroxyapatite (HA) after immersion in simulated body fluid (SBF) for 7 days. In addition, DMBGNs and Ce-DMBGNs showed high propolis loading efficiency and sustained release behavior. The results suggest that the developed Ce-DMBGNs have the potential to be used as a delivery vehicle of therapeutic ions and drugs in bone regeneration applications.

Nanoparticle platform comprising lipid-tailed pH-sensitive carbon dots with minimal drug loss

Herein, we synthesized a lipid-mimicking organic material (PCD_FA) that can surpass the efficacy of lipid-based nanoparticles and demonstrated its potential as a delivery vehicle for various hydrophilic drugs. PCD_FA is a conjugate of pH-sensitive carbon dots (PCDs) and fatty acids (FAs) and has potential applications in several fields owing to various combinations of carbon dots (CDs) and FAs. Similar to phospholipids, PCD-FAs have hydrophilic heads and hydrophobic tails that allow them to self-form nanoparticles (Coposomes) in the aqueous phase. Coposomes can easily combine various hydrophilic head and hydrophobic tail combinations, and several drugs can be encapsulated, or drug release patterns can be controlled according to each property. We analyzed the differences in size, drug loading efficiency, and drug release patterns of Coposomes depending on the type of FAs and characteristics of the encapsulated drugs. Additionally, cell entry and intracellular drug release mechanisms of the Coposomes were identified. The applicability of Coposomes as drug delivery carriers for tumor treatment has been demonstrated in comparison with that of liposomes formulation in tumor-bearing mouse models. Consequently, this study presents possibilities for the synthesis and application of various amphiphilic lipid-mimicking organic materials via the combination of CDs and FAs with various functions.

Augmentation of anti-proliferative efficacy of quercetin encapsulated chitosan nanoparticles by induction of cell death via mitochondrial membrane permeabilization in oral cancer

Quercetin (QCT), an antioxidant plant flavonoid, is known to impart prominent anti-cancer properties. However, its clinical application as a potential drug is hindered owing to its hydrophobicity, extensive metabolism, low absorption, and rapid elimination. The drawbacks of these phytochemical-based therapies can be addressed using nanotechnology-based drug delivery systems. In this study, we sought to develop chitosan nanoparticles (CSNPs) as the drug vehicle for encasing quercetin (QCT-CSNPs) and further investigate its anti-tumor potential against human oral cancer cell line Cal33. Our findings indicate that the average particle diameter of the formulated chitosan nanoparticles was around 100 nm, and they had a spherical structure, as per the TEM and FESEM images. The efficient entrapment of quercetin inside the CSNPs matrix is confirmed by XRD, UV–Vis spectrophotometry, FTIR, and DSC analysis. The in vitro cell cytotoxicity study against Cal33 oral cancer cells revealed that QCT-CSNPs exhibited superior toxicity compared to free QCT post-24-hour treatment. The improved anti-cancer efficacy of QCT-CSNPs was further confirmed by enhanced cellular apoptosis, colony formation inhibition, migration inhibition, and chromatin condensation. Moreover, the mitochondrial dysfunction and enhanced ROS (Reactive oxygen species) production indicated mitochondrial-mediated cell death in QCT-CSNPs treated Cal33 cells. In conclusion, our data suggest that quercetin-encapsulated chitosan nanoparticles may serve as a potential drug candidate against oral cancer.

Dual functionalized hyaluronic acid micelles loading paclitaxel for the therapy of breast cancer.

Although many carriers for the delivery of chemotherapeutic drugs have been investigated, the disadvantages of passive targeting and uncontrolled drug release limit their utility. Herein, hyaluronic acid (HA) was hydrophobically modified to serve as a carrier for binding to cluster determinant 44 (CD44) overexpressed on tumor cell surfaces. Specifically, after deacetylation, HA was grafted to dodecylamine or tetradecylamine to afford amphiphilic zwitterionic polymer micelles, designated dHAD and dHAT, respectively, for the delivery of paclitaxel (PTX). The micelles were negatively charged at pH 7.4 and positively charged at pH 5.6, and this pH sensitivity facilitated PTX release under acidic conditions. The cell uptake efficiencies of the dHAD-PTX and dHAT-PTX micelles by MCF-7 cells after 4h of incubation were 96.9% and 95.4%, respectively, and their affinities for CD44 were twice that of HA. Furthermore, the micelles markedly inhibited tumor growth both in vitro and in vivo, with IC50 values of 1.943μg/mL for dHAD-PTX and 1.874μg/mL for dHAT-PTX for MCF-7 cells; the tumor inhibition rate of dHAD-PTX (92.96%) was higher than that of dHAT-PTX (78.65%). Importantly, dHAD and dHAT micelles showed negligible systemic toxicity. Our findings suggest that these micelles are promising delivery vehicles for antitumor drugs.

Cancer phototherapy with nano-bacteria biohybrids.

The utilization of light for therapeutic interventions, also known as phototherapy, has been extensively employed in the treatment of a wide range of illnesses, including cancer. Despite the benefits of its non-invasive nature, phototherapy still faces challenges pertaining to the delivery of phototherapeutic agents, phototoxicity, and light delivery. The incorporation of nanomaterials and bacteria in phototherapy has emerged as a promising approach that leverages the unique properties of each component. The resulting nano-bacteria biohybrids exhibit enhanced therapeutic efficacy when compared to either component individually. In this review, we summarize and discuss the various strategies for assembling nano-bacteria biohybrids and their applications in phototherapy. We provide a comprehensive overview of the properties and functionalities of nanomaterials and cells in the biohybrids. Notably, we highlight the roles of bacteria beyond their function as drug vehicles, particularly their capacity to produce bioactive molecules. Despite being in its early stage, the integration of photoelectric nanomaterials and genetically engineered bacteria holds promise as an effective biosystem for antitumor phototherapy. The utilization of nano-bacteria biohybrids in phototherapy is a promising avenue for future investigation, with the potential to enhance treatment outcomes for cancer patients.

Designed ultrafine polymer-coated manganese-cobalt ferrite nanoparticles loaded with anticancer drug: efficacy enhancement through host:guest complexation on the polymer surface

Magnetic nanomaterials of different compositions have been examined, focusing on the magnetic field-directed transport of drugs. The size, shape, surface modification and composition variations make every magnetic nanostructure a unique nanocarrier. In this work, we carry out a hydrothermal synthesis of novel manganese-cobalt co-incorporated magnetic ferrite nanoparticles. The particles are characterized using x-ray diffraction, transmission electron microscopy, thermogravimetry and x-ray photoelectron spectroscopy. The size of the nanoparticles is below 10 nm, and they are found to fall under the face-centered cubic system. The nanoparticles are coated with the β-cyclodextrin and folate co-tethered polyethylene glycol. Vibrating sample magnetometry reveals the soft ferromagnetic nature of the nanoparticles with a saturation magnetization value of 28.11 emu g−1 for the coated nanoparticles. The polymer on the nanoparticles allows the loading of the drug feasible, and the encapsulation efficiency is ∼93%. The in vitro release of the drug is monitored and it is observed that the release occurs over 130 h. The cytotoxicity of the free- and camptothecin-loaded manganese-ferrite nanocarrier on breast cancer cell lines is investigated. The IC50 value of the drug-loaded nanocarrier is 2.22 µg mL−1 which is significantly lower than that of the free drug. The drug-encapsulated nanocarrier releases the cargo slowly and continuously and shows increased efficacy, which represents the significance of the nanocarrier. The results present the designed nanomaterial as a suitable anticancer drug vehicle.

Calcium carbonate nanoparticles tumor delivery for combined chemo-photodynamic therapy: Comparison of local and systemic administration.

The use of nanoparticles (NPs) as delivery vehicles for multiple drugs is an intensively developing area. However, the success of NPs' accumulation in the tumor area for efficient tumor treatment has been recently questioned. Distribution of NPs in a laboratory animal is mainly related to the administration route of NPs and their physicochemical parameters, which significantly affect the delivery efficiency. In this work, we aim to compare the therapeutic efficiency and side effects of the delivery of multiple therapeutic agents with NPs by both intravenous and intratumoral injections. For this, we systematically developed universal nanosized carriers based on calcium carbonate (CaCO3) NPs (< 100nm) that were co-loaded with a photosensitizer (Chlorin e6, Ce6) and chemotherapeutic agent (doxorubicin, Dox) for combined chemo- and photodynamic therapy (PDT) of B16-F10 melanoma tumors. By performing intratumoral or intravenous injections of NPs, we observed different biodistribution profiles and tumor accumulation efficiencies. In particular, after intratumoral administration of NPs, they mostly remained in the tumors (> 97%); while for intravenous injection, the tumor accumulation of NPs was determined to be 8.67-12.4 ID/g%. Although the delivery efficiency of NPs (presented in ID/g%) in the tumor differs, we have developed an effective strategy for tumor inhibition based on combined chemo- and PDT by both intratumoral and intravenous injections of NPs. Notably, after the combined chemo- and PDT treatment with Ce6/Dox@CaCO3 NPs, all B16-F10 melanoma tumors in mice shrank substantially, by approximately 94% for intratumoral injection and 71% for intravenous injection, which are higher values compared to mono-therapy. In addition, the CaCO3 NPs showed negligible in vivo toxicity towards major organs such as the heart, lungs, liver, kidneys, and spleen. Thus, this work demonstrates a successful approach for the enhancement of NPs' efficiency in combined anti-tumor therapy.

Micellization of phenothiazine drug and nonionic surfactant TX-165 mixture in different composition and media: surface tension and UV-visible study

ABSTRACT Micelles serve as a replica for the investigation of bio-membranes as physicochemical association of drugs with micelles is envisioned as their interconnection with bio-membranes. Micellization properties of promethazine hydrochloride (PMT) with TX-165 (a nonionic surfactant) in aqueous, 50 mmolkg−1 NaCl and 500 mmolkg−1 urea solutions were analysed in detail using surface tension measuring tool. PMT is employed as an analgesic, anticholinergic, sedative, antihistaminic as well as antipsychotic drug. UV-visible spectroscopy is also utilised to evaluate PMT-TX-165 interactions in an aqueous solution. Pure constituent and their mixtures (PMT + TX-165) of each composition showed lower cmc value in NaCl than in the aqueous system, while urea-containing solutions showed higher cmc value. Increasing the mole fraction (α 1) of TX-165 in mixed systems increases the interaction between the employed constituents (PMT and TX-165). The evaluated Gibbs free energy values of singular, and mixed system in each media were attained negative that uncovering that each system depicted the spontaneity of micellization. Various thermodynamic parameters were examined and discussed thoroughly. A UV-visible measurement also confirms that the components interact in treaty with surface tension measurements. Based on the results of this study, TX-165 was designed in a forthright manner, which could be an efficient drug delivery vehicle for phenothiazine drugs.

Production of an interleukin-10 blocking antibody by genetically engineered macrophages increases cancer cell death in human gastrointestinal tumor slice cultures.

Although it can promote effector T-cell function, the summative effect of interleukin-10 (IL-10) in the tumor microenvironment (TME) appears to be suppressive; therefore, blocking this critical regulatory cytokine has therapeutic potential to enhance antitumor immune function. As macrophages efficiently localize to the TME, we hypothesized that they could be used as a delivery vehicle for drugs designed to block this pathway. To test our hypothesis, we created and evaluated genetically engineered macrophages (GEMs) that produce an IL-10-blocking antibody (αIL-10). Healthy donor human peripheral blood mononuclear cells were differentiated and transduced with a novel lentivirus (LV) encoding BT-063, a humanized αIL-10 antibody. The efficacy of αIL-10 GEMs was assessed in human gastrointestinal tumor slice culture models developed from resected specimens of pancreatic ductal adenocarcinoma primary tumors and colorectal cancer liver metastases. LV transduction led to sustained production of BT-063 by αIL-10 GEMs for at least 21 days. Transduction did not alter GEM phenotype as evaluated by flow cytometry, but αIL-10 GEMs produced measurable quantities of BT-063 in the TME that was associated with an ~5-fold higher rate of tumor cell apoptosis than control.

Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles

Cell-derived small extracellular vesicles have been exploited as potent drug vehicles. However, significant challenges hamper their clinical translation, including inefficient cytosolic delivery, poor target-specificity, low yield, and inconsistency in production. Here, we report a bioinspired material, engineered fusogen and targeting moiety co-functionalized cell-derived nanovesicle (CNV) called eFT-CNV, as a drug vehicle. We show that universal eFT-CNVs can be produced by extrusion of genetically modified donor cells with high yield and consistency. We demonstrate that bioinspired eFT-CNVs can efficiently and selectively bind to targets and trigger membrane fusion, fulfilling endo-lysosomal escape and cytosolic drug delivery. We find that, compared to counterparts, eFT-CNVs significantly improve the treatment efficacy of drugs acting on cytosolic targets. We believe that our bioinspired eFT-CNVs will be promising and powerful tools for nanomedicine and precision medicine.

The feasibility of oral targeted drug delivery: Gut immune to particulates?

Targeted drug delivery is constantly updated with a better understanding of the physiological and pathological features of various diseases. Depending on high safety, good compliance and many other undeniable advantages, attempts have been undertaken to complete an intravenous-to-oral conversion of targeted drug delivery. However, oral delivery of particulates to systemic circulation is highly challenging due to the biochemical aggressivity and immune exclusion in the gut that restrain absorption and access to the bloodstream. Little is known about the feasibility of targeted drug delivery via oral administration (oral targeting) to a remote site beyond the gastrointestinal tract. To this end, this review proactively contributes to a special dissection on the feasibility of oral targeting. We discussed the theoretical basis of oral targeting, the biological barriers of absorption, the in vivo fate and transport mechanisms of drug vehicles, and the effect of structural evolution of vehicles on oral targeting as well. At last, a feasibility analysis on oral targeting was performed based on the integration of currently available information. The innate defense of intestinal epithelium does not allow influx of more particulates into the peripheral blood through enterocytes. Therefore, limited evidence and lacking exact quantification of systemically exposed particles fail to support much success with oral targeting. Nevertheless, the lymphatic pathway may serve as a potentially alternative portal of peroral particles into the remote target sites via M-cell uptake. Targeting a remote nidus beyond the gut via oral administration is highly challenged by various biological barriers over and above the prevailing strategies.

Polysaccharides polymers for glaucoma treatment-a review.

One of the major challenges in preventing glaucoma progression is patient compliance with medication regimens. Since conventional ophthalmic dosage forms have numerous limitations, researchers have been intensively working on developing polymers-based delivery systems for glaucoma drugs. Specifically, research and development efforts have increased using polysaccharide polymers such as sodium alginate, cellulose, β-cyclodextrin, hyaluronic acid, chitosan, pectin, gellan gum, galactomannans for sustained release to the eye to overcome treatment challenges, showing promise in improving drug release and delivery, patient experience, and treatment compliance. In the recent past, multiple research groups have successfully designed sustained drug delivery systems, promoting the efficacy as well as the feasibility of glaucoma drugs with single/combinations of polysaccharides to eliminate the drawbacks associated with the glaucoma treatment. Naturally available polysaccharides, when used as drug vehicles can increase the retention time of eye drops on the ocular surface, leading to improved drug absorption and bioavailability. Additionally, some polysaccharides can form gels or matrices that can release drugs slowly over time, providing sustained drug delivery and reducing the need for frequent dosing. Thus, this review aims to provide an overview of the pre-clinical and clinical studies of polysaccharide polymers applied for glaucoma treatment along with their therapeutic outcomes.

Long-circulating gambogic acid-loaded nanodiamond composite nanosystem with inhibition of cell migration for tumor therapy

Herein, ultra dispersed and stably suspended nanodiamonds (NDs) were demonstrated to have a high load capacity, sustained release, and ability to serve as a biocompatible vehicle for delivery anticancer drugs. NDs with size of 50–100 nm exhibited good biocompatibility in normal human liver (L-02) cells. In particular, 50 nm ND not only promoted the noticeable proliferation of the L-02 cells but also can effectively inhibited the migration of human liver carcinoma (HepG2) cells. The gambogic acid-loaded nanodiamond (ND/GA) complex assembled by π–π stacking exhibits ultrasensitive and apparent suppression efficiency on the proliferation of HepG2 cells through high internalization and less efflux compared to free GA. More importantly, the ND/GA system can significantly increase the intracellular reactive oxygen species (ROS) levels in HepG2 cells and thus induce the cell apoptosis. The increase in intracellular ROS levels causes damage to the mitochondrial membrane potential (MMP) and activates cysteinyl aspartate specific proteinase 3 (Caspase-3) and cysteinyl aspartate specific proteinase 9 (Caspase-9), which leads to the occurrence of apoptosis. In vivo experiments also confirmed that the ND/GA complex has a much higher anti-tumor capability than free GA. Thus, the current ND/GA system is promising for cancer therapy.

Two-dimensional silicon carbide monolayer as a promising drug delivery vehicle for hydroxyurea anti-cancer drug

Two-dimensional silicon carbide monolayer as a promising drug delivery vehicle for hydroxyurea anti-cancer drug