Herein, a new Ugi multicomponent reaction strategy is described to enhance activity and solubility of the chemotherapeutic drug chlorambucil through its conjugation to poly(amidoamine) (PAMAM-NH2) dendrimers with the simultaneous introduction of lipi...
Exosomes are small vesicles with an average diameter of 100 nm that are produced by many, if not all, cell types. Exosome cargo includes lipids, proteins, and nucleic acids arranged specifically in the endosomes of donor cells. Exosomes can transfer...
The protein toxin C3bot from Clostridium botulinum is a mono-ADP-ribosyltransferase that selectively intoxicates monocyte-derived cells such as macrophages, osteoclasts, and dendritic cells (DCs) by cytosolic modification of Rho-A, -B, and -C. Here,...
Sesamol is effective against melanoma cells with less damage to normal cells. The underlying selective cytotoxicity of sesamol in melanoma vs. non-cancerous cells is undefined. Melanoma cells differ from normal cells by over-expression of the L-type...
Cells acquire polyamines putrescine (PUT), spermidine (SPD) and spermine (SPM) via the complementary actions of polyamine uptake and synthesis pathways. The endosomal P5B-type ATPases ATP13A2 and ATP13A3 emerge as major determinants of mammalian poly...
Background/Objectives: Endothelial peroxisome proliferator-activated receptor gamma (PPARγ) regulates adipose tissue by facilitating lipid uptake into white adipocytes, but the role of endothelial lipid transport in systemic energy balance rema...
Liposomes are bilayer membrane vesicles that can serve as vehicles for drug delivery. They are a good alternative to free drug administration that provides cell-targeted delivery into tumors, limiting the systemic toxicity of chemotherapeutic agents....
Photodynamic therapy (PDT) is an established treatment modality for a range of superficial and localized cancers. There has been tremendous interest in the development of advanced photosensitizers that exhibit superior photophysical properties, high...
A constantly elevated level of low-density lipoprotein cholesterol (LDL-C) is mainly associated with the development of atherosclerosis. The use of statins as a treatment for reducing plasma LDL-C levels has led, in some cases, to adverse side effect...
l-type amino acid transporter 1 (LAT1) is an amino acid transporter that is overexpressed in several types of cancer and, thus, it can be a potential target for chemotherapy. The objectives of this study were to (a) synthesize LAT1-targeted chlorambu...
It has been reported that [3-(1,1'-biphenyl-4-yl)-2-(1-methyl-5-dimethylamino-pentylamino)-3,4-dihydroquinazolin-4-yl]-N-benzylacetamide 2hydrochloride (KYS05090), a selective T-type Ca2+ channel blocker, reduces tumor volume and weight in the A549 x...
The prevalence of diabetes mellitus (DM), considered one of the most common metabolic disorders, has dramatically increased and resulted in higher rates of morbidity and mortality around the world in the past decade. It is well known that insulin res...
Both basic and preclinical research, as well as the development of new therapies, require tools that allow for the selective labelling of specific cell types and the targeted delivery of drugs. The developed tools must then be validated in biological...
Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than their parent, cyclodextrins. The cytotoxicity and cell uptake of ne...
Rociletinib (CO-1686), a 2,4-diaminopyrimidine derivative, is a highly potent tyrosine kinase inhibitor (TKI) that acts on epidermal growth factor receptor (EGFR) with L858R/T790M mutations. We supposed radioiodinated CO-1686 would function as a usef...
Despite advancements in treatment, the squamous cell carcinoma (OSCC) patient survival rate remains stagnant. Conventional therapies have limited effectiveness, necessitating novel agents. Our study aims to synthesize and characterize amorphous calci...
Biotin receptors are overexpressed by various types of solid cancer cells and play a significant role in tumor metabolism, growth, and metastasis. Thus, targeting the biotin receptors on tumor cells may enhance the efficiency and reduce the side-effe...
The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in the cell membrane disrupted by nsEP (20 or 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs)...
Telmisartan, an angiotensin II type 1 receptor (AT1R) antagonist, possesses cytotoxic activity towards BRAF-mutated melanoma cell lines. However, its antihypertensive effects limit its use in the population of normotensive patients. To mitigate this...
Sesamol is a compound reported to have anti-melanogenesis and anti-melanoma actions. Sesamol, however, has low intracellular drug concentration and fast excretion, which can limit its benefits in the clinic. To overcome this drawback and increase int...
Membrane type-1 matrix metalloproteinase (MT1-MMP or MMP-14) plays an important role in adverse cardiac remodelling. Here, we aimed to develop radiolabeled activatable cell penetrating peptides (ACPP) sensitive to MT1-MMP for the detection of elevate...
Genistein (GEN) is a soy-derived isoflavone that exhibits several biological effects, such as neuroprotective activity and the prevention of several types of cancer and cardiovascular disease. However, due to its poor water solubility and the extensi...
The ability to predict the behaviour of polymeric nanomedicines can often be obfuscated by subtle modifications to the corona structure, such as incorporation of fluorophores or other entities. However, these interactions provide an intriguing insigh...
The widespread use of synthetic aminopolycarboxylates, such as ethylenediaminetetraacetate (EDTA), as chelating agents has led to their contamination in the environment as stable metal–chelate complexes. Microorganisms can transport free EDTA,...
Decoration of nanoparticles with specific molecules such as antibodies, peptides, and proteins that preserve their biological properties is essential for the recognition and internalization of their specific target cells. Inefficient preparation of s...
Malignant hyperthermia (MH) is a genetic disorder triggered by depolarizing muscle relaxants or halogenated inhalational anesthetics in genetically predisposed individuals who have a chronic elevated intracellular Ca2+ concentration ([Ca2+]i) in thei...
Flavonoids have been reported to exert antihyperglycemic effects and have potential to enhance the current therapy options against type 2 diabetes mellitus. However, the structure activity relationships (SAR) studies of flavonoids against this diseas...
Cancer ablation therapies aim to be efficient while minimizing damage to healthy tissues. Nanosecond pulsed electric field (nsPEF) is a promising ablation modality because of its selectivity against certain cell types and reduced neuromuscular effect...
Due to their interesting size-dependent magnetic characteristics and relative biocompatibility, magnetic superparamagnetic iron oxide (SPIO) nanoparticles have been widely exploited as probes for cell and subcellular structure identification, as well...
Modulating signaling pathways for research and therapy requires either suppression or expression of selected genes or internalization of proteins such as enzymes, antibodies, nucleotide binding proteins or substrates including nucleoside phosphates a...
Near-infrared photoimmunotherapy (NIR-PIT) is a new phototherapy that utilizes a monoclonal antibody (mAb) against cancer antigens and a phthalocyanine dye, IRDye700DX (IR700) conjugate (mAb-IR700). Photodynamic therapy (PDT) is a combination therapy...
The PI3K/Akt/mTOR pathway has been well known to interact with the estrogen receptor (ER)-pathway and to be also frequently upregulated in aromatase inhibitor (AI)-resistant breast cancer patients. Intracellular levels of free amino acids, especially...
Boron neutron capture therapy (BNCT) requires pharmaceutical innovations and molecular-based evidence of effectiveness to become a standard cancer therapeutic in the future. Recently, in Japan, 4-borono-L-phenylalanine (BPA) was approved as a boron a...
Organic anion transporting polypeptide 1B1 (OATP1B1) is selectively expressed at the basolateral membrane of human hepatocytes and plays a crucial role in the absorption of various xenobiotic compounds, including many important clinical drugs. Oligom...
Molecular characterization is currently a key step in NSCLC therapy selection. Circulating tumor cells (CTC) are excellent candidates for downstream analysis, but technology is still lagging behind. In this work, we show that the mutational status of...
Oncolytic adenoviruses (OAd) can be employed to efficiently eliminate cancer cells through multiple mechanisms of action including cell lysis and immune activation. Our OAds, AdΔΔ and Ad-3∆-A20T, selectively infect, replicate in, an...
Background: Metastatic prostate cancer (mPrC), with a median survival of under 2 years, represents an important unmet medical need which may benefit from the development of more effective targeted drug delivery systems. Several cell surface receptors...
Calyculin A (Caly A) is cell permeable toxin widely used in cell biology research as an inhibitor of type 1 and type 2A protein Ser/Thr phosphatases of the PPP family. Here we tested effects of low concentrations of Caly A on proliferation of human c...
Cell membranes with their selective permeability play important functions in the tight control of molecular exchanges between the cytosol and the extracellular environment as the intracellular membranes do within the internal compartments. For this r...
Chemical and biochemical functionalization of nanoparticles (NPs) can lead to an active cellular uptake enhancing their efficacy thanks to the targeted localization in tumors. In the present study calcium carbonate nano-crystals (CCNs), stabilized by...
Theaflavins, the characteristic and bioactive polyphenols in black tea, possess the potential improving effects on insulin resistance-associated metabolic abnormalities, including obesity and type 2 diabetes mellitus. However, the related molecular m...
Research on platinum-based anticancer drugs continuously strives to develop new non-classical platinum complexes. Pt(IV) prodrugs are the most promising, and their activation-by-reduction mechanism of action is being explored as a prospect for higher...
Directed enzyme prodrug therapy (DEPT) strategies show promise in mitigating chemotherapy side effects during cancer treatment. Among these, the use of immobilized enzymes on solid matrices as prodrug activating agents (IDEPT) presents a compelling d...
l-Type amino acid transporter 1 (LAT1), expressed abundantly in the brain and placenta and overexpressed in several cancer cell types, has gained a lot of interest in drug research and development, as it can be utilized for brain-targeted drug delive...
Cell-penetrating peptides (CPPs) comprise a class of short polypeptides that possess the ability to selectively interact with the cytoplasmic membrane of certain cell types, translocate across plasma membranes and accumulate in the cell cytoplasm, or...
The alkylpyridinium polymer APS8, a potent antagonist of α7 nicotinic acetylcholine receptors (nAChRs), selectively induces apoptosis in non-small cell lung cancer cells but not in normal lung fibroblasts. To explore the potential therapeutic v...
The influence of DNA vaccine formulations on immune responses in combination with adjuvants was investigated with the aim to increase cell-mediated immunity against plasmid DNA (pDNA) encoding Mycobacterium tuberculosis antigen 85A. Different ratios...
Upconverting nanoparticles (UCNPs) are of particular interest in nanomedicine for in vivo deep-tissue optical cancer bioimaging due to their efficient cellular uptake dependent on polymer coating. In this study, particles, ca. 25 nm in diameter, were...
In this study, we examined the effect of cationic lipid type in folate (FA)-polyethylene glycol (PEG)-modified cationic liposomes on gene-silencing effects in tumor cells using cationic liposomes/siRNA complexes (siRNA lipoplexes). We used three type...
Overcoming the limitations for efficient and selective drug delivery is one of the most challenging obstacles for newly designed anticancer agents. In this study, we present two types of platinum-based nanoparticles (NP), ultrasmall 2 nm PtNPs and co...
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