Impact of cationic surfactant-induced DNA compaction on the characteristics of a minor groove bound flavonol

3-Hydroxyflavone (3-HF), which binds to the minor groove of DNA, is a strong antioxidant and hence a potent therapeutic and diagnostic agent. A special photo-property, called excited state intramolecular proton...

SapC–DOPS as a Novel Therapeutic and Diagnostic Agent for Glioblastoma Therapy and Detection: Alternative to Old Drugs and Agents

Glioblastoma multiforme (GBM), the most common type of brain cancer, is extremely aggressive and has a dreadful prognosis. GBM comprises 60% of adult brain tumors and the 5 year survival rate of GBM patients is only 4.3%. Standard-of-care treatment includes maximal surgical removal of the tumor in combination with radiation and temozolomide (TMZ) chemotherapy. TMZ is the “gold-standard” chemotherapy for patients suffering from GBM. However, the median survival is only about 12 to 18 months with this protocol. Consequently, there is a critical need to develop new therapeutic options for treatment of GBM. Nanomaterials have unique properties as multifunctional platforms for brain tumor therapy and diagnosis. As one of the nanomaterials, lipid-based nanocarriers are capable of delivering chemotherapeutics and imaging agents to tumor sites by enhancing the permeability of the compound through the blood–brain barrier, which makes them ideal for GBM therapy and imaging. Nanocarriers also can be used for delivery of radiosensitizers to the tumor to enhance the efficacy of the radiation therapy. Previously, high-atomic-number element-containing particles such as gold nanoparticles and liposomes have been used as radiosensitizers. SapC–DOPS, a protein-based liposomal drug comprising the lipid, dioleoylphosphatidylserine (DOPS), and the protein, saposin C (SapC), has been shown to be effective for treatment of a variety of cancers in small animals, including GBM. SapC–DOPS also has the unique ability to be used as a carrier for delivery of radiotheranostic agents for nuclear imaging and radiotherapeutic purposes. These unique properties make tumor-targeting proteo-liposome nanocarriers novel therapeutic and diagnostic alternatives to traditional chemotherapeutics and imaging agents. This article reviews various treatment modalities including nanolipid-based delivery and therapeutic systems used in preclinical and clinical trial settings for GBM treatment and detection.

Melanocortin receptors in GtoPdb v.2021.3

Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP-MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development.

An assessment of in-vitro and in-vivo evaluation methods for theranostic nanomaterials

: Nanoparticles (NPs) as nanocarriers have emerged as novel and promising theranostic agents. The term theranostics revealed the properties of NPs capable of diagnosing the disease at an early stage and/or treating the disease. Such NPs are usually developed employing a surface engineering approach. The theranostic agents comprise NPs loaded with a drug/diagnostic agent that delivers it precisely to the target site. Theranostics is a field with promising results in enhancing therapeutic efficacy facilitated through higher payload at the targeted tissue, reduced dose, and dose-dependent side effects. However, controversies in terms of toxicity and size-dependent properties have often surfaced for NPs. Thus, a stringent in-vitro and in-vivo evaluation is required to develop safe and non-toxic NPs as theranostic agents. The review also focuses on the various entry points of NPs in the human system and their outcomes, including toxicity. It elaborates the evaluation criteria to ensure the safe use of NPs for diagnostic and therapeutic purposes.

Targeted SPION siderophore conjugate loaded with doxorubicin as a theranostic agent for imaging and treatment of colon carcinoma

Recently, the siderophores have opened new horizons in nanomedicine. The current study aimed to design a theranostic platform based on superparamagnetic iron oxide nanoparticles-pyoverdine (SPION/PVD) conjugates bound to MUC1 aptamer (MUC1Apt) and loaded with doxorubicin (DOX) as an anti-cancer agent. The SPION/PVD complex was covalently conjugated to MUC1Apt and loaded with DOX to prepare a targeted drug delivery system (SPION/PVD/MUC1Apt/DOX). The investigation of cellular cytotoxicity and uptake of formulations by MTT and flow cytometry in both MUC1 positive (C26) and MUC1 negative (CHO) cell lines revealed that MUC1Apt could improve both cellular uptake and toxicity in the C26 cell line. The evaluation of tumor-targeting activity by in vivo bio-distribution showed that the targeted formulation could enhance tumor inhibitory growth effect and survival rate in C26 tumor-bearing mice. Furthermore, the potential of synthesized SPION/PVD/MUC1Apt/DOX complex as diagnostic agents was investigated by magnetic resonance imaging (MRI) which improved the contrast of tumor site in MRI. Our findings confirm that aptamer-targeted PVD chelated the SPION as a diagnostic agent and loaded with DOX as a chemotherapeutic drug, would be beneficial as a novel theranostic platform.

Potential of Cyanine Derived Dyes in Photodynamic Therapy

Photodynamic therapy (PDT) is a method of cancer treatment that leads to the disintegration of cancer cells and has developed significantly in recent years. The clinically used photosensitizers are primarily porphyrin, which absorbs light in the red spectrum and their absorbance maxima are relatively short. This review presents group of compounds and their derivatives that are considered to be potential photosensitizers in PDT. Cyanine dyes are compounds that typically absorb light in the visible to near-infrared-I (NIR-I) spectrum range (750–900 nm). This meta-analysis comprises the current studies on cyanine dye derivatives, such as indocyanine green (so far used solely as a diagnostic agent), heptamethine and pentamethine dyes, squaraine dyes, merocyanines and phthalocyanines. The wide array of the cyanine derivatives arises from their structural modifications (e.g., halogenation, incorporation of metal atoms or organic structures, or synthesis of lactosomes, emulsions or conjugation). All the following modifications aim to increase solubility in aqueous media, enhance phototoxicity, and decrease photobleaching. In addition, the changes introduce new features like pH-sensitivity. The cyanine dyes involved in photodynamic reactions could be incorporated into sets of PDT agents.

AB0110 DETERMINING THE AMOUNT OF COPPER–CONTAINING PROTEIN, ITS BIOCHEMICAL AND IMMUNOLOGIC ACTIVITY IN RHEUMATOID ARTHRITIS PATIENTS

Background:Production of antibodies to ceruloplasmin (CP) in rheumatoid arthritis is an issue that has not been studied well enough. It was not by chance that this copper–containing alpha 2-glycorpoteid of blood plasma showing multienzymatic properties was chosen as an object of investigation. Data on the content and activity of CP in the blood of rheumatoid arthritis patients are contradictory, which has to do with different approaches to selection of patients and different measuring methods.Objectives:Improving diagnosis of rheumatoid arthritis by determination of antibodies to CP as well as its amount and enzymatic activity.Methods:We studied the serum from 30 apparently healthy individuals, and 108 rheumatoid arthritis patients. Antibodies to CP were determined by enzyme immunoassay using immobilized granulated antigen preparations (modification by Gontar et al, 2002). The amount of CP was determined by enzyme immunoassay according to the method of I.S. Kuzmina et al (1991) using commercial diagnostic agent manufactured by Mechnikov Research Institute for Vaccines and Sera.Results:Enzyme immunoassay showed a mean level of CP antibodies in donor sera of 0,020±0,006 optical density units. The level of normal values of specific antibodies determined as M±2σ included an extinction value in the range 0 – 0,086. The mean value of oxidase activity and the amount of CP in healthy people was 716±26,3 and 921±32 ng/ml, correspondingly. In the process of study we revealed a reliable increase in CP antibody count, the activity and amount of CP in patients with rheumatoid arthritis while in all cases the parameters under study correlated with the degree of disease activity (p<0,05): at activity degree I CP antibodies were 0,098±0,011; CP activity was 954±48,1; CP amount was 1292±73,4. At activity degree II CP antibodies were 0,138±0,007; CP activity was 1163±39,6; CP amount was 1763±69,3. At activity degree III, CP antibodies were 0,182±0,015; CP activity was 1368±89,5; CP amount was 1794±102,8. After a course of hospital treatment was completed, we noted a reliable decrease in the activity and amount of CP (at degree I of rheumatoid arthritis activity p<0,001, at degree II of rheumatoid arthritis activity p<0,01for both parameters; at degree III, p<0,05) compared with baseline findings. A decrease in CP antibodies shows decelerated dynamics, especially in patients with pronounced disease activity, which indicates severe disorders in the immunity that cannot be cured completely within 30 – 40 days of hospital treatment course.Conclusion:Determination of CP antibodies, as well as quantitative content of CP and its oxidase activity can serve as indicators of the activity of rheumatoid arthritis, as well as an accessory criterion of the effectiveness of administered therapy.Disclosure of Interests:None declared