Side Effects Of Anticancer Drugs Research Articles

Controlled release of anticancer drugs via the magnetic magnesium iron nanoparticles modified by graphene oxide and polyvinyl alcohol: Paclitaxel and docetaxel

Objective(s)Paclitaxel (PTX) and docetaxel (DTX) belong to the family of taxanes drugs which have been employed for treatment of ovarian, breast, lung, head, neck, gastric, pancreatic, bladder, prostate and cervical cancer. Controlled drug release systems improve the effectiveness of drug therapy by modifying the release profile, biodistribution, stability and solubility, bioavailability of drugs and minimize the side effects of anticancer drugs. So, the purpose of the present study was to synthesize the modified nanocomposite for the controlled releases of these drugs.Materials and MethodsMagnetic magnesium iron oxide nanoparticles were synthesized via the co-precipitation chemical method and then composited with graphene oxide and modified by polyvinyl alcohol. The physicochemical characterization of the prepared nanocomposites was investigated by scanning electron microscope (SEM), X-ray powder diffraction (XRD) , Fourier-transform infrared spectroscopy and vibrating-sample magnetometer.ResultsSpecific characteristics such as adsorption capacity, monodispersity, stability and hydrophilicity of magnetic nanomaterials were studied in the controlled release of anticancer drugs. Drug loading content and drug loading efficiency and release rate of drugs were investigated in vitro at different pH with ultraviolet-visible spectroscopy (UV-Vis). DLE and DLC of PTX and DTX in the modified magnetic nanocomposites were calculated as 85.2 ± 2.7% and 7.74 ± 0.24% , 89.4 ± 1.2% and 8.12 ± 0.11% of, respectively. The cumulative release amount of PTX and DTX from magnetic modified nanocomposites at pHs 5.8, 7.4 over 100 h were 58 % and 40 % and 54 % and 37 %, respectively.ConclusionThe potential of modified nanocomposite in drug delivery systems from the intrinsic properties of the magnetic core combined with their drug loading capability and the biomedical properties of modified nanocomposite generated by different surface coatings. The generally sustained and controlled release profile of DTX (or PTX) facilitates the application of modified nanocomposite for the delivery of anticancer drugs.

Polypharmacy and Malnutrition Management of Elderly Perioperative Patients with Cancer: A Systematic Review.

Malnutrition, which commonly occurs in perioperative patients with cancer, leads to decreased muscle mass, hypoalbuminemia, and edema, thereby increasing the patient’s risk of various complications. Thus, the nutritional management of perioperative patients with cancer should be focused on to ensure that surgical treatment is safe and effective, postoperative complications are prevented, and mortality is reduced. Pathophysiological and drug-induced factors in elderly patients with cancer are associated with the risk of developing malnutrition. Pathophysiological factors include the effects of tumors, cachexia, and anorexia of aging. Metabolic changes, such as inflammation, excess catabolism, and anabolic resistance in patients with tumor-induced cancer alter the body’s ability to use essential nutrients. Drug-induced factors include the side effects of anticancer drugs and polypharmacy. Drug–drug, drug–disease, drug–nutrient, and drug–food interactions can significantly affect the patient’s nutritional status. Furthermore, malnutrition may affect pharmacokinetics and pharmacodynamics, potentiate drug effects, and cause side effects. This review outlines polypharmacy and malnutrition, the impact of malnutrition on drug efficacy, drug–nutrient and drug–food interactions, and intervention effects on polypharmacy or cancer cachexia in elderly perioperative patients with cancer.

Doxorubicin-loaded gold nanorods: a multifunctional chemo-photothermal nanoplatform for cancer management.

Two of the limitations associated with cancer treatment are the low efficacy and the high dose-related side effects of anticancer drugs. The purpose of the current study was to fabricate biocompatible multifunctional drug-loaded nanoscale moieties for co-therapy (chemo-photothermal therapy) with maximum efficacy and minimum side effects. Herein, we report in vitro anticancerous effects of doxorubicin (DOX) loaded on gold nanorods coated with the polyelectrolyte poly(sodium-4-styrenesulfonate) (PSS-GNRs) with and without NIR laser (808 nm, power density = 1.5 W/cm2 for 2 min) irradiation. The drug-loading capacity of PSS-GNRs was about 76% with a drug loading content of 3.2 mg DOX/mL. The cumulative DOX release significantly increased after laser exposure compared to non-irradiated samples (p < 0.05). The zeta potential values of GNRs, PSS-GNRs and DOX-PSS-GNRs were measured as 42 ± 0.1 mV, −40 ± 0.3 mV and 39.3 ± 0.6 mV, respectively. PSS-GNRs nanocomplexes were found to be biocompatible and showed higher photothermal stability. The DOX-conjugated nanocomplexes with NIR laser irradiation appear more efficient in cell inhibition (93%) than those without laser exposure (65%) and doxorubicin alone (84%). The IC50 values of PSS-GNRs-DOX and PSS-GNRs-DOX were measured as 7.99 and 3.12 µg/mL, respectively, with laser irradiation. Thus, a combinatorial approach based on chemotherapy and photothermal strategies appears to be a promising platform in cancer management.

2. Establishing Preventive Strategies Against the Side Effects of Anticancer Drugs Using the Medical Large Databases of Spontaneous Adverse Event Reports

2. Establishing Preventive Strategies Against the Side Effects of Anticancer Drugs Using the Medical Large Databases of Spontaneous Adverse Event Reports

Evaluation of Sleep Training Effectiveness on the Quality of Sleep in Cancer Patients during Chemotherapy.

Background:Sleep disorder is one of the most common problems in cancer patients involved in chemotherapy stages, which is caused by the side effects of anticancer drugs and the exacerbation of mental disorders. The aim of this study was to evaluate the effectiveness of sleep health education on sleep quality of cancer patients during chemotherapy stages.Materials and Methods:In this clinical trial, 70 cancer patients were selected in the chemotherapy phase and divided into two groups of 35. In the intervention group, two 60-min training sessions on sleep hygiene were educated, solutions of coping with the exacerbation of sleep disturbances were determined, and routine care was provided in the control group. Patients were evaluated for sleep disorders before and 1 and 3 weeks after the intervention by the Pittsburgh questionnaire and then the effect of this intervention compared between the two groups.Results:The mean score of sleep medication consumption in the intervention group was not significantly different between the three times (P = 0.59), but the mean score of total sleep quality disorder and its other dimensions was significantly different between the three time points (P < 0.05). Least significant difference post hoc test showed that the mean total score of sleep quality disorder and its dimensions except using sleep medication 1 week after the intervention was significantly less than before the intervention and 3 weeks after the intervention <1 week after the intervention in the intervention group (P < 0.05).Conclusion:Sleep health education for cancer patients involved in chemotherapy can significantly have a positive effect on improving their sleep quality.

The Effects of Curcumin on the Side Effects of Anticancer Drugs in Chemotherapy: A Randomized Controlled Trial.

Curcumin, the active ingredient of the spice turmeric, has been shown to have anticancer activities in several preclinical and clinical studies. The prophylactic effect of curcumin against chemotherapy-induced damage and side effects was evaluated in a double-blind, placebo-controlled randomized trial. Eighty cancer patients on standard chemotherapy regimens were randomly assigned to receive curcumin as adjuvant therapy (500 mg per 12hours) and matched control group to receive placebo for 9weeks. Pre- and post-intervention, the changes in the health-related quality-of-Life (QoL) score (based on the University of Washington Quality-of-Life (UW-QoL) questionnaire, version 3), clinical symptoms, and hematological and biochemical parameters were assessed. Comparison between groups based on total QoL score showed that curcumin supplementation was not associated with improved QoL (P=0.102). Hematological and biochemical analysis showed no statistical differences between the groups at the end of the trial (P>0.05). However, during the trial, significant differences were observed in hemoglobin (Hb), hematocrit (HCT), lactic acid dehydrogenase (LDH), serum glutamic-oxaloacetic transaminase (SGOT), and anaplastic lymphoma kinase (ALK) between the groups (P<0.05). Future studies in a larger homogenous population of cancer patients are required to confirm the adjuvant effect of curcumin on chemotherapy-induced QoL.

Correction possibilities of drug-induced liver toxicity in the treatment of patients with blood system tumors

Background. In modern oncohematology achieved notable success due to the intensification and development of new chemotherapy regimens. However, the side effects of anticancer drugs, due to low selectivity of most of them, are a serious limitation to achieve their maximal therapeutic effect. Although doctors are aware of the possibility of hepatotoxic reactions to various drugs, in clinical practice, the diagnosis of drug-induced liver injury is formulated unreasonably rarely. This speculation is due to several factors: in some cases, the latent course of drug-induced liver injury, often inadequate interpretation of clinical symptoms and laboratory parameters, and sometimes insufficiently thorough collection of anamnesis. A particularly difficult problem for a doctor is the development of drug-induced hepatotoxicity in patients for whom the “causal” drug is prescribed for vital indications, in particular, polychemotherapy in cancer patients, complex antimicrobial therapy and antiviral therapy for febrile neutropenia or sepsis, etc. In these situations, on the one hand, treatment cancellation is impossible due to the risk of disease progression, on the other hand, its continuation is undesirable due to the risk of severe hepatitis. In addition, multicomponent therapy, which is a complex of potentially hepatotoxic substances, often does not allow specifying the substance that caused the pathological reaction. At the same time, it is obvious that the hepatocyte, the main cell of the hepatic parenchyma, remains the center of the organ pathology. The variety of biochemical processes occurring with ademetionine participation served as the basis for conducting clinical studies in order to correct drug-induced liver toxicity in the treatment of patients with blood system tumors.The objective of the study is to assess laboratory and clinical parameters of drug-induced liver injury (DILI), intrahepatic cholestasis in the study of homeostasis disorders in patients with hematological malignancies and chemotherapy-induced hepatotoxicity.Materials and methods. The study involved 45 patients with blood system tumors, who had chemotherapy-induced hepatocellular failure. To describe the population of DILI patients, we collected demographic data, clarified the underlying liver disease in each patient, and analyzed the diagnostic criteria for chronic liver disease due to DILI. Clinical signs and symptoms of cholestasis (jaundice, pruritus, weakness), as well as manifestations of a depressive state and asthenic syndrome – mood (mild, moderate and severe), normalization of sleep rhythm, memory improvement, general health were assessed. Changes in laboratory parameters of liver function were studied. In 20 patients with blood system tumors, the biochemical parameters associated with cell metabolism were analyzed – lipid peroxidation, nitric oxide (NOx ) level, impaired liver detoxification capacity by glutathione level and glutathione-S-transferase activity. The treatment regimens for drug-induced hepatotoxicity included the Heptral, which was prescribed until stable normalization of liver function.Results. All patients with developed liver failure showed metabolic disorders. The use of ademetionine has shown significant effect. The NO and superoxide dismutase in most patients decreased significantly and almost corresponded to the norm. Normalization of the glutathione system parameters was also observed. One of the mechanisms of Heptral protective effect is an increase in the glutathione synthesis. The improvement in laboratory parameters was accompanied by the disappearance of DILI and intrahepatic cholestasis symptoms. This is confirmed by significant statistical correlations between them and indicates the ademetionine efficacy to recovery of hepatocytes function. When using ademetionine, the most pronounced reduction among biochemical parameters was observed in alkaline phosphatase and γ-glutamyl transpeptidase, markers of cholestasis syndrome. In addition, serum bilirubin concentration and alanine and aspartic transaminases activity (albeit to a lesser extent) decreased significantly. Clinical and biochemical effects, as a rule, persisted for several months after completion of therapy. Decrease in biochemical parameters characterizing cholestasis and cytolysis (positive dynamics of alanine and aspartic transaminases, alkaline phosphatase, γ-glutamyl transpeptidase, bilirubin) was accompanied by an improvement and normalization of patients’ well-being. When assessing the depression and asthenic syndrome, it was noted that the duration of Heptral therapy is important.Conclusion. The results obtained were the basis for the development of supportive therapy programs to prevent and reduce liver toxicity during chemotherapy. Rational approaches to the liver metabolic disorders correction – a real way to increase the treatment efficacy and improve the quality of life of patients with blood system tumors.

Design and Construction of Ph-Sensitive Drug Delivery System Based on Metal-Organic Framework (MOF) Nanoparticles for Cancer Treatment by Drug Delivery System Containing Curcumin

Introduction: Much research has been carried out to improve drug delivery and targeted drug delivery to the body in order to minimize side effects, provide controlled delivery of the drug to the desired location and to achieve optimal therapeutic effects. Zeolitic imidazolate-8 (ZIF-8) is a subset of MOFs that are biocompatible, stable in the aquatic environment and have adjustable porosity. In addition, at pHs 5 or 6, the bond between imidazolate-zinc ions disappears and releases the drug. In this project, ZIF-8 was used as a curcumin carrier to improve the physicochemical properties and enhance the efficacy of lipophilic drugs in the treatment of cancer.&#x0D; Methods: This research was a basic experimental study. ZIF-8 nanoparticles were fabricated by co-precipitation method. In addition, to prove their pH sensitivity, curcumin was first encapsulated in situ in ZIF-8 and characterized by XRD, SEM, TEM, DLS methods. Then its release was investigated at two pH of five and 7.4 saline phosphate buffer. Finally, In vitro study by MTT assay was performed on prostate cancer cell line (PC3). Data were compared by analysis of variance (ANOVA) using SPSS version 16 software.&#x0D; Results: After characterization of the nanoparticles by the mentioned methods, it was found that the nanoparticle dimensions were between 80-60 nm and the nanoparticle dimensions with curcumin were between 120-110 nm. In addition, in the synthesis of ZIF-8 nanoparticles, %72 of the drug was loaded, which is an acceptable amount.&#x0D; Conclusion: These nanoparticles showed high capacity in the treatment of prostate cancer and minimal damage to healthy cells. It can be said that using this formulation for targeted drug delivery of cancer not only reduces the side effects of anti-cancer drugs but also increases their effectiveness and can also be used to deliver low-soluble or insoluble drugs in biological environments.

The Study of the Protective Effect of Vitamin E and Retinoic Acid on Testicular Tissue in Mice Treated with Cyclophosphamide

Background and Aim: One of the side effects of anticancer drugs is spermatogenesis disorder. Hence, the evaluation of sperm production after chemotherapy has been the subject of several studies today. Methods: Adult male albino mice weighing 20±2 g were randomly divided into 5 groups (n = 4);control, cyclophosphamide (12 mg/kg/day), cyclophosphamide and vitamin E (200 mg/kg/day), cyclophosphamide and retinoic acid (500 µL/72h), cyclophosphamide and retinoic acid (250 µL/72h) and vitamin E (100 mg/day). The treatment was continued for 35 days and at the end of the rats was anesthetized and testicular tissue was isolated, weighed, fixed, and stained with hematoxylin-eosin. Results: A significant decrease (p-value ≤ 0.0001) in the mean diameter of seminal vesicles, epithelial thickness, and index of tubular differentiation was observed in the testis tissue of mice treated with cyclophosphamide compared to the control group. In cyclophosphamide recipients with retinoic acid or vitamin E, parameters significantly increased to the level of the control group (p-value ≤ 0.0001), whereas cyclophosphamide co-administration with retinoic acid and vitamin A had a less tissue-protective effect. Conclusion: Vitamin E and retinoic acid can offset the adverse effects of cyclophosphamide on spermatogenesis and may be inducers of spermatogenesis, while the combination of these two antioxidants has fewer efficacies. *Corresponding Author: Fatemeh Sadat Moravej; Email: akbar.karimi@es.isfpnu.ac.ir Please cite this article as: Karimi A, Behmard V, Toghiani S, Moravej FS. The Study of the Protective Effect of Vitamin E and Retinoic Acid on Testicular Tissue in Mice Treated with Cyclophosphamide. Arch Med Lab Sci. 2020;6:1-8 (e9). https://doi.org/10.22037/amls.v6.31520

抗がん剤副作用情報の入手に関する経験と患者の服薬調節行動の関連性

抗がん剤副作用情報の入手に関する経験と患者の服薬調節行動の関連性

Effect of Tussilago farfara L. Polysaccharides on the Content of Hematopoietic Stem Cells (CD117+34+) in the Bone Marrow of Mice Treated with Cyclophosphamide

Myelotoxicity is a serious side effect of anticancer drugs. The search for drugs that can reduce the hematological complications of chemotherapy through modulation of hematopoietic stem cells is an urgent task of oncopharmacology. In the present study we showed that administration of Tussilago farfara L. polysaccharides to C57BL/6 mice treated with cyclophosphamide can increase the number of hematopoietic stem cells (CD117+34+) in the bone marrow.

Targeted nano-sized drug design in cancer treatments: development of new nano-sized formulations for the use of anti-cancerogenic lisinopril in the treatment of colorectal cancer

Background: Colorectal cancer emerges as a serious health problem all over the world and results in approximately 700,000 deaths every year. Therefore, studies are carried out to develop alternative treatment methods to reduce the side effects of anticancer drugs in cancer treatment. Targeted nanoparticle therapies are tried to be developed especially with controlled drug release. Lisinopril, an angiotensin-converting enzyme inhibitor, is a widely used drug in the treatment of hypertension and has been shown to have anticancer activity on various types of cancer.Methods: This study, blank and 3 different amounts of lisinopril loaded nanoparticles were prepared by triblock poly (lactic acid)–poly (ethylene glycol)–poly (lactic acid) (PLA-PEG-PLA) block copolymer which is a biocompatible and biodegradable polymer by using water/oil/water emulsion method and then characterized. The viability of the blank formulations in murine fibroblast (L929) cells, which is the healthy cell line, was determined within the scope of biocompatibility studies.Results: The anticarcinogenic activity of lisinopril drug, blank and lisinopril loaded nanoparticles was determined in caco-2 cells which are human epithelial colorectal adenocarcinoma cell line.Conclusions: Lisinopril loaded nanoparticles were successfully prepared in this study. It is thought that increasing the amount of drug-loaded can be a promising approach to an alternative treatment method for the use of antihypertensive drugs in the treatment of colorectal cancer.

Antinociceptive role of neurotensin receptor 1 in rats with chemotherapy-induced peripheral neuropathy.

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of anti-cancer drugs. Neurotensin receptors (NTSRs) are widely distributed within the pain circuits in the central nervous system. The purpose of this study was to determine the role of NTSR1 by examining the effects of an NTSR1 agonist in rats with CIPN and investigate the contribution of spinal serotonin receptors to the antinociceptive effect.MethodsSprague–Dawley rats (weight 150–180 g) were used in this study. CIPN was induced by injecting cisplatin (2 mg/kg) once a day for 4 days. Intrathecal catheters were placed into the subarachnoid space of the CIPN rats. The antiallodynic effects of intrathecally or intraperitoneally administered PD 149163, an NTSR1 agonist, were evaluated. Furthermore, the levels of serotonin in the spinal cord were measured by high-performance liquid chromatography.ResultsIntrathecal or intraperitoneal PD 149163 increased the paw withdrawal threshold in CIPN rats. Intrathecal administration of the NTSR1 antagonist SR 48692 suppressed the antinociceptive effect of PD 149163 given via the intrathecal route, but not the antinociceptive effect of intraperitoneally administered PD 149163. Intrathecal administration of dihydroergocristine, a serotonin receptor antagonist, suppressed the antinociceptive effect of intrathecally administered, but not intraperitoneally administered, PD 149163. Injecting cisplatin diminished the serotonin level in the spinal cord, but intrathecal or intraperitoneal administration of PD 149163 did not affect this reduction.ConclusionsNTSR1 played a critical role in modulating CIPN-related pain. Therefore, NTSR1 agonists may be useful therapeutic agents to treat CIPN. In addition, spinal serotonin receptors may be indirectly involved in the effect of NTSR1 agonist.

Abstract 499: Modeling Carfilzomib Induced Cardiotoxicity Using Human Induced Pluripotent Stem Cell-derived Cardiomyocytes

Cardiovascular toxicity post Carfilzomib (Cfz/Kyprolis) therapy has been identified in several clinical settings. A prevalent challenge in side effects of anti-cancer drugs is the translation of findings from preclinical research into clinical practice. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are being used as a physiological in vitro model to overcome some of these challenges. Here we used both 2D and 3D hiPSC-CMs to elucidate the underlying mechanism of post-Cfz cardiotoxicity. hiPSC-CMs were exposed to clinically relevant doses of Cfz based on C max for Cfz (5.88 μM). Data normalization against the control group demonstrates significant reduction in cell viability following two days of treatment with Cfz in 3 different cell lines (IMR-90, SCVI273 and 902). Increased Caspase3/7 activity post Cfz treatment paralleled with a substantial decrease in mitochondrial membrane potential and increase in oxidative stress following Cfz treatment. Also, significant decrease in oxygen consumption rate was observed after one-day exposure. In addition, we observed impaired Ca 2+ handling at the single cell level following Cfz treatment. Using video microscopy with motion vector analysis we also observed significant decrease in contractility of 3D hiPSC-CMs following Cfz treatment. Additionally, we observed disrupted expression of α-actinin, alterations in structural organization of sarcomeres, circularity and aspect ratio. Altogether, these results suggest that Cfz induced cardiotoxicity as indicated by cell viability, oxidative stress, mitochondrial and structural damages along with abnormal Ca 2+ handing and contractility dysfunction.

Polymer-Graphene Nanoassemblies and their Applications in Cancer Theranostics.

Graphene-based nanomaterials have received increasing attention due to their unique physical-chemical properties including two-dimensional planar structure, large surface area, chemical and mechanical stability, superconductivity and good biocompatibility. On the other hand, graphene-based nanomaterials have been explored as theranostics agents, the combination of therapeutics and diagnostics. In recent years, grafting hydrophilic polymer moieties have been introduced as an efficient approach to improve the properties of graphene-based nanomaterials and obtain new nanoassemblies for cancer therapy. This review would illustrate biodistribution, cellular uptake and toxicity of polymergraphene nanoassemblies and summarize part of successes achieved in cancer treatment using such nanoassemblies. The observations showed successful targeting functionality of the polymer-GO conjugations and demonstrated a reduction of the side effects of anti-cancer drugs for normal tissues.

Simultaneous Delivery of antimiR-21 and Doxorubicin by Graphene Oxide for Reducing Toxicity in Cancer Therapy

Graphene oxide (GO) has been studied by many researchers for its potential drug-delivery value. In order to reduce the side effects of anticancer drugs by decreasing the dosage and maintain the therapeutic effects, a dual drug-delivery system that used GO as a carrier and simultaneously loaded with antitumor drugs and antimir-21 was rationally designed for the cooperative treatment of tumors. Results obtained from our studies have found that MDA-MB-231 cells were inhibited in low Dox dose. The outcomes of confocal microscopy indicated that Dox and antimiR-21 could be released rapidly in cancer cells, which is good for killing cancer cells. In addition, qRT-PCR further demonstrated that miR-21 was silenced by antimiR-21. Consequently, GO has a great potential to codeliver chemotherapeutic drugs and gene drugs in cancer combination therapy for reducing toxicity.

Macromolecular Prodrugs Containing Organoiron-Based Compounds in Cancer Research: A Review.

Among the methods used for the treatment of cancer, chemotherapy is widely used, and it is by far one of the most unpleasant procedures given to a patient because of its severe side effects; while being necessary. One of the major problems in cancer chemotherapy is the limited selectivity of most of the drugs in current clinical use. Following administration, the active agent is distributed over the entire body and reaches not only the target cells or tissues but also interacts with healthy cells. In an attempt to overcome the side effects of anticancer drugs, the modification of the anticancer bioactive compounds has been a topic of active research for years. Numerous delivery systems such as drugcontaining liposomes, microencapsulation, nanoparticles, and water-soluble polymers have been used for the delivery of bioactive compounds to the site of action. Water-soluble polymeric conjugates and co-conjugates have remained the most outstanding delivery technique. This review will discuss the development of polymeric conjugates and co-conjugates of ferrocene in cancer research.

The impact of blue light in monolayers representing tumorigenic and nontumorigenic cell membranes containing epigallocatechin-3-gallate

Natural products such as epigallocatechin-3-gallate (EGCG) have been suggested for complementary treatments of cancer, since they lower toxic side effects of anticancer drugs, and possess anti-inflammatory and antioxidant properties that inhibit carcinogenesis. Their effects on cancer cells depend on interactions with the membrane, which is the motivation to investigate Langmuir monolayers as simplified membrane models. In this study, EGCG was incorporated in zwitterionic dipalmitoyl phosphatidyl choline (DPPC) and anionic dipalmitoyl phosphatidyl serine (DPPS) Langmuir monolayers to simulate healthy and cancer cells membranes, respectively. EGCG induces condensation in surface pressure isotherms for both DPPC and DPPS monolayers, interacting mainly via electrostatic forces and hydrogen bonding with the choline and phosphate groups of the phospholipids, according to data from polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). Both monolayers become more compressible upon interaction with EGCG, which may be correlated to the synergy between EGCG and anticancer drugs reported in the literature. The interaction with EGCG is stronger for DPPC, leading to stronger morphological changes in Brewster angle microscopy (BAM) images and higher degree of condensation in the surface pressure isotherms. The changes induced by blue irradiation on DPPC and DPPS monolayers were largely precluded when EGCG was incorporated, thus confirming its antioxidant capacity for both types of membrane.

Folate Receptor Targeting and Cathepsin B-Sensitive Drug Delivery System for Selective Cancer Cell Death and Imaging.

In this work, a folate receptor (FR)-mediated dual-targeting drug delivery system was synthesized to improve the tumor-killing efficiency and inhibit the side effects of anticancer drugs. We designed and synthesized an FR-mediated fluorescence probe (FA-Rho) and FR-mediated cathepsin B-sensitive drug delivery system (FA-GFLG-SN38). FA-GFLG-SN38 is composed of the FR ligand (folic acid, FA), the tetrapeptide substrate for cathepsin B (GFLG), and an anticancer drug (SN38). The rhodamine B (Rho)-labeled probe FA-Rho is suitable for specific fluorescence imaging of SK-Hep-1 cells overexpressing FR and inactive in FR-negative A549 and 16-HBE cells. FA-GFLG-SN38 exhibited strong cytotoxicity against FR-overexpressing SK-Hep-1, HeLa, and Siha cells, with IC50 values of 2-3 μM, but had no effect on FR-negative A549 and 16-HBE cells. The experimental results show that the FA-CFLG-SN38 drug delivery system proposed by us can effectively inhibit tumor proliferation in vitro, and it can be adopted for the diagnostics of tumor tissues and provide a basis for effective tumor therapy.

Novel selective anticancer agents based on Sn and Au complexes. Mini-review

Abstract Cancer is one of the most common causes of death in modern medicine. Molecular design of novel substances with pharmacological activity is one of the goals of medicinal inorganic chemistry. Platinum complexes are widely used in the treatment of cancer, despite high efficacy their use is limited by side effects, as well as primary or acquired resistance. In this regard, the search for novel metal-containing antitumor compounds is underway. Organotins and gold compounds are promising pharmacological agents with anti-cancer properties. The introduction of protective antioxidant fragments into inorganic compounds molecules is a way to reduce the side effects of anti-cancer drugs on healthy cells. 2,6-dialkylphenols belonging to vitamin E (α-tocopherol) mimetics are widely used as antioxidants and stabilizers. The properties of Ph3SnCl (Sn-I), Ph3PAuCl (Au-I) and complexes Ph3SnSR (Sn-II) and Ph3PAuSR (Au-II) based on 2,6-di-tert-butyl-4-mercaptophenol (RSH) as radical scavengers and reducing agents were studied in model reactions. For Sn-II and Au-II the comparative study of cytotoxic action was made and the IC50 values on different cancer cell lines were found to be depended on the nature of metal. In general, Sn(IV) complexes possessed higher cytotoxicity than Au(I) complexes. In order to clarify the mechanism of cytotoxic mode of action the effect of compounds on Fe3+-induced lipid peroxidation, mitochondrial potential and mitochondrial permeability, cell cycle and induction of apoptosis was studied. Organotin compounds can bind tubulin SH-groups and inhibit its polymerization by a dose-dependent mechanism, whereas gold compounds inhibit Thioredoxin reductase (TrxR). In vivo experiments on acute toxicity of Sn-II and Au-II proved their moderate toxic action that opens prospects for the further study as antitumor agents.