scholarly journals Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery

2021 ◽  
Vol 8 (4) ◽  
pp. 43
Author(s):  
Jihoon Kim ◽  
Jee Seon Kim ◽  
Kyung Hyun Min ◽  
Young-Hwa Kim ◽  
Xiaoyuan Chen
Keyword(s):  
Blood Circulation ◽  
Burst Release ◽  
Oxygen Species ◽  
Antibody Drug Conjugate ◽  
Gastrin Releasing Peptide ◽  
Anticancer Effects ◽  
Efficient Delivery ◽  
Nanoparticle System ◽  
Micelle System

Dolastatin derivatives, represented by monomethylauristatin E (MMAE), have been translated in clinic with a form of antibody–drug conjugate; however, their potential in nanoparticle systems has not been well established due to the potential risk of immature release of extremely high cytotoxic dolastatin drugs during blood circulation. Herein, we rationally propose monomethylauristatin F (MMAF), a dolastatin-derived, loaded nanoparticle system composed of bombesin (BBN)-tethered ROS-responsive micelle system (BBN-PEG-PPADT) to achieve efficient anticancer therapy with targeted and efficient delivery of MMAF. The developed MMAF-loaded BBN-PEG-PPADT micelles (MMAF@BBN-PEG-PPADT) exhibited improved cellular uptake via interactions between BBN and gastrin-releasing peptide receptors on the cancer cells and the intracellular burst release of MMAF, owing to the ROS-responsive disruption, which allowed the efficient anticancer effects of MMAF in vitro. This study suggests the potential of nanoparticle systems in the delivery of dolastatin drugs.

scholarly journals Effects of Pterostilbene on the Activation of Nuclear Factor Erythroid 2-Related Factor 2 Pathway During in vitro Maturation of Mouse Oocytes

2018 ◽  
Vol 10 (7) ◽  
pp. 35
Author(s):  
Obaid Ullah ◽  
Li Zhongshu ◽  
Ihsan Ali ◽  
Lijie Xu ◽  
Haixing Liu ◽  
...  
Keyword(s):  
Protein Expression ◽  
In Vitro Maturation ◽  
Biological Activities ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Bcl2 Family ◽  
Mouse Oocytes ◽  
Anticancer Effects

Pterostilbene (PTS) is a natural polyphonic compound known to have biological activities, such as antioxidant and anticancer effects. This study was designed to regulate the effect of pterostilbene on the in vitro maturation (IVM) of mouse oocytes denuded of the cumulus (DOs). Different concentration of PTS was added to IVM media with immature DOs. After maturation, meiosis II (MII) stage rates oocytes, Measurement of reactive oxygen species (ROS) and glutathione (GSH) levels, activation of the Nuclear Factor Erythroid 2 like 2 (NFE2L2) pathway and apoptotic expression of BCL2 family in MII oocytes were determined. Our results showed that: PTS significantly increased the MII rate of DOs (P < 0.05). Moreover, PTS decreased the ROS levels in DOs (P < 0.05) and increased the GSH levels (P < 0.05). Furthermore, PTS addition in DOs significantly increased the protein expression of NFE2L2 in the nucleus and decreased Kelch-like ECH-associated protein1 (KEAP1). PTS significantly increased the antioxidant enzyme expression of catalase (CAT), heme oxygenase1 (HMOX1), and superoxide dismutase (SOD). In addition, PTS lowered the protein expression of apoptotic Bcl-2-associated X protein (BAX) and increased the protein expression of anti-apoptotic B-cell lymphoma2 (BCL2) as well as PTS treatment significantly increased the gene expression of BCL2 and reduced the expression of apoptotic BAX in matured DOs. These results indicated that pterostilbene significantly improved the IVM quality matured of DOs and activate NFE2L2-Keap1 pathway during maturation of oocytes.

Preparation and In Vitro Evaluation of Resealed Erythrocytes as A New Trend in Treatment of Asthma

2016 ◽  
Vol 6 (3) ◽  
Author(s):  
Mohammed Ibrahim ◽  
Alaa Zaky ◽  
Mohsen Afouna ◽  
Ahmed Samy
Keyword(s):  
In Vitro Release ◽  
Human Erythrocytes ◽  
The Body ◽  
Blood Levels ◽  
Time Interval ◽  
Burst Release ◽  
Prolonged Release ◽  
Nocturnal Asthma ◽  
Carrier Erythrocytes

Carrier erythrocytes are emerging as one of the most promising biological drug delivery systems investigated in recent decades. Beside its biocompatibility, biodegradability and ability to circulate throughout the body, it has the ability to perform extended release system of the drug for a long period. The ultimate goal of this study is to introduce a new carrier system for Salbutamol, maintaining suitable blood levels for a long time, as atrial to resolve the problems of nocturnal asthma medication Therefore in this work we study the effect of time, temperature as well as concentration on the loading of salbutamol in human erythrocytes to be used as systemic sustained release delivery system for this drug. After the loading process is performed the carrier erythrocytes were physically and cellulary characterized. Also, the in vitro release of salbutamol from carrier erythrocytes was studied over time interval. From the results it was found that, human erythrocytes have been successfully loaded with salbutamol using endocytosis method either at 25 Co or at 37 Co . The highest loaded amount was 3.5 mg/ml and 6.5 mg/ml respectively. Moreover, the percent of cells recovery is 90.7± 1.64%. Hematological parameters and osmotic fragility behavior of salbutamol loaded erythrocytes were similar that of native erythrocytes. Scanning electron microscopy demonstrated that the salbutamol loaded cells has moderate change in the morphology. Salbutamol releasing from carrier cell was 43% after 36 hours in phosphate buffer saline. The releasing pattern of the drug from loaded erythrocytes showed initial burst release in the first hour followed by a very slow release, obeying zero order kinetics. It concluded that salbutamol is successfully entrapped into erythrocytes with acceptable loading parameters and moderate morphological changes, this suggesting that erythrocytes can be used as prolonged release carrier for salbutamol.

Internal and External Triggering Mechanism of “Smart” Nanoparticle-Based DDSs in Targeted Tumor Therapy

2018 ◽  
Vol 24 (15) ◽  
pp. 1639-1651 ◽  
Author(s):  
Xian-ling Qian ◽  
Jun Li ◽  
Ran Wei ◽  
Hui Lin ◽  
Li-xia Xiong
Keyword(s):  
Targeted Delivery ◽  
Tumor Therapy ◽  
Burst Release ◽  
Tumor Site ◽  
Chemotherapeutic Drugs ◽  
Triggering Mechanism ◽  
Triggering Factors ◽  
Or Genes

Background: Anticancer chemotherapeutics have a lot of problems via conventional Drug Delivery Systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: “passive”, “active”, and “smart” targeting. Objective: To summarize the mechanisms of various internal and external “smart” stimulating factors on the basis of findings from in vivo and in vitro studies. Method: A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Results: Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), “smart” DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. Conclusion: In this review article, we summarize and classify the internal and external triggering mechanism of “smart” nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding.

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Vegf Signaling ◽  
Anticancer Effects ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

Nanocurcumin: A Double-Edged Sword for Microcancers

2020 ◽  
Vol 26 (45) ◽  
pp. 5783-5792
Author(s):  
Kholood Abid Janjua ◽  
Adeeb Shehzad ◽  
Raheem Shahzad ◽  
Salman Ul Islam ◽  
Mazhar Ul Islam
Keyword(s):  
Intracellular Signaling ◽  
Dosage Forms ◽  
The Body ◽  
In Vivo Studies ◽  
Mrna Levels ◽  
Anticancer Activities ◽  
Road Map ◽  
Anticancer Effects

There is compelling evidence that drug molecules isolated from natural sources are hindered by low systemic bioavailability, poor absorption, and rapid elimination from the human body. Novel approaches are urgently needed that could enhance the retention time as well as the efficacy of natural products in the body. Among the various adopted approaches to meet this ever-increasing demand, nanoformulations show the most fascinating way of improving the bioavailability of dietary phytochemicals through modifying their pharmacokinetics and pharmacodynamics. Curcumin, a yellowish pigment isolated from dried ground rhizomes of turmeric, exhibits tremendous pharmacological effects, including anticancer activities. Several in vitro and in vivo studies have shown that curcumin mediates anticancer effects through the modulation (upregulation and/or downregulations) of several intracellular signaling pathways both at protein and mRNA levels. Scientists have introduced multiple modern techniques and novel dosage forms for enhancing the delivery, bioavailability, and efficacy of curcumin in the treatment of various malignancies. These novel dosage forms include nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated polymer nanoparticles. Nanocurcumin has shown improved anticancer effects compared to conventional curcumin formulations. This review discusses the underlying molecular mechanism of various nanoformulations of curcumin for the treatment of different cancers. We hope that this study will make a road map for preclinical and clinical investigations of cancer and recommend nano curcumin as a drug of choice for cancer therapy.

Injectable in-situ Forming Depot Of Doxycycline Hyclate/α-Cyclodextrin Complex using PLGA for Periodontitis Treatment: Preparation, Charac-terization, and In-Vitro Evaluation

2020 ◽  
Vol 17 ◽  
Author(s):  
Elham Khodaverdi ◽  
Farhad Eisvand ◽  
Mohammad Sina Nezami ◽  
Seyedeh Nesa Rezaeian Shiadeh ◽  
Hossein Kamali ◽  
...  
Keyword(s):  
Complex Form ◽  
Docking Studies ◽  
Morphological Properties ◽  
Burst Release ◽  
Cyclodextrin Complex ◽  
Doxycycline Hyclate ◽  
Scanning Calorimetry ◽  
In Situ Forming

Background:: Doxycycline (DOX) is used in treating a bacterial infection, especially for periodontitis treatment. Objective: To reduce irritation of DOX for subgingival administration and increase the chemical stability and against enzy-matic, the complex of α-cyclodextrin with DOX was prepared and loaded into injectable in situ forming implant based on PLGA. Methods:: FTIR, molecular docking studies, X-ray diffraction, and differential scanning calorimetry was performed to char-acterize the DOX/α-cyclodextrin complex. Finally, the in-vitro drug release and modeling, morphological properties, and cellular cytotoxic effects were also evaluated. Results:: The stability of DOX was improved with complex than pure DOX. The main advantage of the complex is the al-most complete release (96.31 ± 2.56 %) of the drug within 14 days of the implant, whereas in the formulation containing the pure DOX and the physical mixture the DOX with α-cyclodextrin release is reached to 70.18 ± 3.61 % and 77.03 ± 3.56 %, respectively. This trend is due to elevate of DOX stability in the DOX/ α-cyclodextrin complex form within PLGA implant that confirmed by the results of stability. Conclusion:: Our results were indicative that the formulation containing DOX/α-cyclodextrin complex was biocompatible and sustained-release with minimum initial burst release.

scholarly journals Internalization of Foldamer-Based DNA Mimics through a Site-Specific Antibody Conjugate to Target HER2-Positive Cancer Cells

2021 ◽  
Vol 14 (7) ◽  
pp. 624
Author(s):  
Valentina Corvaglia ◽  
Imène Ait Mohamed Amar ◽  
Véronique Garambois ◽  
Stéphanie Letast ◽  
Aurélie Garcin ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Topoisomerase I ◽  
Ovarian Cancer Cells ◽  
Cellular Functions ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Dna Topoisomerase ◽  
Antibody Conjugate ◽  
A Site

Inhibition of protein–DNA interactions represents an attractive strategy to modulate essential cellular functions. We reported the synthesis of unique oligoamide-based foldamers that adopt single helical conformations and mimic the negatively charged phosphate moieties of B-DNA. These mimics alter the activity of DNA interacting enzymes used as targets for cancer treatment, such as DNA topoisomerase I, and they are cytotoxic only in the presence of a transfection agent. The aim of our study was to improve internalization and selective delivery of these highly charged molecules to cancer cells. For this purpose, we synthesized an antibody-drug conjugate (ADC) using a DNA mimic as a payload to specifically target cancer cells overexpressing HER2. We report the bioconjugation of a 16-mer DNA mimic with trastuzumab and its functional validation in breast and ovarian cancer cells expressing various levels of HER2. Binding of the ADC to HER2 increased with the expression of the receptor. The ADC was internalized into cells and was more efficient than trastuzumab at inhibiting their growth in vitro. These results provide proof of concept that it is possible to site-specifically graft high molecular weight payloads such as DNA mimics onto monoclonal antibodies to improve their selective internalization and delivery in cancer cells.

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