scholarly journals Enhanced Subcellular Trafficking of Resveratrol Using Mitochondriotropic Liposomes in Cancer Cells

Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 423 ◽  
Author(s):  
Ji Hee Kang ◽  
Young Tag Ko
Keyword(s):  
Polyethylene Glycol ◽  
Cancer Cells ◽  
Behavioral Observation ◽  
Multi Drug Resistance ◽  
Cancer Cell Death ◽  
Mitochondrial Signaling ◽  
Targeting Delivery ◽  
Potential Strategy ◽  
Triphenylphosphonium Bromide ◽  
Mitochondria Targeting

Mitochondria are membrane-enclosed organelles present in most eukaryotic cells, described as “power houses of the cell”. The mitochondria can be a target for inducing cancer cell death and for developing strategies to bypass multi drug resistance (MDR) mechanisms. 4-Carboxybutyl triphenylphosphonium bromide-polyethylene glycol-distearoylphosphatidylethanolamine (TPP-DSPE-PEG) and dequalinium-polyethylene glycol-distearoylphosphatidylethanolamine (DQA-DSPE-PEG) were synthesized as mitochondriotropic molecules. Mitochondria-targeting liposomes carrying resveratrol were constructed by modifying the liposome’s surface with TPP-PEG or DQA-PEG, resulting in TLS (Res) and DLS (Res), respectively, with the aim to obtain longer blood circulation and enhanced permeability and retention (EPR). Both TLS (Res) and DLS (Res) showed dimensions of approximately 120 nm and a slightly positive zeta potential. The enhanced cellular uptake and selective accumulation of TLS (Res) and DLS (Res) into the mitochondria were demonstrated by behavioral observation of rhodamine-labeled TLS or DLS, using confocal microscopy, and by resveratrol quantification in the intracellular organelle, using LC–MS/MS. Furthermore, TLS (Res) and DLS (Res) induced cytotoxicity of cancer cells by generating reactive oxygen species (ROS) and by dissipating the mitochondrial membrane potential. Our results demonstrated that TLS (Res) and DLS (Res) could provide a potential strategy to treat cancers by mitochondrial targeting delivery of therapeutics and stimulation of the mitochondrial signaling pathway.

scholarly journals Synthesis, Colloidal Characterization and Targetability of Phenylboronic Acid Functionalized α-Tocopheryl Polyethylene Glycol Succinate in Cancer Cells

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2258 ◽  
Author(s):  
Sanjay Tiwari ◽  
Jayant Sarolia ◽  
Vrushti Kansara ◽  
Nishith A. Chudasama ◽  
Kamalesh Prasad ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Cancer Cells ◽  
Cellular Localization ◽  
Phenylboronic Acid ◽  
Glycol Succinate ◽  
Drug Molecules ◽  
Spherical Core ◽  
Potential Strategy ◽  
Average Size ◽  
20 Nm

This study reports targetable micelles developed after covalent functionalization of α-tocopheryl polyethylene glycol succinate (TPGS) with amino phenylboronic acid (APBA). Nuclear magnetic resonance (NMR) and infrared (IR) spectroscopic results showed successful attachment of APBA to the hydrophilic segment of TPGS. Dynamic light scattering and small-angle neutron scattering studies revealed that the conjugate self-assembled in water to produce spherical core-shell micelles (14–20 nm) which remained stable against temperature (ca. 25–45 °C) and pH changes. The micelles could solubilize a high payload of paclitaxel (PLX) without exhibiting changes in the average size. However, at the saturation solubility, drug molecules migrated from the core to the shell region and engaged with APBA groups via π–π stacking interaction. Confocal microscopy and cell sorting analyses verified the effective translocation ability of TPGS-APBA micelles in sialic acid (SA) expressing MDA-MB-453 cells. At equivalent PLX dose, TPGS-APBA micelles showed about a twofold improvement in apoptotic death among the cells exposed for 2 h. Our findings indicate that the attachment of APBA can be a potential strategy for improving the intra-cellular localization of carriers among cancer cells expressing SA residues.

Preparation and characterization of glycosylated protein nanoparticles for astaxanthin mitochondria targeting delivery

2021 ◽  
Author(s):  
Yannan Chen ◽  
Shanshan Tie ◽  
Xuedi Zhang ◽  
Lijuan Zhang ◽  
Mingqian Tan
Keyword(s):  
Whey Protein ◽  
Self Assembly ◽  
Whey Protein Isolate ◽  
Protein Isolate ◽  
Assembly Method ◽  
Protein Nanoparticles ◽  
Targeting Delivery ◽  
Triphenylphosphonium Bromide ◽  
Mitochondria Targeting

Novel mitochondria targeting nanocarriers were prepared using triphenylphosphonium bromide (TPP) modified whey protein isolate (WPI)-dextran (DX) conjugates by self-assembly method for astaxanthin mitochondria targeting delivery. The nanocarriers of astaxanthin loaded...

scholarly journals Lead optimization of novel quinolone chalcone compounds by a structure-activity relationship (SAR) study to increase efficacy and metabolic stability

2021 ◽  
Author(s):  
James Knockleby ◽  
Aicha Djigo ◽  
I. Kalhari Lindamulage ◽  
Chandrabose Karthikeyan ◽  
Piyush Trivedi ◽  
...  
Keyword(s):  
Binding Site ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Cancer Drug ◽  
Multi Drug Resistance ◽  
Cancer Cell Death ◽  
Colchicine Binding Site ◽  
Structure Activity

Abstract Many agents targeting the colchicine binding site in tubulin have been developed as potential anticancer agents. However, none has successfully made it to the clinic, due mainly to dose limiting toxicities and the emergence of multi-drug resistance. Chalcones targeting tubulin have been proposed as a safe and effective alternative. To identify the most effective anticancer chalcone compound, we synthesized 17 quinolone-chalcone derivatives based on our previously published CTR-17 and CTR-20, and then carried out a structure-activity relationship study. We identified two compounds, CTR-21 [((E)-8-Methoxy-3-(3-(2-methoxyphenyl)-3-oxoprop-1-enyl) quinolin-2(1H)-one)] and CTR-32 [((E)-3-(3-(2-ethoxyphenyl)-3-oxoprop-1-enyl) quinolin-2(1H)-one)] as potential leads, which contain independent moieties that play a significant role in their enhanced activities. At the nM range, CTR-21 and CTR-32 effectively kill a panel of different cancer cells originated from a variety of different tissues including breast and skin. Both compounds also effectively kill multi-drug resistant cancer cells. Most importantly, CTR-21 and CTR-32 show a very high degree of selectivity against cancer cells. In silico, both of them dock near the colchicine-binding site with similar energies. However, only CTR-21 effectively prevents tubulin polymerization, leading to the cell cycle arrest at G2/M and, eventually, cancer cell death by apoptosis. Perhaps not surprisingly, the combination of CTR-21 and ABT-737, a Bcl-2 inhibitor, showed synergistic effect in killing cancer cells, since we previously found the “parental” CTR-20 also exhibited synergism. Taken together, CTR-21 can potentially be a highly effective and relatively safe anti-cancer drug.

Novel Mitochondria-targeted Drugs for Cancer Therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Jindriska Leischner Fialova ◽  
Martina Raudenska ◽  
Milan Jakubek ◽  
Zdenek Kejik ◽  
Pavel Martasek ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Special Focus ◽  
Targeted Drugs ◽  
Cancer Cell Death ◽  
Rational Development ◽  
Cancer Pharmacology ◽  
Mitochondrial Signaling ◽  
Promising Area

: The search for mitochondria-targeted drugs has dramatically risen over the last decade. Mitochondria are essential organelles serving not only as a powerhouse of the cell but also as a key player in cell proliferation and cell death. Their central role in the energetic metabolism, calcium homeostasis and apoptosis makes them an intriguing field of interest for cancer pharmacology. In cancer cells, many mitochondrial signaling and metabolic pathways are altered. These changes contribute to cancer development and progression. Due to changes in the mitochondrial metabolism and changes in a membrane potential, cancer cells are more susceptible to mitochondria-targeted therapy and the loss of functional mitochondria leads to arrest of cancer progression and/or a cancer cell death. Identification of mitochondrial changes specific for tumor growth and progression, a rational development of new mitochondria-targeted drugs and research on delivery agents led to the advance of this promising area. This review will highlight the current findings in mitochondrial biology which are important for cancer initiation, progression and resistance and discuss approaches of cancer pharmacology with a special focus to the anti-cancer drugs referred to as ‘mitocans’.

Strategies to Overcome Multi-Drug Resistance in Cancer Cells: the Contribution of siRNA and Nanotechnologies

2016 ◽  
Vol 20 (28) ◽  
pp. 2971-2982
Author(s):  
Cristina Mambet ◽  
Mihaela Chivu-Economescu ◽  
Lilia Matei ◽  
Mihai Stoian ◽  
Coralia Bleotu
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Multi Drug Resistance

Herbal Mixture Adsorbed to Polyethylene Glycol Microspheres Induces Apoptotic Effects on Breast Cancer Cells

2018 ◽  
Vol 15 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Aliny Aparecida Lopes Ribeiro ◽  
Fabiana Helen da Silva ◽  
Aron Carlos de Melo Cotrim ◽  
Alessandra Lima Deluque ◽  
Patricia Gelli Feres de Marchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Polyethylene Glycol ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Herbal Mixture ◽  
Apoptotic Effects

Resveratrol as an Enhancer of Apoptosis in Cancer: A Mechanistic Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Shahram Taeb ◽  
Hamed Haghi-Aminjan ◽  
Shima Afrashi ◽  
Kave Moloudi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Fas Ligand ◽  
Inhibitory Effect ◽  
Mitochondrial Pathway ◽  
Multi Drug Resistance ◽  
Chemotherapy Drugs ◽  
Normal Tissues ◽  
Anti Cancer

: Resistance of cancer cells to therapy is a challenge for achieving an appropriate therapeutic outcome. Cancer (stem) cells possess several mechanisms for increasing their survival following exposure to toxic agents such as chemotherapy drugs, radiation as well as immunotherapy. Evidences show that apoptosis plays a key role in response of cancer (stem) cells and their multi drug resistance. Modulation of both intrinsic and extrinsic pathways of apoptosis can increase efficiency of tumor response and amplify the therapeutic effect of radiotherapy, chemotherapy, targeted therapy and also immunotherapy. To date, several agents as adjuvant have been proposed to overcome resistance of cancer cells to apoptosis. Natural products are interesting because of low toxicity on normal tissues. Resveratrol is a natural herbal agent that has shown interesting anti-cancer properties. It has been shown to kill cancer cells selectively, while protecting normal cells. Resveratrol can augment reduction/oxidation (redox) reactions, thus increases the production of ceramide and the expression of apoptosis receptors such as Fas ligand (FasL). Resveratrol also triggers some pathways which induce mitochondrial pathway of apoptosis. On the other hand, resveratrol has an inhibitory effect on anti-apoptotic mediators such as nuclear factor κ B (NFκB), cyclooxygenase-2 (COX-2), phosphatidylinositol 3–kinase (PI3K) and mTOR. In this review, we explain the modulatory effects of resveratrol on apoptosis, which can augment the therapeutic efficiency of anti-cancer drugs or radiotherapy.

Co-delivery of Doxorubicin and D-α-Tocopherol Polyethylene Glycol 1000 Succinate by Magnetic Nanoparticles

2018 ◽  
Vol 18 (8) ◽  
pp. 1138-1147 ◽  
Author(s):  
Esra Metin ◽  
Pelin Mutlu ◽  
Ufuk Gündüz
Keyword(s):  
Breast Cancer ◽  
Polyethylene Glycol ◽  
Magnetic Nanoparticles ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Drug Loading ◽  
Gravimetric Analysis ◽  
Polyethylene Glycol 1000 ◽  
Mcf 7

Background: Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks. Objective: The aim of this study was targeted co-delivery of doxorubicin (Dox) which is an anticancer agent and D-α-Tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) to breast cancer cells. For this purpose, Magnetic Nanoparticles (MNPs) were synthesized and coated with Oleic Acid (OA). Coated nanoparticles were encapsulated in Poly Lactic-co-Glycolic Acid (PLGA) and TPGS polymers and loaded with Dox. The Nanoparticles (NPs) were characterized by Fourier Transform Infrared (FTIR) spectroscopy, zetapotential analysis, Dynamic Light Scattering (DLS) analysis, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscope (SEM) analysis. Results: The results showed that NPs were spherical, superparamagnetic and in the desired range for use in drug targeting. The targetability of NPs was confirmed. Moreover, TPGS and Dox loading was shown by TGA and FTIR analyses. NPs were internalized by cells and the cytotoxic effect of drug loaded NPs on sensitive (MCF-7) and drug-resistant (MCF-7/Dox) cells were examined. It was seen that the presence of TPGS increased cytotoxicity significantly. TPGS also enhanced drug loading efficiency, release rate, cellular internalization. In MCF- 7/Dox cells, the drug resistance seems to be decreased when Dox is loaded onto TPGS containing NPs. Conclusion: This magnetic PLGA nanoparticle system is important for new generation targeted chemotherapy and could be used for breast cancer treatment after in vivo tests.

scholarly journals A nanoselenium-coating biomimetic cytomembrane nanoplatform for mitochondrial targeted chemotherapy- and chemodynamic therapy through manganese and doxorubicin codelivery

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jianmin Xiao ◽  
Miao Yan ◽  
Ke Zhou ◽  
Hui Chen ◽  
Zhaowei Xu ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cancer Cells ◽  
High Yield ◽  
Ros Generation ◽  
Superoxide Dismutase 1 ◽  
Nuclear Targeting ◽  
Dual Mode ◽  
Red Cell Membrane ◽  
Cancer Cell Death ◽  
Drug Nanocarriers

Abstract The cell membrane is widely considered as a promising delivery nanocarrier due to its excellent properties. In this study, self-assembled Pseudomonas geniculate cell membranes were prepared with high yield as drug nanocarriers, and named BMMPs. BMMPs showed excellent biosafety, and could be more efficiently internalized by cancer cells than traditional red cell membrane nanocarriers, indicating that BMMPs could deliver more drug into cancer cells. Subsequently, the BMMPs were coated with nanoselenium (Se), and subsequently loaded with Mn2+ ions and doxorubicin (DOX) to fabricate a functional nanoplatform (BMMP-Mn2+/Se/DOX). Notably, in this nanoplatform, Se nanoparticles activated superoxide dismutase-1 (SOD-1) expression and subsequently up-regulated downstream H2O2 levels. Next, the released Mn2+ ions catalyzed H2O2 to highly toxic hydroxyl radicals (·OH), inducing mitochondrial damage. In addition, the BMMP-Mn2+/Se nanoplatform inhibited glutathione peroxidase 4 (GPX4) expression and further accelerated intracellular reactive oxygen species (ROS) generation. Notably, the BMMP-Mn2+/Se/DOX nanoplatform exhibited increased effectiveness in inducing cancer cell death through mitochondrial and nuclear targeting dual-mode therapeutic pathways and showed negligible toxicity to normal organs. Therefore, this nanoplatform may represent a promising drug delivery system for achieving a safe, effective, and accurate cancer therapeutic plan.

Sign in / Sign up

Export Citation Format

Share Document