A lysosome specific theranostic NO donor inhibits cancer cells by stimuli responsive molecular self-decomposition with an on-demand fluorescence pattern

The Analyst ◽  
2019 ◽  
Vol 144 (22) ◽  
pp. 6681-6688 ◽  
Author(s):  
Wuyang Hua ◽  
Jian Zhao ◽  
Xinyi Wang ◽  
Sinan Pei ◽  
Shaohua Gou
Keyword(s):  
Cancer Cells ◽  
Light Irradiation ◽  
Stimuli Responsive ◽  
No Donor ◽  
Apoptosis Pathway ◽  
Fluorescence Pattern ◽  
On Demand ◽  
No Releases

Mo-Nap-NO releases NO into lysosomes and activates an endogenous apoptosis pathway after being triggered by 460 nm light irradiation.

Carborane Guests for Cucurbit[7]uril Facilitate Strong Binding and on Demand Removal

2020 ◽  
Author(s):  
Anna Kataki-Anastasakou ◽  
Jonathan C. Axtell ◽  
Selena Hernandez ◽  
RafalM. Dziedzic ◽  
Gary J. Balaich ◽  
...  
Keyword(s):  
Free State ◽  
Stimuli Responsive ◽  
Additional Consideration ◽  
Boron Clusters ◽  
High Affinity ◽  
On Demand ◽  
Azide Anion ◽  
Strong Binding

High affinity guest have been reported for the macrocyclic host cucurbit[7]uril (CB[7]), enabling widespread applications, but preventing CB[7] materials from being returned to their guest-free state for reuse. Here we present polyhedral boron clusters (carboranes) as strongly-binding, yet easily removable, guests for CB[7]. Aided by a Pd-catalyzed coupling of an azide anion, we prepared boron-functionalized 9<i>-</i>amino and 9-ammonium modified <i>ortho-</i>carboranes that bind to CB[7] with a <i>K<sub>a</sub></i>=10<sup>10</sup> M<sup>-1</sup>. Upon treatment with base, the <i>ortho</i>-carboranes<i> </i>readily undergo deboronation to yield anionic <i>nido</i>-carborane, a poor guest of CB[7], facilitating recovery of guest-free CB[7]. We showcase the utility of the modified <i>ortho</i>-carborane guest by recycling a CB[7]-functionalized resin. With this report, we introduce stimuli-responsive decomplexation as an additional consideration in the design of high affinity host-guest complexes.

scholarly journals Electrochemotherapy with Calcium Chloride and 17β-Estradiol Modulated Viability and Apoptosis Pathway in Human Ovarian Cancer

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 19
Author(s):  
Zofia Łapińska ◽  
Michał Dębiński ◽  
Anna Szewczyk ◽  
Anna Choromańska ◽  
Julita Kulbacka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Calcium Chloride ◽  
Morphological Changes ◽  
Cell Membrane Permeability ◽  
Immunocytochemical Staining ◽  
Ovarian Cancer Cells ◽  
Apoptosis Pathway ◽  
17Β Estradiol

Estrogens (Es) play a significant role in the carcinogenesis and progression of ovarian malignancies. Depending on the concentration, Es may have a protective or toxic effect on cells. Moreover, they can directly or indirectly affect the activity of membrane ion channels. In the presented study, we investigated in vitro the effectiveness of the ovarian cancer cells (MDAH-2774) pre-incubation with 17β-estradiol (E2; 10 µM) in the conventional chemotherapy (CT) and electrochemotherapy (ECT) with cisplatin or calcium chloride. We used three different protocols of electroporation including microseconds (µsEP) and nanoseconds (nsEP) range. The cytotoxic effect of the applied treatment was examined by the MTT assay. We used fluorescent staining and holotomographic imaging to observe morphological changes. The immunocytochemical staining evaluated the expression of the caspase-12. The electroporation process’s effectiveness was analyzed by a flow cytometer using the Yo-Pro™-1 dye absorption assay. We found that pre-incubation of ovarian cancer cells with 17β-estradiol may effectively enhance the chemo- and electrochemotherapy with cisplatin and calcium chloride. At the same time, estradiol reduced the effectiveness of electroporation, which may indicate that the mechanism of increasing the effectiveness of ECT by E2 is not related to the change of cell membrane permeability.

scholarly journals Glutathione peroxidase-1 regulates ASK1-dependent apoptosis via interaction with TRAF2 in RIPK3-negative cancer cells

2021 ◽  
Author(s):  
Sunmi Lee ◽  
Eun-Kyung Lee ◽  
Dong Hoon Kang ◽  
Jiyoung Lee ◽  
Soo Hyun Hong ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Cancer Cells ◽  
Mammalian Cells ◽  
Apoptosis Pathway ◽  
Glutathione Peroxidase 1 ◽  
Peroxidase Enzyme ◽  
Thioredoxin 1 ◽  
Sequential Activation ◽  
Induced Apoptosis

AbstractGlutathione peroxidase (GPx) is a selenocysteine-containing peroxidase enzyme that defends mammalian cells against oxidative stress, but the role of GPx signaling is poorly characterized. Here, we show that GPx type 1 (GPx1) plays a key regulatory role in the apoptosis signaling pathway. The absence of GPx1 augmented TNF-α-induced apoptosis in various RIPK3-negative cancer cells by markedly elevating the level of cytosolic H2O2, which is derived from mitochondria. At the molecular level, the absence of GPx1 led to the strengthened sequential activation of sustained JNK and caspase-8 expression. Two signaling mechanisms are involved in the GPx1-dependent regulation of the apoptosis pathway: (1) GPx1 regulates the level of cytosolic H2O2 that oxidizes the redox protein thioredoxin 1, blocking ASK1 activation, and (2) GPx1 interacts with TRAF2 and interferes with the formation of the active ASK1 complex. Inducible knockdown of GPx1 expression impaired the tumorigenic growth of MDA-MB-231 cells (>70% reduction, P = 0.0034) implanted in mice by promoting apoptosis in vivo. Overall, this study reveals the apoptosis-related signaling function of a GPx family enzyme highly conserved in aerobic organisms.

scholarly journals Ruthenium-based PACT agents based on bisquinoline chelates: synthesis, photochemistry, and cytotoxicity

2021 ◽  
Author(s):  
Anja Busemann ◽  
Ingrid Flaspohler ◽  
Xue-Quan Zhou ◽  
Claudia Schmidt ◽  
Sina K. Goetzfried ◽  
...  
Keyword(s):  
Quantum Yield ◽  
Singlet Oxygen ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Ruthenium Complex ◽  
Human Cancer ◽  
Light Irradiation ◽  
Quantum Yields ◽  
Light Activation ◽  
Human Cancer Cells

AbstractThe known ruthenium complex [Ru(tpy)(bpy)(Hmte)](PF6)2 ([1](PF6)2, where tpy = 2,2’:6’,2″-terpyridine, bpy = 2,2’-bipyridine, Hmte = 2-(methylthio)ethanol) is photosubstitutionally active but non-toxic to cancer cells even upon light irradiation. In this work, the two analogs complexes [Ru(tpy)(NN)(Hmte)](PF6)2, where NN = 3,3'-biisoquinoline (i-biq, [2](PF6)2) and di(isoquinolin-3-yl)amine (i-Hdiqa, [3](PF6)2), were synthesized and their photochemistry and phototoxicity evaluated to assess their suitability as photoactivated chemotherapy (PACT) agents. The increase of the aromatic surface of [2](PF6)2 and [3](PF6)2, compared to [1](PF6)2, leads to higher lipophilicity and higher cellular uptake for the former complexes. Such improved uptake is directly correlated to the cytotoxicity of these compounds in the dark: while [2](PF6)2 and [3](PF6)2 showed low EC50 values in human cancer cells, [1](PF6)2 is not cytotoxic due to poor cellular uptake. While stable in the dark, all complexes substituted the protecting thioether ligand upon light irradiation (520 nm), with the highest photosubstitution quantum yield found for [3](PF6)2 (Φ[3] = 0.070). Compounds [2](PF6)2 and [3](PF6)2 were found both more cytotoxic after light activation than in the dark, with a photo index of 4. Considering the very low singlet oxygen quantum yields of these compounds, and the lack of cytotoxicity of the photoreleased Hmte thioether ligand, it can be concluded that the toxicity observed after light activation is due to the photoreleased aqua complexes [Ru(tpy)(NN)(OH2)]2+, and thus that [2](PF6)2 and [3](PF6)2 are promising PACT candidates. Graphic abstract

A stimuli responsive liposome loaded hydrogel provides flexible on-demand release of therapeutic agents

2017 ◽  
Vol 48 ◽  
pp. 110-119 ◽  
Author(s):  
Hugh S. O’Neill ◽  
Caroline C. Herron ◽  
Conn L. Hastings ◽  
Roel Deckers ◽  
Adolfo Lopez Noriega ◽  
...  
Keyword(s):  
Therapeutic Agents ◽  
Stimuli Responsive ◽  
On Demand

scholarly journals Polymerisation-induced self-assembly (PISA) as a straightforward formulation strategy for stimuli-responsive drug delivery systems and biomaterials: recent advances

2021 ◽  
Vol 9 (1) ◽  
pp. 38-50
Author(s):  
Hien Phan ◽  
Vincenzo Taresco ◽  
Jacques Penelle ◽  
Benoit Couturaud
Keyword(s):  
Drug Delivery ◽  
Block Copolymers ◽  
Drug Release ◽  
Self Assembly ◽  
Drug Delivery Systems ◽  
Amphiphilic Block Copolymers ◽  
Stimuli Responsive ◽  
Site Specific ◽  
On Demand ◽  
Redox Agents

Stimuli-responsive amphiphilic block copolymers obtained by PISA have emerged as promising nanocarriers for enhancing site-specific and on-demand drug release in response to a range of stimuli such as pH, redox agents, light or temperature.

scholarly journals Controlled drug release to cancer cells from modular one-photon visible light-responsive micellar system

2016 ◽  
Vol 52 (69) ◽  
pp. 10525-10528 ◽  
Author(s):  
Saemi O. Poelma ◽  
Seung Soo Oh ◽  
Sameh Helmy ◽  
Abigail S. Knight ◽  
G. Leslie Burnett ◽  
...  
Keyword(s):  
Drug Release ◽  
Visible Light ◽  
Small Molecules ◽  
Cancer Cells ◽  
Controlled Drug Release ◽  
Micellar System ◽  
On Demand ◽  
System P

We present a one-photon visible light-responsive micellar system for efficient, on-demand delivery of small molecules.

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