scholarly journals Mitochondria targeting molecular transporters: synthesis, lipophilic effect, and ionic complex

Drug Delivery ◽  
2022 ◽  
Vol 29 (1) ◽  
pp. 270-283
Author(s):  
Akula S. N. Murthy ◽  
Sanket Das ◽  
Tejinder Singh ◽  
Tae-Wan Kim ◽  
Nasim Sepay ◽  
...  
Keyword(s):  
Ionic Complex ◽  
Molecular Transporters ◽  
Mitochondria Targeting

scholarly journals Maturation of Mitochondrially Targeted Prx V Involves a Second Cleavage by Mitochondrial Intermediate Peptidase That Is Sensitive to Inhibition by H2O2

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 346
Author(s):  
Juhyun Sim ◽  
Jiyoung Park ◽  
Hyun Ae Woo ◽  
Sue Goo Rhee
Keyword(s):  
Short Form ◽  
Mitochondrial Matrix ◽  
Mitochondrial Processing Peptidase ◽  
Mouse Tissues ◽  
N Terminus ◽  
Mitochondrial Intermediate Peptidase ◽  
Subsequent Degradation ◽  
Processing Peptidase ◽  
Mitochondria Targeting ◽  
Over Time

Prx V mRNA contains two in-frame AUG codons, producing a long (L-Prx V) and short form of Prx V (S-Prx V), and mouse L-Prx V is expressed as a precursor protein containing a 49-amino acid N-terminal mitochondria targeting sequence. Here, we show that the N-terminal 41-residue sequence of L-Prx V is cleaved by mitochondrial processing peptidase (MPP) in the mitochondrial matrix to produce an intermediate Prx V (I-Prx V) with a destabilizing phenylalanine at its N-terminus, and further, that the next 8-residue sequence is cleaved by mitochondrial intermediate peptidase (MIP) to convert I-Prx V to a stabilized mature form that is identical to S-Prx V. Further, we show that when mitochondrial H2O2 levels are increased in HeLa cells using rotenone, in several mouse tissues by deleting Prx III, and in the adrenal gland by deleting Srx or by exposing mice to immobilized stress, I-Prx V accumulates transiently and mature S-Prx V levels decrease in mitochondria over time. These findings support the view that MIP is inhibited by H2O2, resulting in the accumulation and subsequent degradation of I-Prx V, identifying a role for redox mediated regulation of Prx V proteolytic maturation and expression in mitochondria.

scholarly journals Multi-Walled Carbon Nanotubes Decorated with Guanidinylated Dendritic Molecular Transporters: An Efficient Platform for the Selective Anticancer Activity of Doxorubicin

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 858
Author(s):  
Kyriaki-Marina Lyra ◽  
Archontia Kaminari ◽  
Katerina N. Panagiotaki ◽  
Konstantinos Spyrou ◽  
Sergios Papageorgiou ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Delivery System ◽  
Colloidal Stability ◽  
Triggered Release ◽  
Selective Toxicity ◽  
Molecular Transporters ◽  
Multi Walled Carbon Nanotubes ◽  
Walled Carbon Nanotubes

An efficient doxorubicin (DOX) drug delivery system with specificity against tumor cells was developed, based on multi-walled carbon nanotubes (MWCNTs) functionalized with guanidinylated dendritic molecular transporters. Acid-treated MWCNTs (oxCNTs) interacted both electrostatically and through hydrogen bonding and van der Waals attraction forces with guanidinylated derivatives of 5000 and 25,000 Da molecular weight hyperbranched polyethyleneimine (GPEI5K and GPEI25K). Chemical characterization of these GPEI-functionalized oxCNTs revealed successful decoration with GPEIs all over the oxCNTs sidewalls, which, due to the presence of guanidinium groups, gave them aqueous compatibility and, thus, exceptional colloidal stability. These GPEI-functionalized CNTs were subsequently loaded with DOX for selective anticancer activity, yielding systems of high DOX loading, up to 99.5% encapsulation efficiency, while the DOX-loaded systems exhibited pH-triggered release and higher therapeutic efficacy compared to that of free DOX. Most importantly, the oxCNTs@GPEI5K-DOX system caused high and selective toxicity against cancer cells in a non-apoptotic, fast and catastrophic manner that cancer cells cannot recover from. Therefore, the oxCNTs@GPEI5K nanocarrier was found to be a potent and efficient nanoscale DOX delivery system, exhibiting high selectivity against cancerous cells, thus constituting a promising candidate for cancer therapy.

scholarly journals pH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
He Wang ◽  
Wenwen Shi ◽  
Danning Zeng ◽  
Qiudi Huang ◽  
Jiacui Xie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Disulfide Bonds ◽  
Cancer Metastasis ◽  
Mitochondrial Outer Membrane ◽  
Drug Resistant ◽  
Redox Responsive ◽  
Dimethylmaleic Anhydride ◽  
Extended Circulation ◽  
Mitochondria Targeting

Abstract Background Mitochondria play a role in the occurrence, development, drug resistance, metastasis, and other functions of cancer and thus are a drug target. An acid-activated mitochondria-targeting drug nanocarrier with redox-responsive function was constructed in the present study. However, whether this vector can precisely delivery paclitaxel (PTX) to enhance therapeutic efficacy in drug-resistant lung cancer is unknown. Results Acid-cleavable dimethylmaleic anhydride (DA) was used to modify pluronic P85-conjugated mitochondria-targeting triphenylphosphonium (TPP) using disulfide bonds as intermediate linkers (DA-P85-SS-TPP and DA-P-SS-T). The constructed nanocarriers demonstrated enhanced cellular uptake and selective mitochondrial targeting at extracellular pH characteristic for a tumor (6.5) and were characterized by extended circulation in the blood. TPP promoted the targeting of the DA-P-SS-T/PTX nanomicelles to the mitochondrial outer membrane to decrease the membrane potential and ATP level, resulting in inhibition of P-glycoprotein and suppression of drug resistance and cancer metastasis. PTX was also rapidly released in the presence of high glutathione (GSH) levels and directly diffused into the mitochondria, resulting in apoptosis of drug-resistant lung cancer cells. Conclusions These promising results indicated that acid-activated mitochondria-targeting and redox-responsive nanomicelles potentially represent a significant advancement in cancer treatment. Graphic Abstarct

scholarly journals Synthetic Mitochondria-Targeting Peptides Incorporating α-Aminoisobutyric Acid with a Stable Amphiphilic Helix Conformation in Plant Cells

2021 ◽  
Vol 7 (4) ◽  
pp. 1475-1484
Author(s):  
Kayo Terada ◽  
Joan Gimenez-Dejoz ◽  
Taichi Kurita ◽  
Kazusato Oikawa ◽  
Hirotaka Uji ◽  
...  
Keyword(s):  
Plant Cells ◽  
Aminoisobutyric Acid ◽  
Amphiphilic Helix ◽  
Helix Conformation ◽  
Mitochondria Targeting

Mitochondria-targeting fluorescent sensor for on-off-on response to Cu2+ and ATP in cells and zebrafish

The Analyst ◽  
2021 ◽  
Author(s):  
Wan Sun ◽  
Guofeng Liu ◽  
Mingqiong Tong ◽  
Haozhan Wang ◽  
Shuhan Liu
Keyword(s):  
Adenosine Triphosphate ◽  
Fluorescent Sensor ◽  
Biological Processes ◽  
Fluorescent Molecule ◽  
Cupric Ion ◽  
Mitochondria Targeting ◽  
In Cells

Cupric ion (Cu2+) and adenosine triphosphate (ATP) are functionally important in mitochondria and play essential roles in many important biological processes. In this work, a mitochondria-targeting fluorescent molecule Mito-A was...

A smart mitochondria-targeting TP-NIR fluorescent probe for selective and sensitive sensing H2S in living cells and mice

2021 ◽  
Author(s):  
Qiaomei Yang ◽  
Liyi Zhou ◽  
Longpeng Peng ◽  
Gangqiang Yuan ◽  
Haiyuan Ding ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Fluorescent Probe ◽  
Near Infrared ◽  
Living Cells ◽  
Signal Molecules ◽  
Two Photon ◽  
Mitochondria Targeting

Hydrogen sulfide (H2S) is one of the important gaseous signal molecules and plays key roles in various biologically crucial processes. In this work, we report a novel two-photon near-infrared (TP-NIR)...

scholarly journals Guanidinoneomycin-Maleimide Molecular Transporter: Synthesis, Chemistry and Cellular Uptake

2021 ◽  
Author(s):  
Alessandro Volonterio ◽  
Kaivin Hadidi ◽  
Maria Cristina Bellucci ◽  
Sergio Dall'Angelo ◽  
Alasdair Leeson-Payne ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Cellular Uptake ◽  
Molecular Transporters

Guanidinoglycosides are a class of non-cytotoxic molecular transporters capable of delivering high molecular weight bioactive cargos into cells at low nanomolar concentrations. Efficient bioconjugation with guanidinoglycosides has been previously demonstrated...

Sign in / Sign up

Export Citation Format

Share Document