Transporter-Mediated Drug Delivery

Gyimesi, Gergely; Hediger, Matthias A.

doi:10.3390/molecules28031151

Cited by 16 publications

(9 citation statements)

References 524 publications

(644 reference statements)

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“…On the other hand, our GO term analysis also clearly demonstrated significant downregulation of transmembrane transporter coding RNAs in vimentin‐positive IBC‐NSTs; SLC transporter plays a very important role in the uptake of chemotherapeutic agents into carcinoma cells 56–60 . The KEGG pathway analysis also clearly demonstrated ABC transporter coding RNAs being significantly upregulated in vimentin‐positive IBC‐NSTs, and these transporters are known to play very important roles in the efflux chemotherapeutic agents from carcinoma cells 56–60 .…”

Section: Discussionmentioning

confidence: 61%

“…[52][53][54][55] On the other hand, our GO term analysis also clearly demonstrated significant downregulation of transmembrane transporter coding RNAs in vimentinpositive IBC-NSTs; SLC transporter plays a very important role in the uptake of chemotherapeutic agents into carcinoma cells. [56][57][58][59][60] The KEGG pathway analysis also clearly demonstrated ABC transporter coding RNAs being significantly upregulated in vimentin-positive IBC-NSTs, and these transporters are known to play very important roles in the efflux chemotherapeutic agents from carcinoma cells. [56][57][58][59][60] Since transmembrane transport coding RNAs regulate drug absorption and excretion in cancer cells, the pharmacodynamic activity in vimentin-positive IBC-NSTs may be lower than that in vimentin-negative IBC-NSTs, so that they may have a greater propensity to develop drug resistance to anticancer agents than vimentin-negative IBC-NSTs, which could also contribute to the heightened malignant potential of vimentinpositive IBC-NSTs.…”

Section: Mitotic Cytokinesismentioning

confidence: 93%

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Vimentin‐positive invasive breast carcinoma of no special type: A breast carcinoma with lethal biological characteristics

Ichinose,

Hasebe,

Hirasaki

et al. 2023

Pathology International

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Vimentin is a stable mesenchymal immunohistochemical marker and is widely recognized as a major marker of mesenchymal tumors. The purpose of the present study was to investigate if the vimentin expression status might serve as a significant predictor of outcomes in patients with invasive breast carcinoma of no special type (IBC‐NST) and to investigate, by comprehensive RNA sequencing analyses, the mechanisms involved in the heightened malignant potential of vimentin‐positive IBC‐NSTs. This study, conducted using the data of 855 patients with IBC‐NST, clearly identified vimentin expression status as a very important independent biological parameter for accurately predicting the outcomes in patients with IBC‐NST. RNA sequence analyses clearly demonstrated significant upregulation of coding RNAs known to be closely associated with cell proliferation or cellular senescence, and significant downregulation of coding RNAs known to be closely associated with transmembrane transport in vimentin‐positive IBC‐NSTs. We conclude that vimentin‐positive IBC‐NSTs show heightened malignant biological characteristics, possibly attributable to the upregulation of RNAs closely associated with proliferative activity and cellular senescence, and downregulation of RNAs closely associated with transmembrane transport in IBC‐NSTs.

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Section: Discussionmentioning

confidence: 61%

Section: Mitotic Cytokinesismentioning

confidence: 93%

Vimentin‐positive invasive breast carcinoma of no special type: A breast carcinoma with lethal biological characteristics

Ichinose,

Hasebe,

Hirasaki

et al. 2023

Pathology International

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“…Brent & Fawcett 69 reported the unexpected nding that in E8.5 embryos or younger rat embryos up to 95% of the amino acids in tissues of the embryo were derived from metabolism of maternal proteins. Later in development placental transfer of amino acids is a prominent feature of placental function in both human and rodents 36,37,42,43 .…”

Section: Discussionmentioning

confidence: 99%

Effects of paracetamol (acetaminophen) on the expression of solute carriers (SLCs) in late gestation fetal rat brain, choroid plexus and the placenta

Huang

Qiu

Dziegielewska

et al. 2023

Preprint

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Solute carriers (SLCs) regulate transfer of a wide range of molecules across cell membranes using facilitative or secondary active transport. In pregnancy, these transporters, expressed at the placental barrier, are important for delivery of nutrients to the developing fetus, whilst also limiting entry of potentially harmful substances such as drugs. In the present study, RNA-sequencing analysis was used to investigate expression of SLCs in the fetal (E19) rat brain, choroid plexus and placenta in untreated controls and following maternal paracetamol treatment. In the treated group, paracetamol (15 mg/kg) was administered to dams twice daily for 5 days (from E15 to E19). Expression of several SLCs was significantly different in paracetamol treatment group compared to controls in all tissues tested, with ion, amino acid, neurotransmitter and sugar transporters most affected. The number of SLC transcripts that changed significantly following treatment was the highest in the choroid plexus and lowest in the brain. In control tissues, overall expression of SLCs was highest in the placenta. However, following paracetamol treatment, SLC transcripts in the placenta were either unchanged or significantly lower. Together, these results suggest that administration of paracetamol during pregnancy could potentially disrupt fetal nutrient homeostasis and affect brain development.

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“…Moreover, glucose-/galactose-based nanoconjugate formulation enhances the delivery of anti-BACE1 siRNA and 3D6 antibody fragments (3D6-Fab) in the transgenic mouse model of Alzheimer's disease through the GLUT1-mediated uptake pathway. 118 Nanoconjugation provides a new direction in the field of protein aggregation. Therefore, nanoconjugation could provide highly efficient therapeutic strategies for protein misfolding diseases.…”

Section: Potential Nano-osmolyte Aggregation Inhibitorsmentioning

confidence: 99%

“…However, amino acids conjugated with liposomes containing drugs interact more effectively with the solute carrier (SLC) proteins to deliver the drugs into the carcinoma cell lines. Moreover, glucose-/galactose-based nanoconjugate formulation enhances the delivery of anti-BACE1 siRNA and 3D6 antibody fragments (3D6-Fab) in the transgenic mouse model of Alzheimer’s disease through the GLUT1-mediated uptake pathway …”

Section: Potential Nano-osmolyte Aggregation Inhibitorsmentioning

confidence: 99%

Nano-Osmolyte Conjugation: Tailoring the Osmolyte-Protein Interactions at the Nanoscale

Sharma,

Dar,

Wijayasinghe

et al. 2023

ACS Omega

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Osmolytes are small organic compounds accumulated at higher concentrations in the cell under various stress conditions like high temperature, high salt, high pressure, etc. Osmolytes mainly include four major classes of compounds including sugars, polyols, methylamines, and amino acids and their derivatives. In addition to their ability to maintain protein stability and folding, these osmolytes, also termed as chemical chaperones, can prevent protein misfolding and aggregation. Although being efficient protein folders and stabilizers, these osmolytes exhibit certain unavoidable limitations such as nearly molar concentrations of osmolytes being required for their effect, which is quite difficult to achieve inside a cell or in the extracellular matrix due to nonspecificity and limited permeability of the blood–brain barrier system and reduced bioavailability. These limitations can be overcome to a certain extent by using smart delivery platforms for the targeted delivery of osmolytes to the site of action. In this context, osmolyte-functionalized nanoparticles, termed nano-osmolytes, enhance the protein stabilization and chaperone efficiency of osmolytes up to 105 times in certain cases. For example, sugars, polyols, and amino acid functionalized based nano-osmolytes have shown tremendous potential in preventing protein aggregation. The enhanced potential of nano-osmolytes can be attributed to their high specificity at low concentrations, high tunability, amphiphilicity, multivalent complex formation, and efficient drug delivery system. Keeping in view the promising potential of nano-osmolytes conjugation in tailoring the osmolyte–protein interactions, as compared to their molecular forms, the present review summarizes the recent advancements of the nano-osmolytes that enhance the protein stability/folding efficiency and ability to act as artificial chaperones with increased potential to prevent protein misfolding disorders. Some of the potential nano-osmolyte aggregation inhibitors have been highlighted for large-scale screening with future applications in aggregation disorders. The synthesis of nano-osmolytes by numerous approaches and future perspectives are also highlighted.

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Transporter-Mediated Drug Delivery

Cited by 16 publications

References 524 publications

Vimentin‐positive invasive breast carcinoma of no special type: A breast carcinoma with lethal biological characteristics

Vimentin‐positive invasive breast carcinoma of no special type: A breast carcinoma with lethal biological characteristics

Effects of paracetamol (acetaminophen) on the expression of solute carriers (SLCs) in late gestation fetal rat brain, choroid plexus and the placenta

Nano-Osmolyte Conjugation: Tailoring the Osmolyte-Protein Interactions at the Nanoscale

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