The Potential Role of Cell Penetrating Peptides in the Intracellular Delivery of Proteins for Therapy of Erythroid Related Disorders

Papadopoulou, Lefkothea C.; Tsiftsoglou, Asterios S.

doi:10.3390/ph6010032

Cited by 16 publications

(8 citation statements)

References 134 publications

(167 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As most CPPs cross cell membrane without selectivity, conjugation of CPPs to type II peptides leads to nonspecific binding to cells in the circulatory system, leading to further reduction of half-life and increase of off-target effects. [7] On the other hand, type III peptides are highly toxic. Translation of peptides in this group has been unsuccessful.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Activatable Protein Nanoparticles for Targeted Delivery of Therapeutic Peptides

Gou

et al. 2018

Advanced Materials

View full text Add to dashboard Cite

Clinical translation of therapeutic peptides, particularly those that require penetration of the cell membrane or are cytolytic, is a major challenge. A novel approach based on a complementary mechanism, which has been widely used for guided synthesis of DNA or RNA nanoparticles, for de novo design of activatable protein nanoparticles (APNPs) for targeted delivery of therapeutic peptides is described. APNPs are formed through self-assembly of three independent polypeptides based on pairwise coiled-coil dimerization. They are capable of long circulation in the blood and can be engineered to target diseases. Peptides to be delivered are incorporated into APNPs and released into the disease microenvironment by locally enriched proteases. It is demonstrated that APNPs mediate efficient delivery of NR2B9c, a neuroprotective peptide that functions after cell penetration, and melittin, a cytolytic peptide that perturbs the lipid bilayer, for effective treatment of stroke and cancer, respectively. Due to their robust properties, simple design, and economic costs, APNPs have great potential to serve as a versatile platform for controlled delivery of therapeutic peptides.

show abstract

mentioning

confidence: 99%

“…TAT-based CPP penetrates most biological membranes without selectivity and thus nonspecifically binds to cells or organs during circulation. [7] It is possible that intravenous administration of Tat-NR2B9c in human patients does not allow the delivery of a pharmacologically significant amount of peptide to the brain.…”

mentioning

confidence: 99%

Activatable Protein Nanoparticles for Targeted Delivery of Therapeutic Peptides

Gou

et al. 2018

Advanced Materials

View full text Add to dashboard Cite

show abstract

“…Recently, many researchers have discussed the potential role of CPPs in the intracellular delivery and confirmed their efficiency in vitro and in vivo 47. Especially, HIV TAT protein transduction domain was prominent in delivering efficiency in human and mouse haematopoietic cells38484950.…”

Section: Discussionmentioning

confidence: 96%

Thioredoxin-interacting protein regulates haematopoietic stem cell ageing and rejuvenation by inhibiting p38 kinase activity

et al. 2016

View full text Add to dashboard Cite

Ageing is a natural process in living organisms throughout their lifetime, and most elderly people suffer from ageing-associated diseases. One suggested way to tackle such diseases is to rejuvenate stem cells, which also undergo ageing. Here we report that the thioredoxin-interacting protein (TXNIP)-p38 mitogen-activated protein kinase (p38) axis regulates the ageing of haematopoietic stem cells (HSCs), by causing a higher frequency of long-term HSCs, lineage skewing, a decrease in engraftment, an increase in reactive oxygen species and loss of Cdc42 polarity. TXNIP inhibits p38 activity via direct interaction in HSCs. Furthermore, cell-penetrating peptide (CPP)-conjugated peptide derived from the TXNIP-p38 interaction motif inhibits p38 activity via this docking interaction. This peptide dramatically rejuvenates aged HSCs in vitro and in vivo. Our findings suggest that the TXNIP-p38 axis acts as a regulatory mechanism in HSC ageing and indicate the potent therapeutic potential of using CPP-conjugated peptide to rejuvenate aged HSCs.

show abstract

“…However, there are still several obstacles such as lack of specificity for the target, immunogenicity, cytotoxicity, and instability [21]. In addition, most CPPs require high treatment concentrations for cell permeation even in an in vitro environment [22].…”

Section: Introductionmentioning

confidence: 99%

Cell-Penetrating Peptides Enhance the Activity of Human Fibroblast Growth Factor 2 by Prolonging the Retention Time: A New Vision for Drug-Delivery Systems

Lee¹,

Kwon

et al. 2020

IJMS

View full text Add to dashboard Cite

Cell-penetrating peptides (CPPs) are defined by their ability to deliver cargo into cells and have been studied and developed as a promising drug-delivery system (DDS). However, the issue of whether the CPPs that have already entered the cells can be re-released or reused has not been studied. The purpose of this research was to construct CPP-conjugated human fibroblast growth factor 2 (hFGF2) and investigate whether they can be re-released from the cell membrane for reuse. This study combined hFGF2 with Tat or Ara27, a newly developed CPP derived from the zinc knuckle (CCHC-type) family protein of Arabidopsis. Human dermal fibroblast (HDF) was treated with Tat-conjugated hFGF2 (tFGF2) and Ara27-conjugated hFGF2 (NR-FGF2) for both long and short durations, and the effects on cell growth were compared. Furthermore, tFGF2 and NR-FGF2 re-released from the cells were quantified and the effects were evaluated by culturing HDF in a conditioned medium. Interestingly, the proliferation of HDF increased only when NR-FGF2 was treated for 1 h in endocytosis-independent manner. After 1 h, NR-FGF2 was significantly re-released, reaching a maximum concentration at 5 h. Furthermore, increased proliferation of HDF cultured in the conditioned medium containing re-released NR-FGF2 was discovered. While previous studies have focused on the delivery of cargo and its associated applications, this study has revealed that combinations of superior CPPs and therapeutics can be expected to prolong both the retention time and the cell-penetrating capacity, even in the presence of external factors. Therefore, CPPs can be applied in the context of topical drugs and cosmetics as a new DDS approach.

show abstract

The Potential Role of Cell Penetrating Peptides in the Intracellular Delivery of Proteins for Therapy of Erythroid Related Disorders

Cited by 16 publications

References 134 publications

Activatable Protein Nanoparticles for Targeted Delivery of Therapeutic Peptides

Activatable Protein Nanoparticles for Targeted Delivery of Therapeutic Peptides

Thioredoxin-interacting protein regulates haematopoietic stem cell ageing and rejuvenation by inhibiting p38 kinase activity

Cell-Penetrating Peptides Enhance the Activity of Human Fibroblast Growth Factor 2 by Prolonging the Retention Time: A New Vision for Drug-Delivery Systems

Contact Info

Product

Resources

About