Cell-penetrating peptide CGKRK mediates efficient and widespread targeting of bladder mucosa following focal injury

Griffin, James I.; Cheng, Siu Kit Kevin; Hayashi, Tomoko; Carson, Dennis A.; Saraswathy, Manju; Nair, Devatha P.; Simberg, Dmitri

doi:10.1016/j.nano.2017.04.004

Cited by 21 publications

(7 citation statements)

References 24 publications

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“…Peptides, especially membrane-active cationic peptides capable of transducing the cell membrane, have been vastly studied as delivery vectors for intracellular cargo delivery. − Even though it can be touted as a simple and effective strategy, they are yet to be established as drug delivery vectors for clinical applications. This has been majorly due to the poor half-life in biological systems attributable to premature proteolytic cleavage in the presence of biological tissues.…”

Section: Discussionmentioning

confidence: 99%

Delivery of Small Molecules by Syndiotactic Peptides for Breast Cancer Therapy

et al. 2022

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The utilization of peptide-based drug delivery systems has been suboptimal due to their poor proteolytic susceptibility, poor cell permeability, and limited tumor homing capabilities. Earlier attempts in using d-enantiomers in peptide sequences increased proteolytic stability but have compromised the overall penetration capability. We designed a series of peptides (STRAPs) with a syndiotactic polypeptide backbone that can potentially form a spatial array of cationic groups, an important feature that facilitates cellular uptake. The peptides penetrate cell membranes through a combination of active and passive modes. Furthermore, the cellular uptake of the peptides was unaffected by the presence of or treatment with bovine serum and human plasma. The designed peptides successfully delivered methotrexate, an anticancer drug, to the in vitro and in vivo models of breast cancer, with the best performing peptide STRAP-4-MTX conjugate having an EC50 value of 1.34 μM. Peptide drug delivery in mouse xenograft models showed a greater reduction of primary tumor and metastasis of breast cancer, in comparison to methotrexate of the same dose. The in vivo biodistribution assay of the STRAP-4 peptide suggests that the peptide accumulates at the tumor site after 2 h of treatment, and in the absence of tumors, the peptide gets metabolized and excreted from the system.

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Section: Discussionmentioning

confidence: 99%

Delivery of Small Molecules by Syndiotactic Peptides for Breast Cancer Therapy

et al. 2022

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“…Griffin et al found the peptide CGKRK (Cys-Gly-Lys-Arg-Lys) could penetrate mucosal layers following focal mechanical damage to the urothelium [ 122 ]. After the focal injury, the intravesical peptide could bind to the entire urothelium, further penetrating the deeper tissues than the control without the injury treatment.…”

Section: Physical Methods To Get Drugs Across Bladder Penetrating mentioning

confidence: 99%

Strategies to Get Drugs across Bladder Penetrating Barriers for Improving Bladder Cancer Therapy

et al. 2021

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Bladder cancer is a significant public health concern and social burden due to its high recurrence risk. Intravesical drug instillation is the primary therapy for bladder cancer to prevent recurrence. However, the intravesical drug therapeutic effect is limited by bladder penetrating barriers. The inadequate intravesical treatment might cause the low drug concentration in lesions, resulting in a high recurrence/progression rate of bladder cancer. Many strategies to get drugs across bladder penetrating barriers have been developed to improve intravesical treatment, including physical and chemical methods. This review summarizes the classical and updated literature and presents insights into great therapeutic potential strategies to overcome bladder penetrating barriers for improving the intravesical treatment of bladder cancer.

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“…Induces cell recruitment through receptor-influenced endocytosis (Wang et al, 2017a). Providing the ability to deliver various drugs, from anticarcinogens and peptides (Griffin et al, 2017;Li et al, 2021). Several reactions allow the formation of such microgels and nanogels, among them are the thiol-ene chemistry mediated by radicals, the photo-click chemistry of tetrazole-alkene, the oxime, the Dielse-Alder Reaction and the azide cycloaddition, strainpromoted alkyne (Palmese et al, 2019).…”

Section: Hgs Functionalized With Nano and Micromaterialsmentioning

confidence: 99%

Biofunctionalization of hydrogel-based scaffolds for vascular tissue regeneration

López-Gutierrez¹,

Ramos‐Payán²,

Ayala-Ham³

et al. 2023

Front. Mater.

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Congenital and acquired tissular losses due to disease or trauma are a major world health problem. Regenerative therapy aims to fix damaged tissues by directing the natural capacity of a host organism to use biofunctionalized artificial tissue scaffolds. These three-dimensional (3D) scaffolds can be customized with cells and/or bioactive molecules to induce cellular homing and angiogenesis, essential to ensure successful tissue regeneration. Hydrogels (HGs) scaffolds are networks of hydrophilic homopolymers, copolymers, and/or macromers with chemical and biological activities that enhance their cell colonization. The use of HGs in regenerative medicine has shown to be advantageous since HGs can be prepared under clinical-grade conditions and tailored to the specific needs of the replaced tissue. They can be made to emulate native extracellular matrices (ECMs) including physical, mechanical, and chemical cues and resilience properties. These customized HGs can reproduce the natural hygroscopic capacity of the original tissue which improves cellular anchoring, nutrition, and waste disposal. They can enable host molecular and cellular modification conducive to a natural cellular microenvironment, modifying the properties of the scaffold, and improving chemotaxis, cell adhesion, migration, proliferation, differentiation, and angiogenesis; HGs can be created and biofunctionalized with linked growth factors and synthetic peptides tailored to positively influence scaffold colonization and functional biocompatibility. This review aims to collect the most relevant information regarding biofunctionalization of HGs used for vascular tissue regeneration, their biological effects, and their clinical implications. While most biofunctionalized HGs are still under investigation, some of them have been studied in vitro, ex vivo, and in vivo with promising results. In this regard, in vivo studies have shown that biofunctionalized scaffolds with peptides such as chitosan hydrogel with LL-37 promotes angiogenesis and healing of pressure ulcers. Also, the GHK tripeptide is widely used in trials focused on guided tissue remodeling.

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Cell-penetrating peptide CGKRK mediates efficient and widespread targeting of bladder mucosa following focal injury

Cited by 21 publications

References 24 publications

Delivery of Small Molecules by Syndiotactic Peptides for Breast Cancer Therapy

Delivery of Small Molecules by Syndiotactic Peptides for Breast Cancer Therapy

Strategies to Get Drugs across Bladder Penetrating Barriers for Improving Bladder Cancer Therapy

Biofunctionalization of hydrogel-based scaffolds for vascular tissue regeneration

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