Cell-penetrating peptide: a means of breaking through the physiological barriers of different tissues and organs
TL;DR: An emphasis is focused on summarizing the novel insights and achievements of CPPs in surmounting the natural membrane barriers during the last 5 years.
About: This article is published in Journal of Controlled Release.The article was published on 2019-07-16. It has received 81 citations till now. The article focuses on the topics: Cell-penetrating peptide.
Citations
More filters
TL;DR: Recent developments and innovations in preclinical studies and clinical trials based on using CPP for improved delivery, which have revealed that CPPs or CPP-based delivery systems present outstanding diagnostic therapeutic delivery potential.
Abstract: Cell-penetrating peptides (CPPs) are short peptides (fewer than 30 amino acids) that have been predominantly used in basic and preclinical research during the last 30 years. Since they are not only capable of translocating themselves into cells but also facilitate drug or CPP/cargo complexes to translocate across the plasma membrane, they have potential applications in the disease diagnosis and therapy, including cancer, inflammation, central nervous system disorders, otologic and ocular disorders, and diabetes. However, no CPPs or CPP/cargo complexes have been approved by the US Food and Drug Administration (FDA). Many issues should be addressed before translating CPPs into clinics. In this review, we summarize recent developments and innovations in preclinical studies and clinical trials based on using CPP for improved delivery, which have revealed that CPPs or CPP-based delivery systems present outstanding diagnostic therapeutic delivery potential.
220 citations
TL;DR: The present review could further facilitate the design of ACPs and increase efficacious ACP therapy in the near future.
Abstract: Cancer is currently ineffectively treated using therapeutic drugs, and is also able to resist drug action, resulting in increased side effects following drug treatment. A novel therapeutic strategy against cancer cells is the use of anticancer peptides (ACPs). The physicochemical properties, amino acid composition and the addition of chemical groups on the ACP sequence influences their conformation, net charge and orientation of the secondary structure, leading to an effect on targeting specificity and ACP‑cell interaction, as well as peptide penetrating capability, stability and efficacy. ACPs have been developed from both naturally occurring and modified peptides by substituting neutral or anionic amino acid residues with cationic amino acid residues, or by adding a chemical group. The modified peptides lead to an increase in the effectiveness of cancer therapy. Due to this effectiveness, ACPs have recently been improved to form drugs and vaccines, which have sequentially been evaluated in various phases of clinical trials. The development of the ACPs remains focused on generating newly modified ACPs for clinical application in order to decrease the incidence of new cancer cases and decrease the mortality rate. The present review could further facilitate the design of ACPs and increase efficacious ACP therapy in the near future.
141 citations
Cites background from "Cell-penetrating peptide: a means o..."
...Medical application for drug delivery requires biologically active conjugates (cargoes) and/or binding peptides (‘guiding missile’) to reach specific intracellular targets (102-104)....
[...]
TL;DR: While there have been advances in understanding the limitations of peptides for oral delivery, low membrane permeability, metabolism, and high clearance rates continue to hamper progress.
126 citations
Cites background from "Cell-penetrating peptide: a means o..."
...Another approach to promote permeability of cyclic peptides is to appendCPPs [264]....
[...]
TL;DR: The most recent construction strategies and release patterns of various cancer cell subcellular-targeting nanoformulations are discussed, aiming at providing guidance in the overall design of precise nanomedicine.
Abstract: Therapeutic efficacy against cancer relies heavily on the ability of the therapeutic agents to reach their final targets. The optimal targets of most cancer therapeutic agents are usually biological macromolecules at the subcellular level, which play a key role in carcinogenesis. Therefore, to improve the therapeutic efficiency of drugs, researchers need to focus on delivering not only the therapeutic agents to the target tissues and cells but also the drugs to the relevant subcellular structures. In this review, we discuss the most recent construction strategies and release patterns of various cancer cell subcellular-targeting nanoformulations, aiming at providing guidance in the overall design of precise nanomedicine. Additionally, future challenges and potential perspectives are illustrated in the hope of enhancing anticancer efficacy and accelerating the translational progress of precise nanomedicine.
63 citations
Journal Article•
TL;DR: In this paper, a cell-penetrating peptide, which was modified on both termini with an alkyl chain, was anchored to the liposomal surface in a constrained and deactivated form.
Abstract: Herein we report on the development of a novel method of constraining a cell-penetrating peptide, which can be used to trigger transport of liposomes into cells upon in this case radiation with UV-light. A cell-penetrating peptide, which was modified on both termini with an alkyl chain, was anchored to the liposomal surface in a constrained and deactivated form. Since one of the two alkyl chains was connected to the peptide via a UV-cleavable linker, disconnection of this alkyl chain upon irradiation led to the exposure of the cell-penetrating peptide, and mediated the transport of the entire liposome particle into cells.
60 citations
References
More filters
TL;DR: Signal transducer and activator of transcription proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer, and STAT3 is a promising target to redirect inflammation for cancer therapy.
Abstract: Commensurate with their roles in regulating cytokine-dependent inflammation and immunity, signal transducer and activator of transcription (STAT) proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer. Persistently activated STAT3 and, to some extent, STAT5 increase tumour cell proliferation, survival and invasion while suppressing anti-tumour immunity. The persistent activation of STAT3 also mediates tumour-promoting inflammation. STAT3 has this dual role in tumour inflammation and immunity by promoting pro-oncogenic inflammatory pathways, including nuclear factor-kappaB (NF-kappaB) and interleukin-6 (IL-6)-GP130-Janus kinase (JAK) pathways, and by opposing STAT1- and NF-kappaB-mediated T helper 1 anti-tumour immune responses. Consequently, STAT3 is a promising target to redirect inflammation for cancer therapy.
3,564 citations
TL;DR: Experiments using radioactive protein show that tat becomes localized to the nucleus after uptake and suggest that chloroquine protects tat from proteolytic degradation, raising the possibility that, under some conditions, tat might act as a viral growth factor to stimulate viral replication in latently infected cells or alter expression of cellular genes.
2,733 citations
TL;DR: In this paper, the authors review the barriers to the delivery of cancer therapeutics and summarize strategies that have been developed to overcome these barriers and discuss design considerations for optimizing the nanoparticles to tumors.
Abstract: Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. While the enhanced permeability and retention effect has served as a key rationale for using nanoparticles to treat solid tumors, it does not enable uniform delivery of these particles to all regions of tumors in sufficient quantities. This heterogeneous distribution of therapeutics is a result of physiological barriers presented by the abnormal tumor vasculature and interstitial matrix. These barriers are likely to be responsible for the modest survival benefit offered by many FDA-approved nanotherapeutics and must be overcome for the promise of nanomedicine in patients to be realized. Here, we review these barriers to the delivery of cancer therapeutics and summarize strategies that have been developed to overcome these barriers. Finally, we discuss design considerations for optimizing the delivery of nanoparticles to tumors.
2,688 citations
TL;DR: Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound for delivery of macromolecules and vaccines.
Abstract: Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase its impact on medicine.
2,595 citations
TL;DR: By reducing the size of the transposed sequence, it is concluded that Pro-Lys- lys- Lys-Arg-L Lys-Val can act as a nuclear location signal and may represent a prototype of similar sequences in other nuclear proteins.
2,551 citations