Mitochondria-targeting and cell-penetrating peptides-co-modified HPMA copolymers for enhancing therapeutic efficacy of α-tocopheryl succinate

2018 ◽  
Vol 6 (46) ◽  
pp. 7674-7683 ◽  
Author(s):  
Yanxi Liu ◽  
Qiuyi Li ◽  
Xiaofeng Xiong ◽  
Yuan Huang ◽  
Zhou Zhou
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Therapeutic Efficacy ◽  
Effective Means ◽  
Cell Penetrating Peptides ◽  
Hpma Copolymers ◽  
Tocopheryl Succinate ◽  
Cell Penetrating ◽  
Mitochondria Targeting

Targeting drugs at mitochondria may provide an effective means of inducing cell death for cancer therapy.

scholarly journals Self-assembly of mitochondria-specific peptide amphiphiles amplifying lung cancer cell death through targeting the VDAC1–hexokinase-II complex

2019 ◽  
Vol 7 (30) ◽  
pp. 4706-4716 ◽  
Author(s):  
Dan Liu ◽  
Angelina Angelova ◽  
Jianwen Liu ◽  
Vasil M. Garamus ◽  
Borislav Angelov ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cell ◽  
Self Assembly ◽  
Cell Penetrating Peptides ◽  
Lung Cancer Cell ◽  
Hexokinase Ii ◽  
Cancer Cell Death ◽  
Cell Penetrating ◽  
Specific Peptide

Novel cell-penetrating peptides self-assemble into ellipsoid-shape nanostructures which amplified the apoptotic stimuli by weakening the VDAC1–HK-II interaction.

The design of peptide-grafted graphene oxide targeting the actin cytoskeleton for efficient cancer therapy

2017 ◽  
Vol 53 (83) ◽  
pp. 11433-11436 ◽  
Author(s):  
Qilin Yu ◽  
Bing Zhang ◽  
Jianrong Li ◽  
Mingchun Li
Keyword(s):  
Graphene Oxide ◽  
Cancer Therapy ◽  
Actin Cytoskeleton ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating

Graphene oxide (GO) nanosheets grafted with actin targeting and cell penetrating peptides were designed.

scholarly journals Utilization of a cell-penetrating peptide-adaptor for delivery of HPV protein E2 into cervical cancer cells to arrest cell growth and promote cell death

2020 ◽  
Author(s):  
Julia C. LeCher ◽  
Hope L. Didier ◽  
Robert L. Dickson ◽  
Lauren R. Slaughter ◽  
Juana C. Bejarano ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Penetrating Peptides ◽  
Viral Integration ◽  
E2 Protein ◽  
Cell Penetrating ◽  
Cervical Cancer Cells ◽  
E6 And E7

AbstractCervical cancer is the second leading cause of cancer deaths in women worldwide. Human papillomavirus (HPV) is the causative agent of nearly all forms of cervical cancer, which arises upon viral integration into the host genome and concurrent loss of regulatory gene E2. E2 protein regulates viral oncoproteins E6 and E7. Loss of E2 upon viral integration results in unregulated expression and activity of E6 and E7, which promotes carcinogenesis. Previous studies using gene-based delivery show that reintroduction of E2 into cervical cancer cell lines can reduce proliferative capacity and promote apoptosis. However, owing in part to limitations on transfection in vivo, E2 reintroduction has yet to achieve therapeutic usefulness. A promising new approach is protein-based delivery systems utilizing cell-penetrating peptides (CPPs). CPPs readily traverse the plasma membrane and are able to carry with them biomolecular ‘cargos’ to which they are attached. Though more than two decades of research have been dedicated to their development for delivery of biomolecular therapeutics, the full potential of CPPs has yet to be realized as the field is hindered by the tendency of CPP-linked cargos to be trapped in endosomes as well as having significant off-target potential in vivo. Using a CPP-adaptor system that reversibly binds cargo thereby overcoming the endosomal entrapment that hampers other CPP methods, bioactive E2 protein was delivered into living cervical cancer cells, resulting in inhibition of cellular proliferation and promotion of cell death in a time- and dose-dependent manner. The results suggest that this nucleic acid- and virus-free delivery method could be harnessed to develop novel, effective protein therapeutics for treatment of cervical cancer.

Cell Penetrating Mechanism of Bax Inhibiting Peptides.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4298-4298
Author(s):  
Jose A. Gomez ◽  
Tomoyuki Yoshida ◽  
Minh Lam ◽  
Clark W. Distelhorst ◽  
Shigemi Matsuyama
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Fluorescent Dyes ◽  
Cultured Cells ◽  
Cell Penetrating Peptides ◽  
Dependent Manner ◽  
Cell Penetration ◽  
New Members ◽  
Cell Penetrating ◽  
High Degree

Abstract Plasma membrane is known to have a high degree of selectivity for molecular trafficking, and it does not allow the penetration of peptides larger than 3 amino acids. Previously known exceptions of large peptides that penetrate the plasma membrane are the Arginine rich peptides such as human immunodeficiency virus (HIV)-tat peptides. However, the mechanism of cell penetration of these peptides is largely unknown. Bax Inhibiting Peptides (BIP) are penta-peptides derived from the Bax binding domain of Ku70. At present, three types of BIP have been developed. Those are: VPMLK, VPTLK, and VPALR. All of these three BIPs directly bind Bax and inhibit Bax-mediated cell death in cultured cells as well as in animal study. Surprisingly, BIPs are cell permeable and autonomously enter the cytoplasm of the cells within 1 hr. Therefore BIPs are recognized as new members of cell penetration peptides. In this study, we investigated the mechanism of cell penetration of BIPs. DAMI cells (a human megakaryocyte cell line) and HeLa cells were used to investigate the detailed mechanism of cell penetration of BIPs. To detect the cell entry of BIPs, fluorescent dyes (fluorescein or tetramethylrodhamine) were conjugated to the N-terminus of BIPs and the cytoplasmic localization of BIPs was confirmed by confocal microscopy. Cell Penetration activities of BIPs were detected at 1 uM concentration in the culture medium. The significant accumulation of BIPs in the cytoplasm were detected within 1 hour of incubation both at 4 °C and 37 °C, suggesting that ATP-independent mechanism of cell penetration of BIP exists. However, cellular uptake of BIPs reaches plateau at 100 uM at 4 °C, whereas it increases in a dose dependent manner up to 1 mM at 37 °C without any sign of cytotoxicity. These results suggest that there are at least two mechanisms contributing to the cell penetration of BIPs that are, “ATP-independent (4 °C)” and “ATP-dependent (37 °C)” mechanisms. In addition to BIPs, we generated a series of mutated BIPs that do not bind Bax but retain cell-penetrating activities. We performed competition assay using fluorescence dye-labeled and non-labeled BIP (and the mutant BIPs), and the preliminary results suggest that there is a specific receptor for each peptide for its delivery into the cells. Our data also indicates that BIPs can deliver a cargo molecule (e.g. fluorescent dye) with at least the same molecular weight. Unlike other cell penetrating peptides, BIP has minimum toxicity due to its nature to inhibit Bax-mediated cell death. Along with the new data showing that BIP protects cells from pathological damages in cell culture and animal model, we will discuss the potential application of BIPs as a new type of drug delivery tool.

scholarly journals Inhibition of regulated cell death by cell-penetrating peptides

2016 ◽  
Vol 73 (11-12) ◽  
pp. 2269-2284 ◽  
Author(s):  
Stefan Krautwald ◽  
Christin Dewitz ◽  
Fred Fändrich ◽  
Ulrich Kunzendorf
Keyword(s):  
Cell Death ◽  
Cell Penetrating Peptides ◽  
Regulated Cell Death ◽  
Cell Penetrating

scholarly journals Increasing the potential of cell-penetrating peptides for cancer therapy using a new pentagonal scaffold

2019 ◽  
Vol 860 ◽  
pp. 172554 ◽  
Author(s):  
Diana Duarte ◽  
Alexandra G. Fraga ◽  
Jorge Pedrosa ◽  
Fátima Martel ◽  
Nuno Vale
Keyword(s):  
Cancer Therapy ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating

Co-delivery of anticancer drugs and cell penetrating peptides for improved cancer therapy

2020 ◽  
Author(s):  
Xiao Fu ◽  
Guiqiang Zhang ◽  
Yulin Zhang ◽  
Haifeng Sun ◽  
Shuang Yang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Anticancer Drugs ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating

scholarly journals Pharmacological inhibition of Bax-induced cell death: Bax-inhibiting peptides and small compounds inhibiting Bax

2019 ◽  
Vol 244 (8) ◽  
pp. 621-629 ◽  
Author(s):  
Kelsey Jensen ◽  
David Jasen WuWong ◽  
Sean Wong ◽  
Mieko Matsuyama ◽  
Shigemi Matsuyama
Keyword(s):  
Cell Death ◽  
Cell Penetrating Peptides ◽  
Peptide Group ◽  
Successful Development ◽  
Cell Penetrating ◽  
Potential Applications ◽  
Future Direction ◽  
Programed Cell Death

Bax is an essential mediator of mitochondria-dependent programed cell death. Bax belongs to the Bcl-2 family of proteins and its activities are regulated through interaction with other member proteins in the Bcl-2 family. To date, several apoptosis-inducing drugs activating Bax have been developed, and some of them are already in the market as therapeutics against cancer. However, at present, there are no clinically effective pharmacological Bax inhibitors protecting essential cells. Previously, we developed Bax-Inhibiting Peptides (BIPs) that belong to the peptide group of Cell-Penetrating Peptides (CPPs). CPPs have the ability to deliver cargo molecules into the cell. In this review, we will describe the mechanism of action of BIPs together with the recent applications of BIPs in disease models in vitro and in vivo. However, BIPs have several limitations in their use to treat human diseases, and other types of Bax inhibitors need to be developed for future therapeutics. Recently, several groups reported the successful development of novel small compounds inhibiting Bax. We will review these Bax inhibitors to discuss current strategies to develop pharmacological Bax inhibitors. Impact statement Bax induces mitochondria-dependent programed cell death. While cytotoxic drugs activating Bax have been developed for cancer treatment, clinically effective therapeutics suppressing Bax-induced cell death rescuing essential cells have not been developed. This mini-review will summarize previously reported Bax inhibitors including peptides, small compounds, and antibodies. We will discuss potential applications and the future direction of these Bax inhibitors.

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