Cell Penetrating Peptide Uptake by Human Tissue

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P35-P35 ◽  
Author(s):  
Nopawan Vorasubin ◽  
Quyen To Nguyen ◽  
Emilia Olson ◽  
Todd A Aguilera ◽  
Tao Jiang ◽  
...  
Keyword(s):  
Human Tissue ◽  
Normal Tissue ◽  
Human Cancer ◽  
Active Form ◽  
Standardized Uptake Value ◽  
Cell Penetrating Peptide ◽  
Cancer Tissue ◽  
Cell Penetrating ◽  
Human Cancer Tissue

Objective 1) Assess activatable cell penetrating peptide (ACPP) uptake by human tissue. 2) Compare ACPP uptake in normal and cancer tissue. Methods ACPPs are peptides that become activated for cellular uptake by cleavage in the presence of specific proteases. Fluorescently tagging ACPPs and designing a cleavage site recognized by proteases abundant in cancer allows for selective uptake and imaging. Cleavable ACPPs consist of L-amino acids linkers, while uncleavable linkers consist of corresponding D-isomers. To assess ACPP uptake by human tissue, we imaged freshly ressected surgical specimens following incubation with ACPP. Uptake was analyzed by measuring average fluorescent intensities (AFI) for histologically identified areas of cancer and normal tissue. Standardized uptake value (SUV) measurements, which represents fluorescence uptake per given tissue weight, and zymography were also performed. Results Average cancer-to-normal AFI ratio when treated with cleavable ACPP was 2.6±0.6 (p=0.003) and with uncleavable control was 1.4±0.5 (p=0.5). Considering cancer tissue alone, average AFI was 22.5 ±2.2 when treated with cleavable and 11.4 ±1.2 when treated with uncleavable ACPP (p=0.004). Tissue SUV when treated with cleavable ACPP was 2.5±0.8mg-1, whereas tissue treated with control ACPP was 1.7±1.0mg-1 (p=0.24). Zymography results show that inactive protease is ubiquitous in cancer and normal tissue while active form is more abundant in cancer. Conclusions In freshly resected human cancer tissue, uptake of cleavable ACPP is ∼2-fold greater than that of uncleavable ACPP. Furthermore, cleavable ACPP uptake is ∼2.5-fold greater in cancer compared to normal tissue. This differential uptake can potentially be used for in vivo imaging of cancer to guide surgical resection.

18F-Labeled phosphopeptide-cell-penetrating peptide dimers with enhanced cell uptake properties in human cancer cells

2012 ◽  
Vol 39 (8) ◽  
pp. 1202-1212 ◽  
Author(s):  
Susan Richter ◽  
Vincent Bouvet ◽  
Melinda Wuest ◽  
Ralf Bergmann ◽  
Joerg Steinbach ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Cell Uptake ◽  
Cell Penetrating Peptide ◽  
Human Cancer Cells ◽  
Cell Penetrating

One-Step Transformation from Rofecoxib to a COX-2 NIR Probe for Human Cancer Tissue/Organoid Targeted Bioimaging

2021 ◽  
Vol 4 (3) ◽  
pp. 2723-2731
Author(s):  
Lijun Xie ◽  
Renfu Li ◽  
Biyun Zheng ◽  
Zuoxu Xie ◽  
Xuefen Fang ◽  
...  
Keyword(s):  
Human Cancer ◽  
Cancer Tissue ◽  
One Step ◽  
Cox 2 ◽  
Human Cancer Tissue

Cell-Penetrating Peptide-Mediated Nanovaccine Delivery

2021 ◽  
Vol 22 ◽  
Author(s):  
Jizong Jiang
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cell Penetrating Peptide ◽  
Antigen Delivery ◽  
Efficient Manner ◽  
Antigen Uptake ◽  
Cell Penetrating ◽  
The Stability ◽  
Antigen Presenting

Abstract: Vaccination with small antigens, such as proteins, peptides, or nucleic acids, is used to activate the immune system and trigger the protective immune responses against a pathogen. Currently, nanovaccines are undergoing development instead of conventional vaccines. The size of nanovaccines is in the range of 10–500 nm, which enables them to be readily taken up by cells and exhibit improved safety profiles. However, low-level immune responses, as the removal of redundant pathogens, trigger counter-effective activation of the immune system invalidly and present a challenging obstacle to antigen recognition and its uptake via antigen-presenting cells (APCs). In addition, toxicity can be substantial. To overcome these problems, a variety of cell-penetrating peptide (CPP)-mediated vaccine delivery systems based on nanotechnology have been proposed, most of which are designed to improve the stability of antigens in vivo and their delivery into immune cells. CPPs are particularly attractive components of antigen delivery. Thus, the unique translocation property of CPPs ensures that they remain an attractive carrier with the capacity to deliver cargo in an efficient manner for the application of drugs, gene transfer, protein, and DNA/RNA vaccination delivery. CPP-mediated nanovaccines can enhance antigen uptake, processing, and presentation by APCs, which are the fundamental steps in initiating an immune response. This review describes the different types of CPP-based nanovaccines delivery strategies.

scholarly journals Control of MYC-dependent apoptotic threshold by a co-amplified ubiquitin E3 ligase UBR5

2019 ◽  
Author(s):  
Xi Qiao ◽  
Ying Liu ◽  
Maria Llamazares Prada ◽  
Abhishekh Gupta ◽  
Alok Jaiswal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Ubiquitin Ligase ◽  
Breast Cancer Cells ◽  
Human Cancer ◽  
Cancer Therapeutics ◽  
Cancer Tissue ◽  
Basal Type

AbstractMYC protein expression has to be tightly controlled to allow for maximal cell proliferation without inducing apoptosis. Here we discover UBR5 as a novel MYC ubiquitin ligase and demonstrate how it functions as a molecular rheostat to prevent excess accumulation of MYC protein. UBR5 effects on MYC protein stability are independent on N-terminal FBW7 degron of MYC. Endogenous UBR5 inhibition induces MYC protein expression and activates MYC target genes. Moreover, UBR5 governs MYC-dependent phenotypes in vivo in Drosophila. In cancer cells, UBR5-mediated MYC protein suppression diminishes cell killing activity of cancer therapeutics. Further, we demonstrate that UBR5 dominates MYC protein expression at the single-cell level in human basal-type breast cancer tissue. Myc and Ubr5 are co-amplified in MYC-driven human cancer types, and UBR5 controls MYC-mediated apoptotic threshold in co-amplified basal type breast cancer cells. In summary, UBR5 is a novel MYC ubiquitin ligase and an endogenous rheostat for MYC protein expression in vivo. Clinically, expression of UBR5 may be important for protection of breast cancer cells from drug-induced, and MYC-dependent, apoptosis.

scholarly journals Effective In Vivo Topical Delivery of siRNA and Gene Silencing in Intact Corneal Epithelium Using a Modified Cell-Penetrating Peptide

2019 ◽  
Vol 17 ◽  
pp. 891-906 ◽  
Author(s):  
Davide Schiroli ◽  
María J. Gómara ◽  
Eleonora Maurizi ◽  
Sarah D. Atkinson ◽  
Laura Mairs ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Corneal Epithelium ◽  
Topical Delivery ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating

scholarly journals A212 CHROMOFUNGIN PROTECTS AGAINST DSS-INDUCED COLITIS BY REGULATING P-53 APOPTITIC PATHWAY

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 84-85
Author(s):  
A Diarra ◽  
N Eissa ◽  
J Ghia
Keyword(s):  
B Cell Lymphoma ◽  
Peritoneal Macrophages ◽  
Cell Penetrating Peptide ◽  
Peptide Motif ◽  
Apoptotic Pathway ◽  
Apoptosis Pathway ◽  
Cell Penetrating ◽  
Vehicle Treatment ◽  
A Cell

Abstract Background Development of ulcerative colitis is associated with epithelial apoptosis mediated by p53-apoptotic pathway through the activation B-cell lymphoma 2 (Bcl-2), Bcl-2 associated-X protein (BAX) and Bcl-2 antagonist/killer-1 (BAK1) proteins. Chromofungin (CHR), a chromogranin-A derived peptide expressing a cell penetrating peptide motif, decreased the severity of colitis via the suppression of mucosal and pro-inflammatory macrophages-related p53-dependent apoptosis. Aims We aimed to investigate a) whether the gene profile expression of apoptosis could be extended to other p53-associated genes; b) whether the gene expression of some of the p53-apoptosis marker could be confirmed by protein analysis; and c) whether due to the cell penetrating peptide motif, CHR could enter into peritoneal macrophages. Methods UC-related colitis was induced in C57BL/6 mice (7 weeks) by administering dextran sulfate sodium (DSS) (5%, 5 days). Preventive CHR (2.5 mg/kg/day) or vehicle treatment started 1-day before colitis induction and lasted for 5-days. Profiler™ PCR Array was performed to screen a panel of 84 genes representative of the p53 signal pathway in colitic whole mucosa distal colonic samples treated or not with CHR. Western blot analysis was performed to confirm individual protein changes. Naïve macrophages were plated overnight and nonadherent cells were removed the next day. Cells were incubated with rhodamined CHR (4 ul) for 5, 10, 20, 30 min before washing and fixing them, detection was made via confocal microscopy. Results In colitic conditions, an up regulation of 26 genes associated to the p53-dependent apoptosis pathway were detected including Apaf1, Bax, Bbc3, Bcl2, Cradd, Fadd, Cul9, Pmaip1, Tnfrsf10b. In vivo CHR treatment decreased significantly the colitis and was associated with a significant downregulation of 19 genes including the 9 aforementioned when compared with biopsies from colitic groups. Compared to untreated groups, colitic mice treated with CHR demonstrated a significant decrease of BAX and BAK protein and the apoptotic ER stress inducer marker, X-Binding Protein 1. A large number of peritoneal macrophages displayed rhodamine within the all intracellular compartment. The presence of the peptide inside the cell can be visible as early as 5 min and the signal gradually increases. Conclusions CHR decreases the inflammatory process via the suppression of a large number of p53-related apoptotic proteins. CHR quickly enters the macrophage but the exact mechanism of entrance needs to be further defined. Targeting functional analysis of CHR may lead in the future to novel therapeutics for UC. Funding Agencies CCCNSERC

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