Cell-Penetrating Peptide-Mediated Nanovaccine Delivery

Antigen Delivery ◽

Efficient Manner ◽

Antigen Uptake ◽

Cell Penetrating ◽

The Stability ◽

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.

Cell-penetrating Peptides: Efficient Vectors for Vaccine Delivery

Current Drug Delivery ◽

10.2174/1567201816666190123120915 ◽

2019 ◽

Vol 16 (5) ◽

pp. 430-443 ◽

Cited By ~ 14

Author(s):

Jieru Yang ◽

Yacheng Luo ◽

Mohini Anjna Shibu ◽

Istvan Toth ◽

Mariusz Skwarczynskia

Keyword(s):

Drug Transport ◽

Vaccine Delivery ◽

Cell Penetrating Peptides ◽

Delivery Systems ◽

Antigen Delivery ◽

Antigen Uptake ◽

Cell Penetrating ◽

The Stability ◽

Subunit vaccines are composed of pathogen fragments that, on their own, are generally poorly immunogenic. Therefore, the incorporation of an immunostimulating agent, e.g. adjuvant, into vaccine formulation is required. However, there are only a limited number of licenced adjuvants and their immunostimulating ability is often limited, while their toxicity can be substantial. To overcome these problems, a variety of vaccine delivery systems have been proposed. Most of them are designed to improve the stability of antigen in vivo and its delivery into immune cells. Cell-penetrating peptides (CPPs) are especially attractive component of antigen delivery systems as they have been widely used to enhance drug transport into the cells. Fusing or co-delivery of antigen with CPPs can enhance antigen uptake, processing and presentation by antigen presenting cells (APCs), which are the fundamental steps in initiating an immune response. This review describes the different mechanisms of CPP intercellular uptake and various CPP-based vaccine delivery strategies.

Antibody Response after Vaccination with Antigen-Pulsed Dendritic Cells

The International Journal of Biological Markers ◽

10.1177/172460080401900306 ◽

2004 ◽

Vol 19 (3) ◽

pp. 213-220

Author(s):

F. Battaini ◽

D. Besusso ◽

L. Sfondrini ◽

A. Rossini ◽

D. Morelli ◽

...

Keyword(s):

Dendritic Cells ◽

Immune System ◽

Immune Responses ◽

Antibody Response ◽

Cancer Patients ◽

Antibody Production ◽

Tumor Antigens ◽

Antigen Uptake ◽

Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system capable of initiating immune responses to antigens. It is also well documented that cancer patients often experience anergy against tumor antigens. In this study we selected the best protocol for inducing the production of antibodies against the HER2 oncoprotein using DCs to overcome anergy. Murine DCs were pulsed in vitro, using different protocols, with recombinant HER2 fused to a human Fc (in order to improve DC antigen uptake) and were used to vaccinate mice. The obtained results indicate that antigen-pulsed DCs can induce an antibody response and that adding CpG after antigen pulsing greatly increases anti-HER2 antibody production.

Intracellular Delivery of Oxaliplatin Conjugate via Cell Penetrating Peptide for the Treatment of Colorectal Carcinoma in vitro and in vivo

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2021.120904 ◽

2021 ◽

pp. 120904

Author(s):

Tejinder Singh ◽

Dong Hyun Kang ◽

Tae Wan Kim ◽

Hye Jeong Kong ◽

Jae Sung Ryu ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Intracellular Delivery ◽

Cell Penetrating

A Novel Recombinant Fcγ Receptor-Targeted Survivin Combines with Chemotherapy for Efficient Cancer Treatment

Biomedicines ◽

10.3390/biomedicines9070806 ◽

2021 ◽

Vol 9 (7) ◽

pp. 806

Author(s):

Chiao-Chieh Wu ◽

Chen-Yi Chiang ◽

Shih-Jen Liu ◽

Hsin-Wei Chen

Keyword(s):

Immune Responses ◽

Fusion Protein ◽

Human Cancer ◽

Formyl Peptide Receptor ◽

Antigen Delivery ◽

Potential Candidate ◽

Fcγ Receptor ◽

Formyl Peptide ◽

Efficient Uptake

Formyl peptide receptor-like 1 inhibitor (FLIPr), an Fcγ receptor (FcγR) antagonist, can be used as a carrier to guide antigen-FLIPr fusion protein to FcγR then enhances antigen-specific immune responses. Survivin, a tumor-associated antigen, is over-expressed in various types of human cancer. In this study, we demonstrate that recombinant survivin-FLIPr fusion protein (rSur-FLIPr) binds to FcγRs, and efficient uptake by dendritic cells in vivo. In addition, rSur-FLIPr alone stimulates survivin-specific immune responses, which effectively suppresses the tumor growth. The antitumor immunities are through TAP-mediated and CD8-dependent pathways. Furthermore, preexisting anti-FLIPr antibody does not abolish antitumor responses induced by rSur-FLIPr immunization. These results suggest that FLIPr is an effective antigen delivery vector and can be repeatedly used. Combination of chemotherapy with rSur-FLIPr treatment reveals a great benefit to tumor-bearing mice. Altogether, these findings suggest that rSur-FLIPr is a potential candidate for efficient cancer therapy.

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

Molecular Therapy — Nucleic Acids ◽

10.1016/j.omtn.2019.07.017 ◽

2019 ◽

Vol 17 ◽

pp. 891-906 ◽

Cited By ~ 8

Author(s):

Davide Schiroli ◽

María J. Gómara ◽

Eleonora Maurizi ◽

Sarah D. Atkinson ◽

Laura Mairs ◽

...

Keyword(s):

Gene Silencing ◽

Corneal Epithelium ◽

Topical Delivery ◽

Cell Penetrating

Tumor-Homing Cell-Penetrating Peptide Linked to Colloidal Mesoporous Silica Encapsulated (-)-Epigallocatechin-3-gallate as Drug Delivery System for Breast Cancer Therapy in Vivo

ACS Applied Materials & Interfaces ◽

10.1021/acsami.5b05618 ◽

2015 ◽

Vol 7 (32) ◽

pp. 18145-18155 ◽

Cited By ~ 37

Author(s):

Jie Ding ◽

Jing Yao ◽

Jingjing Xue ◽

Rong Li ◽

Bo Bao ◽

...

Keyword(s):

Breast Cancer ◽

Drug Delivery ◽

Cancer Therapy ◽

Mesoporous Silica ◽

Drug Delivery System ◽

Breast Cancer Therapy ◽

Cell Penetrating ◽

Tumor Homing

Abstract 2050: Cell penetrating peptide, ST101, disrupts ATF5 regulation of anti-apoptotic Bcl-2 family proteins, resulting in induction of cancer cell death in vitro and tumor growth inhibition/regression in vivo

10.1158/1538-7445.sabcs18-2050 ◽

2019 ◽

Author(s):

Jim A. Rotolo ◽

Rick Ramirez ◽

Mark Koester ◽

Siok Leong ◽

Lila Ghamsari ◽

...

Keyword(s):

Cell Death ◽

Tumor Growth ◽

Growth Inhibition ◽

Cancer Cell ◽

Tumor Growth Inhibition ◽

Cancer Cell Death ◽

Cell Penetrating

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

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.211 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 84-85

Author(s):

A Diarra ◽

N Eissa ◽

J Ghia

Keyword(s):

B Cell Lymphoma ◽

Peritoneal Macrophages ◽

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

Red blood cell–derived nanoerythrosome for antigen delivery with enhanced cancer immunotherapy

Science Advances ◽

10.1126/sciadv.aaw6870 ◽

2019 ◽

Vol 5 (10) ◽

pp. eaaw6870 ◽

Cited By ~ 31

Author(s):

Xiao Han ◽

Shufang Shen ◽

Qin Fan ◽

Guojun Chen ◽

Edikan Archibong ◽

...

Keyword(s):

Blood Cells ◽

Tumor Recurrence ◽

Tumor Antigens ◽

Tumor Model ◽

Antigen Delivery ◽

Tumor Cell Membrane ◽

Programmed Death ◽

Delivery Platform ◽

Erythrocytes or red blood cells (RBCs) represent a promising cell-mediated drug delivery platform due to their inherent biocompatibility. Here, we developed an antigen delivery system based on the nanoerythrosomes derived from RBCs, inspired by the splenic antigen-presenting cell targeting capacity of senescent RBCs. Tumor antigens were loaded onto the nanoerythrosomes by fusing tumor cell membrane–associated antigens with nanoerythrosomes. This tumor antigen–loaded nanoerythrosomes (nano-Ag@erythrosome) elicited antigen responses in vivo and, in combination with the anti–programmed death ligand 1 (PD-L1) blockade, inhibited the tumor growth in B16F10 and 4T1 tumor models. We also generated a tumor model showing that “personalized nano-Ag@erythrosomes” could be achieved by fusing RBCs and surgically removed tumors, which effectively reduced tumor recurrence and metastasis after surgery.