scholarly journals Tumor Activated Cell Penetrating Peptides to Selectively Deliver Immune Modulatory Drugs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 365
Author(s):  
Dina V. Hingorani ◽  
Maria F. Camargo ◽  
Maryam A. Quraishi ◽  
Stephen R. Adams ◽  
Sunil J. Advani
Keyword(s):  
Immune System ◽  
Cancer Therapy ◽  
Tumor Tissue ◽  
Tissue Concentration ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Peptide Drug ◽  
Systemic Delivery ◽  
Drug Conjugate ◽  
Cell Penetrating

Recent advances in immunotherapy have revolutionized cancer therapy. Immunotherapies can engage the adaptive and innate arms of the immune system. Therapeutics targeting immune checkpoint inhibitors (i.e., CTLA-4; PD-1, and PD-L1) have shown efficacy for subsets of cancer patients by unleashing an adaptive antitumor immune response. Alternatively, small molecule immune modulators of the innate immune system such as toll-like receptor (TLR) agonists are being developed for cancer therapy. TLRs function as pattern recognition receptors to microbial products and are also involved in carcinogenesis. Reisquimod is a TLR 7/8 agonist that has antitumor efficacy. However, systemic delivery free resiquimod has proven to be challenging due to toxicity of nonspecific TLR 7/8 activation. Therefore, we developed a targeted peptide-drug conjugate strategy for systemic delivery of resiquimod. We designed an activatable cell penetrating peptide to deliver resiquimod specifically to the tumor tissue while avoiding normal tissues. The activatable cell penetrating peptide (ACPP) scaffold undergoes enzymatic cleavage by matrix metalloproteinases 2/9 in the extracellular matrix followed by intracellular lysosomal cathepsin B mediated release of the free resiquimod. Importantly, when conjugated to ACPP; the tumor tissue concentration of resiquimod was more than 1000-fold greater than that of surrounding non-cancerous tissue. Moreover, systemic ACPP-resiquimod delivery produced comparable therapeutic efficacy to localized free resiquimod in syngeneic murine tumors. These results highlight a precision peptide-drug conjugate delivery.

Enhanced oral absorption of insulin using colon-specific nanoparticles co-modified with amphiphilic chitosan derivatives and cell-penetrating peptides

2019 ◽  
Vol 7 (4) ◽  
pp. 1493-1506 ◽  
Author(s):  
Feng Guo ◽  
Ting Ouyang ◽  
Taoxing Peng ◽  
Xiuying Zhang ◽  
Baogang Xie ◽  
...  
Keyword(s):  
Oral Absorption ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Chitosan Derivative ◽  
Chitosan Derivatives ◽  
Cell Penetrating

In this study, amphipathic chitosan derivative (ACS) and cell-penetrating peptide (CPP) co-modified colon-specific nanoparticles (CS-CPP NPs) were prepared and evaluated.

scholarly journals siRNA suppression of hTERT using activatable cell-penetrating peptides in hepatoma cells

2015 ◽  
Vol 35 (2) ◽  
Author(s):  
Hua Li ◽  
Jiwen He ◽  
Huimin Yi ◽  
Guoan Xiang ◽  
Kaiyun Chen ◽  
...  
Keyword(s):  
Hepatoma Cells ◽  
Cell Penetrating Peptides ◽  
Matrix Metalloproteinase 2 ◽  
Cell Penetrating Peptide ◽  
G1 Arrest ◽  
Telomerase Reverse Transcriptase ◽  
Human Telomerase Reverse Transcriptase ◽  
Htert Gene ◽  
Cell Penetrating ◽  
Human Telomerase

In the present study, we delivered human telomerase reverse transcriptase (hTERT) siRNA into SMMC-7721 hepatoma cells using a matrix metalloproteinase-2 (MMP2)-activatable cell-penetrating peptide (aCPP). The siRNA subsequently induced down-regulation of the hTERT gene and G1-arrest, implicating the utility of this delivery system in cancer therapy.

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.

Antibody-Assisted Delivery of a Peptide–Drug Conjugate for Targeted Cancer Therapy

2018 ◽  
Vol 16 (1) ◽  
pp. 165-172 ◽  
Author(s):  
Hyungjun Kim ◽  
Dobeen Hwang ◽  
Minsuk Choi ◽  
Soyoung Lee ◽  
Sukmo Kang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Peptide Drug ◽  
Targeted Cancer Therapy ◽  
Drug Conjugate ◽  
Assisted Delivery

scholarly journals A comparison of acyl-moieties for noncovalent functionalization of PLGA and PEG-PLGA nanoparticles with a cell-penetrating peptide

RSC Advances ◽  
2021 ◽  
Vol 11 (57) ◽  
pp. 36116-36124
Author(s):  
Omar Paulino da Silva Filho ◽  
Muhanad Ali ◽  
Rike Nabbefeld ◽  
Daniel Primavessy ◽  
Petra H. Bovee-Geurts ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Plga Nanoparticles ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Noncovalent Functionalization ◽  
Cell Penetrating ◽  
A Cell

Noncovalent functionalization with acylated cell-penetrating peptides achieves an efficient cellular uptake of PLGA and PEG-PLGA nanoparticles.

scholarly journals Stimuli-Sensitive Cell Penetrating Peptide-Modified Nanocarriers

Processes ◽  
2019 ◽  
Vol 7 (10) ◽  
pp. 727 ◽  
Author(s):  
Perche
Keyword(s):  
Therapeutic Index ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Cellular Internalization ◽  
Normal Tissues ◽  
Formidable Challenge ◽  
Cell Penetrating ◽  
Stimuli Sensitive ◽  
Responsive Cell

The integration of drugs into nanocarriers favorably altered their pharmacodynamics and pharmacokinetics compared to free drugs, and increased their therapeutic index. However, selective cellular internalization in diseased tissues rather than normal tissues still presents a formidable challenge. In this chapter I will cover solutions involving environment-responsive cell-penetrating peptides (CPPs). I will discuss properties of CPPs as universal cellular uptake enhancers, and the modifications imparted to CPP-modified nanocarriers to confine CPP activation to diseased tissues.

Cell-penetrating-peptide-based delivery of oligonucleotides: an overview

2007 ◽  
Vol 35 (4) ◽  
pp. 775-779 ◽  
Author(s):  
R. Abes ◽  
A.A. Arzumanov ◽  
H.M. Moulton ◽  
S. Abes ◽  
G.D. Ivanova ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Peptide Delivery ◽  
Cell Penetrating Peptide ◽  
Cellular Internalization ◽  
Structure Activity ◽  
Cell Penetrating ◽  
Transactivator Of Transcription ◽  
Endocytic Vesicles ◽  
Oligonucleotide Analogues ◽  
Phosphorodiamidate Morpholino Oligomers

Cationic CPPs (cell-penetrating peptides) have been used largely for intracellular delivery of low-molecular-mass drugs, biomolecules and particles. Most cationic CPPs bind to cell-associated glycosaminoglycans and are internalized by endocytosis, although the detailed mechanisms involved remain controversial. Sequestration and degradation in endocytic vesicles severely limits the efficiency of cytoplasmic and/or nuclear delivery of CPP-conjugated material. Re-routing the splicing machinery by using steric-block ON (oligonucleotide) analogues, such as PNAs (peptide nucleic acids) or PMOs (phosphorodiamidate morpholino oligomers), has consequently been inefficient when ONs are conjugated with standard CPPs such as Tat (transactivator of transcription), R9 (nona-arginine), K8 (octalysine) or penetratin in the absence of endosomolytic agents. New arginine-rich CPPs such as (R-Ahx-R)4 (6-aminohexanoic acid-spaced oligo-arginine) or R6 (hexa-arginine)–penetratin conjugated to PMO or PNA resulted in efficient splicing correction at non-cytotoxic doses in the absence of chloroquine. SAR (structure–activity relationship) analyses are underway to optimize these peptide delivery vectors and to understand their mechanisms of cellular internalization.

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