scholarly journals Permeability evaluation of gemcitabine-CPP6 conjugates in Caco-2 cells

ADMET & DMPK ◽  
2020 ◽  
Author(s):  
Abigail Ferreira ◽  
Sara Moreira ◽  
Rui Lapa ◽  
Nuno Vale
Keyword(s):  
Tumor Regression ◽  
Cell Penetrating Peptides ◽  
Treatment Efficiency ◽  
Adverse Side Effects ◽  
Cell Penetrating ◽  
Initial Tumor ◽  
Enzymatic Inactivation ◽  
Transporter Deficiency ◽  
Permeability Evaluation ◽  
Isolated Cell

Cancer is one of the most alarming diseases due to its high mortality and still increasing incidence rate. Currently available treatments for this condition present several shortcomings and new options are continuously being developed and evaluated, aiming at increasing the overall treatment efficiency and reducing associated adverse side effects. Gemcitabine has proven activity and is used in chemotherapy. However, its therapeutic efficiency is limited by its low bioavailability as a result of rapid enzymatic inactivation. Additionally, tumor cells often develop drug resistance after initial tumor regression related to transporter deficiency. We have previously developed three gemcitabine conjugates with cell-penetrating hexapeptides (CPP6) to facilitate intracellular delivery of this drug while also preventing enzymatic deamination. The bioactivity of these new prodrugs was evaluated in different cell lines and showed promising results. Here, we assessed the absorption and permeability across Caco-2 monolayers of these conjugates in comparison with gemcitabine and the respective isolated cell-penetrating peptides (CPPs). CPP6-2 (KLPVMW) and respective Gem-CPP6-2 conjugate showed the highest permeability in Caco-2 cells.  

scholarly journals Cell Penetrating Peptide-Based Self-Assembly for PD-L1 Targeted Tumor Regression

2021 ◽  
Vol 22 (24) ◽  
pp. 13314
Author(s):  
Feng Guo ◽  
Junfeng Ke ◽  
Zhengdong Fu ◽  
Wenzhao Han ◽  
Liping Wang
Keyword(s):  
Self Assembly ◽  
Tumor Regression ◽  
Cell Penetrating Peptides ◽  
Electronic Interactions ◽  
Continuous Sequence ◽  
Cell Penetrating ◽  
Good Biocompatibility ◽  
Covalently Linked

Cell penetrating peptides (CPPs) are peptides that can directly adapt to cell membranes and then permeate into cells. CPPs are usually covalently linked to the surface of nanocarriers to endow their permeability to the whole system. However, hybrids with lipids or polymers make the metabolism much more sophisticated and even more difficult to determine. In this study, we present a continuous sequence of 18 amino acids (FFAARTMIWY(d-P)GAWYKRI). It forms nanospheres around 170 nm, which increase slightly after loading with siRNA and DOX. Notably, it can be internalized by cancer cells mainly through electronic interactions and PD-L1-mediated endocytosis. Compared with poly-l-lysine and polyethyleneimine, it has a much higher efficiency (about four times) of gene transduction while lowering toxicity. In the treatment of cancer, it causes apoptosis (21%) and inhibits the expression of SURVIVIN protein in vitro. In vivo, it shows good biocompatibility as there are no changes in mice’s body weight. When administering peptide-siRNA-DOX, tumor growth is inhibited the most (about three times). These results above prove the sequence to be a good candidate for gene therapy and drug delivery.

Oncolytic Coxsackievirus and the Mechanisms of its Effects on Cancer: A Narrative Review

2020 ◽  
Vol 16 ◽  
Author(s):  
Ali Ahmadi ◽  
Hadi Esmaeili Gouvarchin Ghaleh ◽  
Ruhollah Dorostkar ◽  
Mahdieh Farzanehpour ◽  
Masoumeh Bolandian
Keyword(s):  
Genetic Disease ◽  
Control Cell ◽  
Gene Mutations ◽  
Therapeutic Agents ◽  
Cell Penetrating Peptides ◽  
Triggered Release ◽  
New Techniques ◽  
Viral Therapy ◽  
Cell Penetrating ◽  
Cancer Cell Targeting

Abstract:: Cancer is a genetic disease triggered by gene mutations, which control cell growth and their functionality inherited from previous generations. The targeted therapy of some tumors was not especially successful. A host of new techniques can be used to treat aptamer-mediated targeting, cancer immunotherapy, cancer stem cell (CSC) therapy, cell-penetrating peptides (CPPs), hormone therapy, intracellular cancer cell targeting, nanoparticles, and viral therapy. These include chemical-analog conjugation, gene delivery, ligand-receptor-based targeting, prodrug therapies, and triggered release strategies. Virotherapy is a biotechnological technique for turning viruses into therapeutic agents by the reprogramming of viruses to cure diseases. In several tumors, including melanoma, multiple myeloma, bladder cancer, and breast cancer, the oncolytic capacity of oncolytic Coxsackievirus has been studied. The present study aims to assess oncolytic Coxsackievirus and its mechanisms of effect on cancer cells.

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