scholarly journals The anticancer efficacy of paclitaxel liposomes modified with low-toxicity hydrophobic cell-penetrating peptides in breast cancer: an in vitro and in vivo evaluation

RSC Advances ◽  
2018 ◽  
Vol 8 (43) ◽  
pp. 24084-24093 ◽  
Author(s):  
Qi Zhang ◽  
Jing Wang ◽  
Hao Zhang ◽  
Dan Liu ◽  
Linlin Ming ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Delivery ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
In Vivo Evaluation ◽  
Anticancer Efficacy ◽  
Cell Penetrating ◽  
Low Toxicity

Hydrophobic cell penetrating peptide PFVYLI-modified liposomes have been developed for the targeted delivery of PTX into tumors.

Toxicity Effects of Anthracycline-Converted Herceptin and Azo-Functionalized Fe3O4 Nanoparticles on the Heart of Patients with Breast Cancer Based on Echocardiography

2021 ◽  
Vol 21 (2) ◽  
pp. 878-885
Author(s):  
Li Liu ◽  
Tingting Shen ◽  
Hongfang Liu ◽  
Gen Zhang ◽  
Yongfu Shao
Keyword(s):  
Breast Cancer ◽  
Targeted Delivery ◽  
Combined Therapy ◽  
Drug Carriers ◽  
Temperature Sensitive ◽  
Breast Cancer Patients ◽  
Clinical Value ◽  
Low Toxicity

The multifunctional nano-carrier system can simultaneously achieve multiple functions such as diagnostic imaging, targeted delivery of anti-tumor drugs, and combined therapy. Application potential Fe3O4 magnetic nanoparticles have the characteristics of low toxicity, superparamagnetism and good photothermal properties. Therefore, a multifunctional magnetic nanocarrier with both magnetic targeting and photothermal properties can be prepared by surface modification of Fe3O4 o DOX is an anti-tumor drug widely used in clinical treatment, and its severe toxic and side effects greatly limit its application. In this paper, a temperature-sensitive magnetic nanocarrier was first constructed and proved to have good superparamagnetism, photothermal properties, and biocom-patibility Then, Fe3O4-Azo-DOX drug-loaded nanoparticles were constructed by covalently bonding DOX. The prepared Fe3O4-Azo-DOX nanoparticles have high stability, sensitive photothermal response and low toxicity. Finally, Fe3O4-Azo-DOX was applied to the study of combined photother-motherapy and chemotherapy in vitro and in vivo. Based on Fe3O4 nanoparticles, a temperature-sensitive Fe3O4-Azo nanocarrier was constructed and its related properties were characterized. Furthermore, anthracycline nanodrugs were used in chemotherapy of breast cancer patients, and their effects were analyzed according to echocardiography parameter change. The results show that Fe3O4-Azo nanoparticles have a good photothermal heating effect. MCF-7 breast cancer cells were selected as a model to investigate the cytotoxicity of Fe3O4-Azo. The results proved that they have excellent biocompatibility and can be used as drug carriers. A Fe3O4-Azo nanocarrier was used to load DOX to construct a NIR-responsive nano-drug delivery system. By studying the NIR controlled release of Fe3O4-Azo-DOX under different pH conditions, it can be seen that it has NIR-responsive release function and the best release effect at pH 5.7. It was found that LVEF, LVFS, and E/A were significantly lower after chemotherapy than before (P < 0.05), which had a certain clinical value in cardiotoxicity The in vitro antitumor effect of Fe3O4-Azo-DOX was studied, and the results showed that the combined effect of photothermal-chemotherapy was significantly better than the photothermal treatment based on Fe3O4-Azo carrier alone and the chemotherapy based on free DOX alone.

Novel folate-targeted docetaxel-loaded nanoparticles for tumour targeting: in vitro and in vivo evaluation

RSC Advances ◽  
2016 ◽  
Vol 6 (69) ◽  
pp. 64306-64314 ◽  
Author(s):  
M. H. Han ◽  
Z. T. Li ◽  
D. D. Bi ◽  
Y. F. Guo ◽  
H. X. Kuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Folic Acid ◽  
Cancer Therapy ◽  
Targeted Delivery ◽  
Tumour Targeting ◽  
Breast Cancer Therapy ◽  
In Vivo Evaluation ◽  
Targeted Delivery System

Cholesterol-PEG1000-FA (folic acid) was synthesized as a stabilizer to encapsulate DTX, for the construction of a promising targeted delivery system for breast cancer therapy.

scholarly journals Potassium channels, megapolarization, and water pore formation are key determinants for cationic cell-penetrating peptide translocation into cells

2020 ◽  
Author(s):  
Evgeniya Trofimenko ◽  
Gianvito Grasso ◽  
Mathieu Heulot ◽  
Nadja Chevalier ◽  
Marco A. Deriu ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Pore Formation ◽  
Transmembrane Potential ◽  
Cellular Membrane ◽  
Cell Penetrating Peptides ◽  
Bioactive Molecules ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating

SummaryCell-penetrating peptides (CPPs) allow intracellular delivery of cargo molecules. CPPs provide efficient methodology to transfer bioactive molecules in cells, in particular in conditions when transcription or translation of cargo-encoding sequences is not desirable or achievable. The mechanisms allowing CPPs to enter cells are ill-defined and controversial. This work identifies potassium channels as key regulators of cationic CPP translocation. Using a CRISPR/Cas9-based screening, we discovered that KCNQ5, KCNN4, and KCNK5 positively modulate CPP cellular direct translocation by reducing transmembrane potential (Vm). Cationic CPPs further decrease the Vm to megapolarization values (about −150 mV) leading to the formation of ∼2 nm-wide water pores used by CPPs to access the cell’s cytoplasm. Pharmacological manipulation to lower transmembrane potential boosted CPPs cellular uptake in zebrafish and mouse models. Besides identifying the first genes that regulate CPP translocation, this work characterizes key mechanistic steps used by CPPs to cross cellular membrane. This opens the ground for pharmacological strategies augmenting the susceptibility of cells to capture CPP-linked cargos in vitro and in vivo.

scholarly journals Novel Orthogonally Hydrocarbon-Modified Cell-Penetrating Peptide Nanoparticles Mediate Efficient Delivery of Splice-Switching Antisense Oligonucleotides In Vitro and In Vivo

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1046
Author(s):  
Safa Bazaz ◽  
Tõnis Lehto ◽  
Rahel Tops ◽  
Olof Gissberg ◽  
Dhanu Gupta ◽  
...  
Keyword(s):  
Antisense Oligonucleotides ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Efficient Delivery ◽  
Cell Penetrating ◽  
Peptide Nanoparticles ◽  
Therapeutic Compounds ◽  
Peptide Stapling

Splice-switching therapy with splice-switching oligonucleotides (SSOs) has recently proven to be a clinically applicable strategy for the treatment of several mis-splice disorders. Despite this, wider application of SSOs is severely limited by the inherently poor bioavailability of SSO-based therapeutic compounds. Cell-penetrating peptides (CPPs) are a class of drug delivery systems (DDSs) that have recently gained considerable attention for improving the uptake of various oligonucleotide (ON)-based compounds, including SSOs. One strategy that has been successfully applied to develop effective CPP vectors is the introduction of various lipid modifications into the peptide. Here, we repurpose hydrocarbon-modified amino acids used in peptide stapling for the orthogonal introduction of hydrophobic modifications into the CPP structure during peptide synthesis. Our data show that α,α-disubstituted alkenyl-alanines can be successfully utilized to introduce hydrophobic modifications into CPPs to improve their ability to formulate SSOs into nanoparticles (NPs), and to mediate high delivery efficacy and tolerability both in vitro and in vivo. Conclusively, our results offer a new flexible approach for the sequence-specific introduction of hydrophobicity into the structure of CPPs and for improving their delivery properties.

Arthrospira Platensis Mediated Green Biosynthesis of Silver Nanoparticlesas Breast Cancer Controlling Agent: In-vitro and In-vivo Safety Approach.

2021 ◽  
Author(s):  
Nehal El Deeb ◽  
Mai A. Abo-Eleneen ◽  
Omyma A. Awad ◽  
Atef M. Abo-Shady
Keyword(s):  
Breast Cancer ◽  
Survival Rates ◽  
Arthrospira Platensis ◽  
Active Metabolites ◽  
Protein Marker ◽  
Anticancer Efficacy ◽  
Protein Levels ◽  
Albino Mice

Abstract Biogenic Silver Nanoparticle (bio-AgNPs) is one of the most fascinating nanomaterials used in the biomedical purposes. In the current study, we biosynthesized AgNPs (bio-AgNPs) using Arthrospira platensis(A-bio-AgNPs), Microcystis aeruginosa(M-bio-AgNPs)and Chlorella vulgaris(C-bio-AgNPs) active metabolites and evaluated their anticancer efficacy against breast cancer. The recovered bio-AgNPs were characterized using Scanning and Transmission Electron Microscopy (SEM and TEM) and their safety profiles were monitoring in-vitro on PBMCs cells and in-vivo on Albino mice. The obtained results indicated the safety usage of bio-AgNPs at concentration of 0.1 mg/ml on PBMCs cells and 1.5mg/ml on the Albino mice. The bio-AgNPs displayed dose-dependent cytotoxic effects against HepG-2, CaCO-2 and MCF-7 cell lines by inducing ROS and arresting the treated cells in G0/G1 and sub G0 phases. In addition, A-bio-AgNPs induced breast cancer cellular apoptosis by down regulating the expression of survivin, MMP7, TGF and Bcl2 genes. Upon A-bio-AgNPs treatment, a significant reduction in tumor growth and prolonged survival rates were recorded in breast cancer BALB/c model. Furthermore, A-bio-AgNPs treatment significant decreased theKi 67 protein marker from 60% (in the untreated group) to 20% and increased Caspase 3 protein levels to 65% (in treated groups) comparing with 45% (in Doxorubicin treated groups).

Bax-inhibiting peptides derived from Ku70 and cell-penetrating pentapeptides

2007 ◽  
Vol 35 (4) ◽  
pp. 797-801 ◽  
Author(s):  
J.A. Gomez ◽  
V. Gama ◽  
T. Yoshida ◽  
W. Sun ◽  
P. Hayes ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Protein A ◽  
Cellular Damage ◽  
Toxic Drug ◽  
Cell Penetrating ◽  
Low Toxicity ◽  
Repair Factor ◽  
Green Fluorescent

We found that Ku70, a known DNA repair factor, has a novel function to bind and inhibit Bax (Bcl-2-associated X protein), a key mediator of apoptosis. Pentapeptides derived from the Bax-binding domain of Ku70 were cell-permeable and protected cells from Bax-mediated apoptosis. These pentapeptides were called BIPs (Bax-inhibiting peptides). BIPs may become a useful therapeutic tool to reduce cellular damage. We also generated BIP mutant pentapeptides that do not inhibit Bax, but retain their cell-penetrating activity. Since both BIPs and BIP mutants are cell-permeable, these peptides were designated CPP5s (cell-penetrating pentapeptides). Among the CPP5s discovered, VPTLK (BIP) and KLPVM (BIP mutant) were confirmed to possess protein transduction activity by examination of the delivery of GFP (green fluorescent protein) into cells by these peptides. The mechanism of cell penetration by CPP5s is not known. CPP5s enter the cell at 0 and 4°C. In preliminary studies, various inhibitors of endocytosis and pinocytosis did not show any significant suppression of CPP5 cell entry. CPP5s have very low toxicity in vitro and in vivo and so may be useful tools in order to develop non-toxic drug-delivery technologies.

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