scholarly journals Photosensitizer Chlorin e6 Internalization into Tumor Cells in Phospholipid Nanoparticles Conjugated with Peptide Containing the NGR Sequence

2018 ◽  
Vol 1 (4) ◽  
pp. e00063 ◽  
Author(s):  
V.N. Prozorovskiy ◽  
L.V. Kostryukova ◽  
E.I. Korotkevich ◽  
T.I. Torkhovskaya ◽  
G.E. Morozevich ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Amino Acid ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Aminopeptidase N ◽  
Chlorin E6 ◽  
Phospholipid Nanoparticles ◽  
Chlorine E6 ◽  
Targeting Peptide ◽  
Mcf 7

The possibility of increased internalization of the photosensitizer chlorin e6 in tumor cells was investigatedusing soy phosphatidylcholine nanoparticles 20-30 nm with or without attached peptide containing Asn-Gly-Arg (NGR) motif was studied. This amino acid sequence exhibits affinity to aminopeptidase N (CD13), wich is overexpressed in a number of tumor cells and vessels. Nanoparticles with chlorin e6 were prepared with added of distearoylphosphatidylcholine (DSPE) conjugated through PEG with a hexapeptide containing the NGR sequence, and then were incubated with tumor cells НерG2 and MCF-7. Chlorin e6 accumulation in СD13-negative cells (MCF-7) did not depend on the presence of peptide NGR in nanoparticles. However, for НерG2 cells a twofold increase of chlorine e6 internalization was observed as compared with the same particles without NGR. Differences in the response of these two cell lines, differed in expression of aminopeptidase N (APN), suggest the possibility of this protein using for targeted delivery. The prospectivity of usage of phospholipids nanoparticles conjugated with targeting peptide for photodynamic therapy is discussed, taking into account possible variation of APN expression, inherent for many solid tumors.

scholarly journals Chlorin e6 embedded in phospholipid nanoparticles equipped with specific peptides: Interaction with tumor cells with different aminopeptidase N expression

2021 ◽  
Vol 134 ◽  
pp. 111154
Author(s):  
Tatyana I. Torkhovskaya ◽  
Lyubov V. Kostryukova ◽  
Yulia A. Tereshkina ◽  
Elena G. Tikhonova ◽  
Galina E. Morozevich ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Aminopeptidase N ◽  
Chlorin E6 ◽  
Phospholipid Nanoparticles

Targeted drug delivery system for doxorubicin based on a specific peptide and phospholipid nanoparticles

2020 ◽  
Vol 66 (6) ◽  
pp. 464-468
Author(s):  
L.V. Kostryukova ◽  
Y.A. Tereshkina ◽  
E.I. Korotkevich ◽  
V.N. Prozorovsky ◽  
T.I. Torkhovskaya ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Cells ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Breast Adenocarcinoma ◽  
Control Line ◽  
Phospholipid Nanoparticles ◽  
Significant Difference ◽  
Targeted Drug ◽  
Cd13 Receptor

Doxorubicin is one of the widely known and frequently used chemotherapy drugs for the treatment of various types of cancer, the use of which is difficult due to its high cardiotoxicity. Targeted drug delivery systems are being developed to reduce side effects. One of the promising components as vector molecules (ligands) are NGR-containing peptides that are affinity for the CD13 receptor, which is expressed on the surface of many tumor cells and tumor blood vessels. Previously, a method was developed for preparing a composition of doxorubicin embedded in phospholipid nanoparticles with a targeted fragment in the form of an ultrafine emulsion. The resulting composition was characterized by a small particle size (less than 40 nm) and a high degree of incorporation of doxorubicin (about 93%) into transport nanoparticles. When assessing the penetrating ability and the degree of binding to the surface of fibrosarcoma cells (HT-1080), it was shown that when the composition with the targeted fragment was added to the cells, the level of doxorubicin was almost 2 times higher than that of the liposomal form of doxorubicin, i.e. the drug in the system with the targeted peptide penetrated the cell better. At the same time, on the control line of breast adenocarcinoma cells (MCF-7), which do not express the CD13 receptor on the surface, there was not significant difference in the level of doxorubicin in the cells. The data obtained allow us to draw preliminary conclusions about the prospects of targeted delivery of doxorubicin to tumor cells when using a peptide conjugate containing an NGR motif and the further need for its comprehensive study.

Preclinical photodynamic therapy in Spain 2: Liposome vectorization of photosensitizers; Different strategies, different outcomes

2009 ◽  
Vol 13 (04n05) ◽  
pp. 537-543 ◽  
Author(s):  
Margarita Mora ◽  
M. Lluïsa Sagristá
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
General Trend ◽  
Secondary Effects ◽  
Tumor Cell Death ◽  
Cytotoxic Effects ◽  
Selective Targeting ◽  
Selective Delivery ◽  
Pathological Tissues

Photodynamic therapy is an emerging modality of cancer treatment based on the use of photosensitizing drugs, which accumulate selectively in tumor cells. Exposure to visible light induces local cytotoxic effects that lead selectively to tumor cell death in the irradiated region, thereby minimizing the risk and extension of unwanted secondary effects. One of the goals sought in the development of photodynamic therapy drugs is the selective targeting of tumor cells. As a general trend, the indiscriminate delivery of drugs is being increasingly substituted by the selective delivery to pathological tissues which can be achieved by embedding them into transporters that actively recognize differential factors of tumor cells and tissues as compared to healthy ones. Likewise, the chemical modification of the photosensitizers is a valid strategy to change the subcellular localization of the drug. The use of liposomes as transporters for targeted delivery of drugs has attracted particular attention during the last two decades. After a period characterized by the skepticism expressed by certain scientists in the field of drug delivery, interest in liposomes was rejuvenated by the introduction of fresh ideas from membrane biophysics.

scholarly journals Amino acid derivatives of natural chlorins as a platform for the creation of targeted photosensitizers in oncology

2021 ◽  
Vol 15 (6) ◽  
pp. 16-33
Author(s):  
A. F. Mironov ◽  
P. V. Ostroverkhov ◽  
S. I. Tikhonov ◽  
V. A. Pogorilyy ◽  
N. S. Kirin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Methionine Sulfoximine ◽  
Amino Acid Derivatives ◽  
Resonance Spectroscopy ◽  
Biochemical Processes ◽  
Derivatives Of

Objectives. This study aims to obtain the amino acid derivatives of chlorophyll a and bacteriochlorophyll a for the targeted delivery of pigments to tumor foci. This will increase biocompatibility and, as a result, reduce toxic side effects. In addition to photodynamic efficiency, an additional cytotoxic effect is expected for the obtained conjugates of photosensitizers (PSs) with amino acids. This is owing to the participation of the latter in intracellular biochemical processes, including interaction with the components of the glutathione antioxidant system, leading to the vulnerability of tumor cells to oxidative stress.Methods. In this work, we have implemented the optimization of the structure of a highly efficient infrared PS based on O-propyloxim-N-propoxybacteriopurpurinimide (DPBP), absorbing at 800 nm and showing photodynamic efficacy for the treatment of deep-seated and pigmented tumors, by introducing L-lysine, L-arginine, methionine sulfoximine (MSO), and buthionine sulfoximine (BSO) methyl esters. The structure of the obtained compounds was proved by mass spectrometry and nuclear magnetic resonance spectroscopy, and the photoinduced cytotoxicity was studied in vitro on the HeLa cell line.Results. Conjugates of DPBP with amino acids and their derivatives, such as lysine, arginine, MSO, and BSO have been prepared. The chelating ability of DPBP conjugate with lysine was shown, and its Sn(IV) complex was obtained.Conclusions. Biological testing of DPBP with MSO and BSO showed a 5–6-fold increase in photoinduced cytotoxicity compared to the parent DPBP PS. Additionally, a high internalization of pigments by tumor cells was found, and the dark cytotoxicity (in the absence of irradiation) of DPBP-MSO and DPBP-BSO increased fourfold compared to the initial DPBP compound. This can be explained by the participation of methionine derivatives in the biochemical processes of the tumor cell.

scholarly journals Spectroscopic Investigation of Chlorin-Based Photosensitizers in Polymer Matrix

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Antonina Naumenko ◽  
Nataliya Kutsevol
Keyword(s):  
Drug Delivery ◽  
Photodynamic Therapy ◽  
Optical Absorption ◽  
Tumor Cells ◽  
Polymer Matrix ◽  
Spectroscopic Investigation ◽  
Chlorin E6 ◽  
Optical Absorption Spectra ◽  
Trimethyl Ether ◽  
Derivatives Of

Chlorin e6 and its derivatives are the basis of a number of drugs used in medicine in the treatment of various diseases, including cancer, by photodynamic therapy. Nonpolar derivatives of Chlorin e6—dimethyl ether of Chlorin e6 (DME Ce6) and trimethyl ether of Chlorin e6 (TME Ce6)—are actively studied for application during photodynamic therapy. In this work, based on the electron optical absorption spectra, the interaction of photosensitizer molecules with branched star-like copolymer dextran-graft-polyacrylamide in anionic form was investigated and the possibility of using the latter as a carrier for drug delivery to tumor cells was suggested.

Preparation of chlorin e6–monoclonal antibody conjugate and its effect for photodynamic therapy

2001 ◽  
Vol 05 (05) ◽  
pp. 486-489 ◽  
Author(s):  
SHUN-ICHIRO OGURA ◽  
YUTAKA FUJITA ◽  
TOSHIAKI KAMACHI ◽  
ICHIRO OKURA
Keyword(s):  
Monoclonal Antibody ◽  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Binding Affinity ◽  
Cellular Uptake ◽  
Chlorin E6 ◽  
Peptide Bonds ◽  
High Binding ◽  
Antibody Conjugate ◽  
High Binding Affinity

Chlorin e6 ( Ce 6) was conjugated with anti-tumor monoclonal antibody ( IgG 2 b ) to increase its binding affinity for tumors. The Ce 6 was activated by N -hydroxysuccinimide and directly conjugated with IgG 2 b ( IgG 2 b – Ce 6) via peptide bonds. An average of 11 Ce 6 molecules were coupled to each IgG2b molecule. IgG 2 b – Ce 6 showed high cellular uptake in tumor cells and high photocytotoxicity. These results indicate IgG 2 b – Ce 6 is a good photosensitizer with high binding affinity to tumor cells.

Effect of Cell-Penetrating Arginine Peptide on Interaction of Photosensitizer Chlorin e6 Incorporated into Phospholipid Nanoparticles with Tumor Cells

2019 ◽  
Vol 167 (3) ◽  
pp. 347-350 ◽  
Author(s):  
L. V. Kostryukova ◽  
E. I. Korotkevich ◽  
G. E. Morozevich ◽  
E. F. Kolesanova ◽  
M. V. Mel’nikova ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Chlorin E6 ◽  
Phospholipid Nanoparticles ◽  
Cell Penetrating
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