Chlorine e6 in Phospholipid Nanoparticles with Specific Targeting and Penetrating Peptides as Prospective Composition for Photodynamic Therapy of Malignant Neoplasms

2020 ◽  
Vol 14 (2) ◽  
pp. 174-179 ◽  
Author(s):  
L. V. Kostryukova ◽  
A. D. Plyutinskaya ◽  
A. A. Pankratov ◽  
E. I. Korotkevich ◽  
V. N. Prozorovskiy ◽  
...  
2019 ◽  
Vol 65 (6) ◽  
pp. 507-512
Author(s):  
L.V. Kostryukova ◽  
A.D. Plyutinskaya ◽  
A.A. Pankratov ◽  
E.I. Korotkevich ◽  
V.N. Prozorovskiy ◽  
...  

Cytotoxic and photoinduced activity of chlorine e6 (Ce6) in phospholipid nanoparticles with specific tumor targeting and cell-penetrating peptides was studied in vitro using human fibrosarcoma cells HT-1080. It was shown, that the binding of cell-penetrating peptide R7 – alone or combined with the peptide containing specific targeting motif NGR (Asn-Gly-Arg) – resulted in 3-fold decrease of Ce6 photoinduced activity as compared with that in nanoparticles without peptides (IC50 values were 0.7 μg/ml and 2.1 μg/ml, respectively). The NGR influence was unexpectedly low – less than 20% (IC50 1.7 μg/ml). This suggests the more importance of Ce6 cell penetration in this case, than of NGR-mediated targeting. The effect of inclusion of both peptides on the total cytotoxicity of Ce6 was minimal (10-16 times less than on the specific photoinduced activity). The obtained results – together with earlier shown effects on improvement of the pharmacokinetics of Ce6 in vivo after its embedding into phospholipid nanoparticles – indicate the prospects of using the obtained phospholipid nanoparticles system for photodynamic therapy.


2018 ◽  
Vol 1 (4) ◽  
pp. e00063 ◽  
Author(s):  
V.N. Prozorovskiy ◽  
L.V. Kostryukova ◽  
E.I. Korotkevich ◽  
T.I. Torkhovskaya ◽  
G.E. Morozevich ◽  
...  

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.


2018 ◽  
Vol 23 (3-6) ◽  
pp. 134-142
Author(s):  
A. E Tseimakh ◽  
A. F Lazarev ◽  
V. A Kurtukov ◽  
M. E Tseimakh ◽  
Ia. N Shoykhet

Data from the global oncology statistics shows that pancreatic cancer is at the 4th place in the world for mortality in men and women, having the lowest five-year life expectancy among gastrointestinal tumors with an average median survival of no more than 6 months. Along with it, malignant neoplasms of the biliary tract are rare in the frequency of occurrence of the nosological group of diseases, which, however, are on the second place in terms of the level of malignancy among the neoplasms of the liver. Both nosologies in the vast majority are not subject to radical treatment, being the object of palliative treatment due to late diagnosis. Despite the establishment of new medical technologies, the main method of treating of these nosologies remains surgical. However, at the time of detection and diagnosis less than 20% of patients have a resectable process, and, moreover, even patients with a resectable tumor are often not subjected to radical surgical treatment due to dissemination of the tumor at the time of surgery, which reduces the postoperative five-year survival of this cancer: 25-30% in patients without metastases to regional lymph nodes and about 10% in patients with metastases to regional lymph nodes. Due to the low efficiency of the surgical method, there are searched new methods of complex treatment, new drugs and chemotherapy regimens, as well as radiotherapy regimens, however, with the improvement of methods for diagnosing cancer in the past 20-25 years, neither the prognosis nor survival of patients nor the percentage of early diagnosis of cancer of the pancreas did not significantly improve. A new and promising method for the treatment of malignant neoplasms of the pancreas and the biliary tract is photodynamic therapy, the undoubted advantage of which is low toxicity, selective effect only on cancer cells at the fundamental level, contributing depending on the duration of exposure to their autophagy, apoptosis or necrosis. And, although PDT has drawbacks connected with side effects of PDT, such as gastrointestinal bleeding, obstruction of the duodenum and hemorrhagic pancreonecrosis, and with insufficient knowledge and lack of clear recommendations, but the PDT method is certainly a promising method in both radical and in palliative complex therapy of malignant neoplasms of the pancreas and biliary tract, which requires further study.


2020 ◽  
Vol 9 (2) ◽  
pp. 18-28
Author(s):  
E. F. Stranadko ◽  
A. V. Baranov ◽  
V. A. Duvansky ◽  
A. I. Lobakov ◽  
V. A. Morokhotov ◽  
...  

The problem of treating patients with malignant neoplasms of the extrahepatic bile ducts and the large duodenal papilla remains relevant due to the growing incidence, high mortality, and a pronounced decrease in the quality of life of patients, despite the radical surgery. The purpose of this study was to evaluate the effectiveness of photodynamic therapy (PDT) in inoperable patients with malignant tumors of these localizations.The study is based on the treatment of 79 patients with adenocarcinoma of large duodenal papilla and extrahepatic bile ducts. 29 patients received palliative bile drainage operations with PDT. 50 patients in the control group only had palliative bile drainage operations. Patients in the study group received from 1 to 3 PDT courses in a year. In total, 29 patients received 52 PDT courses. The tolerance to the method and the life expectancy of patients were evaluated. The median survival of patients who underwent PDT was 18 months (11–60 months); in the control group – 11.5 months. PDT, in combination with bile drainage operation, is an effective method for the treatment of inoperable patients with malignant neoplasms of the extrahepatic bile ducts and the large duodenal papilla in the absence of severe complications and with easy tolerance to therapy by patients. For the treatment and prolongation of life of patients whose radical surgical treatment is associated with a high risk of death, PDT seems to be the best treatment option. Results of PDT treatment for cancer of this localization are comparable with the results of radical surgeries and exceed those for palliative surgeries.


2021 ◽  
Vol 10 (3) ◽  
pp. 32-38
Author(s):  
Y. A. Panaseykin ◽  
E. V. Filonenko ◽  
F. E. Sevrukov ◽  
V. V. Polkin ◽  
P. A. Isaev ◽  
...  

Oral mucosa cancer is a common disease with relatively low survival rates. The standard for the treatment of malignant neoplasms (MNO) of the oral mucosa is the surgical method, chemotherapy and / or radiation therapy. With the introduction of modern protocols and the improvement of current treatment methods, the increase in survival is insignificant due to the development of local and distant relapses, the appearance of simultaneous tumors of the oral cavity. Cosmetic and functional results in patients who have undergone complex treatment for oral cancer are often unsatisfactory. There is an obvious need to develop new approaches to treating patients with cancer of the oral mucosa. Photodynamic therapy (PDT) has similar properties. With the development of endoscopic and fiber-optic equipment, the fields of PDT application have significantly expanded. Foci in the oral cavity and oropharynx became available for PDT. The early stages of oral mucosal cancer are optimal for PDT because large surface defects can be treated with minimal complications. Preservation of subepithelial and collagen structures, which is typical for PDT, promotes healing without the formation of scar processes, thereby achieving an ideal cosmetic and functional effect. The use of PDT in the treatment of oral cavity cancer is not limited only to the initial stages in an independent version. It is possible to use PDT in combination with surgical and radiation treatment. In case of massive tumor processes, PDT is used for palliative purposes. The influence of the adaptive immune response under the influence of PDT is being studied.


2021 ◽  
Vol 14 ◽  
Author(s):  
Nathali R B de Lima ◽  
Fernando G de Souza Junior ◽  
Valérie G Roullin ◽  
Kaushik Pal ◽  
Nathalia D da Silva

Background: Cancer is one of the diseases causing society’s fears as a stigma of death and pain. Head and Neck Squamous Cell Carcinoma (HNSCC) is a group of malignant neoplasms of different locations in this region of the human body. It is one of the leading causes of morbidity and mortality in Brazil, because these malignant neoplasias, in most cases, are diagnosed in late phases. Surgical excision, chemotherapy and radiotherapy encompass the forefront of antineoplastic therapy; however, the numerous side effects associated with these therapeutic modalities are well known. Some treatments present enough potential to help or replace conventional treatments, such as Magnetic Hyperthermia and Photodynamic Therapy. Such approaches require the development of new materials at the nanoscale, able to carry out the loading of their active components while presenting characteristics of biocompatibility mandatory for biomedical applications. Objective: This work aims to make a bibliographical review of HNSCC treatments. Recent techniques proven effective in other types of cancer were highlighted and raised discussion and reflections on current methods and possibilities of enhancing the treatment of HNSCC. Method: The study was based on a bibliometric research between the years 2008 and 2019 using the following keywords: Cancer, Head and Neck Cancer, Chemotherapy, Radiotherapy, Photodynamic Therapy, and Hyperthermia. Results: A total of 5.151.725 articles were found, 3.712.670 about cancer, 175.470 on Head and Neck Cancer, 398.736 on Radiotherapy, 760.497 on Chemotherapy, 53.830 on Hyperthermia, and 50.522 on Photodynamic Therapy. Conclusion: The analysis shows that there is still much room for expanding research, especially for alternative therapies since most of the studies still focus on conventional treatments and on the quest to overcome their side effects. The scientific community needs to keep looking for more effective therapies generating fewer side effects for the patient. Currently, the so-called alternative therapies are being used in combination with the conventional ones, but the association of these new therapies shows great potential, in other types of cancer, to improve the treatment efficacy.


2008 ◽  
Vol 5 ◽  
pp. S45
Author(s):  
A.M. Shubina ◽  
M.A. Kaplan ◽  
V.N. Kapinus ◽  
I.S. Spichenkova ◽  
V.V. Polkin

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