On November 14, 2019 The MISIS National Science and Technology Laboratory Biomedical Laboratory Science Team Conducted an Intravital (Live Tissue) Study of the Targeted Drug Delivery Mechanism based on liposomes for the treatment of malignant tumors (Press release, Misis university, NOV 14, 2019, View Source [SID1234551341]). It has been found that the immune cells of the body’s neutrophils increase the effectiveness of drug delivery for tumor treatment by 30%. The results have been published in the international scientific journal ACS Nano .
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Liposomes – artificially created adipose vesicles – penetrate the tumor due to the increased permeability and retention effect (in English EPR).
The EPR effect appears to be due to the excessive proliferation of blood vessels caused by an abnormal need for oxygen and tumor nutrition. As part of the pathological growth, huge pores up to 200 nm in diameter appear on the walls of blood vessels. In addition, the growth of the tumor causes compression of the lymphatic vessels and prevents the normal flow of intercellular fluid. Thus, liposomes penetrate the tumor and can not exit due to impaired lymphatic drainage.
It is assumed that because of the EPR effect, liposomes can only penetrate the tumor, not the healthy tissue. But is that true? And what’s going on inside the ship?
Scientists at the MISIS National University of Science and Technology’s biomedical nanomaterials laboratory investigated drug delivery in healthy mouse tissues and various types of malignancies: breast cancer, prostate cancer, and melanoma . Observations were made using an intravital microscope, which allows direct study of processes within a living organism.
"The first conclusion we drew from this study is that two types of liposome penetration from blood vessels to tissues occur within living tissues. A micro-leak is a small isolated accumulation of liposomes around a vessel. This process is useless for the treatment of tumors, as it does not allow the drug to reach the tumor cells. In addition, micro-leaks have been detected in healthy tissues, which explains the toxicity of liposome-based drugs used in a modern clinic. " , Said Viktor Naumenko , author of the work, researcher in the laboratory of biomedical nanomaterials National University of Science and Technology MISIS.
The second most interesting observation is that neutrophils, a type of white blood cell and an immune cell of the body, promote leakage to the tumor tissue. When the neutrophil leaves the vessel through the "door ajar" in the vascular wall, the liposomes manage to penetrate the tumor. According to the results obtained by the scientific team, neutrophils increase by a third the efficiency of the penetration of liposomes in the tumor.
This discovery reveals a clear pattern: neutrophils increase the vascular permeability of the tumor during the targeted administration of liposome-based drugs and therefore increase the chances of healing. In addition, this only occurs in the case of a micro-leak , a large, diffuse "cloud" of liposomes that penetrates deep into the tumor, and thus ensures targeted drug delivery.
"The distinction between two types of leaks is important for understanding the functioning of liposome drugs. Our results indicate not only that micro-leaks do not contribute to the penetration of drugs in tumor cells, but also that they are responsible for its undesirable accumulation in healthy tissues. The therapeutic effect is obtained thanks to the macro-leaks, and neutrophils can help strengthen it. " , Said Viktor Naumenko .