Exosomes are biological nanovesicles that participate in intercellular communication by transferring biologically active chemical compounds (proteins, microRNA, mRNA, DNA, and others). Due to their small size (diameter 40–100 nm) and high biological compatibility, exosomes are promising delivery tools in personalized therapy. Because artificial exosome synthesis methods are not developed yet, the urgent task is to develop an effective and safe way to obtain exosomes from natural sources. Milk is the only exosome-containing biological fluid that is commercially available. In this regard, milk exosomes are unique and promising candidates for new therapeutic approaches to treating various diseases, including cancer. The appearance of side effects during the use of cytotoxic and cytostatic agents is among the main problems in cancer chemotherapy. According to this, the targeted delivery of chemotherapeutic agents can be a potential solution to the toxic effect of chemotherapy. The ability of milk exosomes to carry out biologically active substances to the cell makes them promising tools for oral delivery of chemotherapeutic agents. This review is devoted to the methods of milk exosome isolation, their biological components, and prospects for their use in cancer treatment.

Obesity during pregnancy increases the risk of obesity in offspring. To correct the offspring development in obese mothers, it is necessary to reveal the molecular mechanisms that mediate the influence of the maternal environment on the offspring ontogenesis. Leptin levels increase with obesity. In C57Bl mice, the Ау mutation is associated with elevated blood levels of leptin in pregnant females and exerts a gender-specific effect on the metabolic phenotype of mature offspring. Aim: to study the influence of Ау mutation on sensitivity to diet-induced obesity in male and female offspring, on fetal and placental weight and on the expression of genes in the placentas of the fetuses of different sexes. Body weight and food intake on a standard and an obesogenic diet, fetal and placental weights on pregnancy days 13 and 18, and gene expression of glucose transporters (GLUT1, GLUT3), neutral amino acid transporters (SNAT1, SNAT2, SNAT4), insulin-like growth factor 2 IGF2 and its receptor IGF2R were measured in male and female offspring of и ɑ/ɑ (control) and Ау/ɑ mothers. Ay mutation influenced the body weight only in male offspring, which consumed a standard diet, and did not influence obesity development in both male and female offspring. The weight of fetuses and placentas in Ау/ɑ as compared to ɑ/ɑ  females was reduced on day 13 of pregnancy and was not different on day 18. On day 13 of pregnancy, the mRNA levels of the examined genes did not differ in placentas of male and female fetuses in ɑ/ɑ  females. In Ау/ɑ females, the gene expression of GLUT1, GLUT3, SNAT1 and SNAT4 was reduced in female placentas compared to male placentas. The results suggest that the sex-specific transcription response of placentas to elevated leptin levels in pregnant Ау/ɑ females can mediate the gender-specific impact of Ау mutation on the offspring metabolism in postnatal life.

Horse milk exosomes have been isolated and purified via the developed technology, and their microscopic and biochemical analyzes have been carried out. It was shown that the gel-filtration on the Ultrogel A4 resin can significantly reduce the amount of milk proteins co-isolated with exosomes. Methods for the isolation of nucleic acids from the preparations at various purification stages were proposed, and the content of nucleic acids in horse milk exosomes was analyzed. It was demonstrated that horse milk exosome preparations are not toxic to human cell cultures. The prospects of using horse milk exosomes for drug delivery into cell cultures are discussed. exosomes, horse milk, exosome isolation, nucleic acids The research carried out by S.E. Sedykh, A.E. Kuleshova and E.E. Burkova was financially supported by the Russian Scientific Foundation (project no. 18-74-10055 to S.E. Sedykh); the research by G.A. Nevinskii (MALDI TOF MS/MS analysis) was supported by the basic budget financing project no. ICBFM SB RAS # АААА-А17-117020210023-1 (to G.A. Nevinsky).