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Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery
장호충,김효석,김은혜,한건희,장영지,김예리,이종원,신상철,김은경,김선화,양유수 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00
Background Recently, increased attention has been given on exosomes as ideal nanocarriers of drugs owing to their intrinsic properties that facilitate the transport of biomolecular cargos. However, large-scale exosome production remains a major challenge in the clinical application of exosome-based drug delivery systems. Considering its biocompatibility and stability, bovine milk is a suitable natural source for large-scale and stable exosome production. Because the active-targeting ability of drug carriers is essential to maximize therapeutic efficacy and minimize side effects, precise membrane functionalization strategies are required to enable tissue-specific delivery of milk exosomes with difficulty in post-isolation modification. Methods In this study, the membrane functionalization of a milk exosome platform modified using a simple postinsertion method was examined comprehensively. Exosomes were engineered from bovine milk (mExo) with surfacetunable modifications for the delivery of tumor-targeting doxorubicin (Dox). The surface modification of mExo was achieved through the hydrophobic insertion of folate (FA)-conjugated lipids. Results We have confirmed the stable integration of functionalized PE-lipid chains into the mExo membrane through an optimized post-insertion technique, thereby effectively enhancing the surface functionality of mExo. Indeed, the results revealed that FA-modified mExo (mExo-FA) improved cellular uptake in cancer cells via FA receptor (FR)-mediated endocytosis. The designed mExo-FA selectively delivered Dox to FR-positive tumor cells and triggered notable tumor cell death, as confirmed by in vitro and in vivo analyses. Conclusions This simple and easy method for post-isolation modification of the exosomal surface may be used to develop milk-exosome-based drug delivery systems.
( Bohyun Yun ),( Younghoon Kim ),( Dong June Park ),( Sangnam Oh ) 한국축산학회(구 한국동물자원과학회) 2021 한국축산학회지 Vol.63 No.3
Mammalian milk including microRNAs (miRNAs) as a novel class of noncoding RNAs, that can be transferred to infants and it plays on a critical role in biological functions such as immune regulation and development. However, the origin and functional importance of milk-derived miRNAs are still undetermined. This study applied RNA sequencing to explore the featured profiles of miRNA expression in colostrum and mature milk-originated exosomes from human, bovine, and caprine milk. These dietary exosome-derived miRNAs are highly conserved in human, bovine and caprine milk. Interestingly, abundant miRNAs expressed in human milk are similarly conserved across species. In addition, we confirmed that immune- related miRNAs (miR-30a-5p, miR-22-3p, and miR-26a) are commonly observed in the colostrum and mature milk of cows and caprines as well as humans. Our results provide new insights and resources for investigating the functionality of immune-associated miRNAs and evaluating physiological and biological condition in human, bovine and caprine milk as biomarkers.
Haeun CHO,Geonhee HAN,Kwang Yeon HWANG,Sun Hwa KIM,Yooso YANG 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
Exosomes are a type of extracellular vesicles with a diameter of 30 to 150 ㎚, and are secreted by multiple cell types. Exosomes can mediate cell-to-cell communication and modulate many physiological and pathological processes by carrying biomolecules such as nucleic acids, proteins and metabolites. In particular, bovine milk is a readily accessible source for mass production of exosome, and milk-exosomes can effectively deliver inflammatory and immunomodulatory active cargo through the gastrointestinal tract in a stable form. Here, we investigated the beneficial effects of bovine milk, especially colostrum-derived exosomes in a murine model of ulcerative colitis induced by dextran sodium sulfate (DSS). Our results showed that oral gavage of colostrum-derived exosomes can alleviate colitis symptoms such as abdominal pain, loss weight, diarrhea and rectal bleeding by regulating intestinal inflammatory immune responses. Collectively, our findings that bovine colostrum-derived exosomes with excellent structural and functional stability offer great potential as natural therapeutics for the recovery of colitis, may broaden the applications of milk consumption.