Jang, Hochung HYOSUK KIM Kim, Eun Hye Han, Geonhee Yeongji, Jang Kim, Yelee Lee, Jong Won Shin, Sang Chul Kim, Eunice Eun Kyeong Kim, Sun Hwa Yang, Yoosoo 2024-01-12T06:32:08Z 2024-01-12T06:32:08Z 2023-11-30 2023-11 1226-4601 https://pubs.kist.re.kr/handle/201004/79734 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 post-insertion method was examined comprehensively. Exosomes were engineered from bovine milk (mExo) with surface-tunable 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. English The Korean Society for Biomaterials | BioMed Central Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery Article 10.1186/s40824-023-00456-w 1 Biomaterials Research, v.27, no.1, pp.2842 - 2858 Biomaterials Research 27 1 2842 2858 Y scie scopus kci ART003026045 001110711000001 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article COLORECTAL-CANCER ANCHORING LIPIDS FOLATE RECEPTOR DOXORUBICIN RNA INSERTION Milk-derived exosome Surface modification Post-insertion Targeted delivery Antitumor effects