Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery

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...
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Autor*in:	Jang, Hochung [verfasserIn] Kim, Hyosuk Kim, Eun Hye Han, Geonhee Jang, Yeongji Kim, Yelee Lee, Jong Won Shin, Sang Chul Kim, Eunice EunKyeong Kim, Sun Hwa Yang, Yoosoo

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Milk-derived exosome Surface modification Post-insertion Targeted delivery Antitumor effects

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: Biomaterials Research - London : BioMed Central, 2014, 27(2023), 1 vom: 29. Nov.
Übergeordnetes Werk:	volume:27 ; year:2023 ; number:1 ; day:29 ; month:11

Links:	Volltext

DOI / URN:	10.1186/s40824-023-00456-w

Katalog-ID:	SPR053914643

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520			\|a 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. Graphical Abstract
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allfields	10.1186/s40824-023-00456-w doi (DE-627)SPR053914643 (SPR)s40824-023-00456-w-e DE-627 ger DE-627 rakwb eng Jang, Hochung verfasserin aut Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 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. Graphical Abstract Milk-derived exosome (dpeaa)DE-He213 Surface modification (dpeaa)DE-He213 Post-insertion (dpeaa)DE-He213 Targeted delivery (dpeaa)DE-He213 Antitumor effects (dpeaa)DE-He213 Kim, Hyosuk aut Kim, Eun Hye aut Han, Geonhee aut Jang, Yeongji aut Kim, Yelee aut Lee, Jong Won aut Shin, Sang Chul aut Kim, Eunice EunKyeong aut Kim, Sun Hwa aut Yang, Yoosoo (orcid)0000-0003-3279-4362 aut Enthalten in Biomaterials Research London : BioMed Central, 2014 27(2023), 1 vom: 29. Nov. (DE-627)788845268 (DE-600)2775188-0 2055-7124 nnns volume:27 year:2023 number:1 day:29 month:11 https://dx.doi.org/10.1186/s40824-023-00456-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 27 2023 1 29 11
spelling	10.1186/s40824-023-00456-w doi (DE-627)SPR053914643 (SPR)s40824-023-00456-w-e DE-627 ger DE-627 rakwb eng Jang, Hochung verfasserin aut Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 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. Graphical Abstract Milk-derived exosome (dpeaa)DE-He213 Surface modification (dpeaa)DE-He213 Post-insertion (dpeaa)DE-He213 Targeted delivery (dpeaa)DE-He213 Antitumor effects (dpeaa)DE-He213 Kim, Hyosuk aut Kim, Eun Hye aut Han, Geonhee aut Jang, Yeongji aut Kim, Yelee aut Lee, Jong Won aut Shin, Sang Chul aut Kim, Eunice EunKyeong aut Kim, Sun Hwa aut Yang, Yoosoo (orcid)0000-0003-3279-4362 aut Enthalten in Biomaterials Research London : BioMed Central, 2014 27(2023), 1 vom: 29. Nov. (DE-627)788845268 (DE-600)2775188-0 2055-7124 nnns volume:27 year:2023 number:1 day:29 month:11 https://dx.doi.org/10.1186/s40824-023-00456-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 27 2023 1 29 11
allfields_unstemmed	10.1186/s40824-023-00456-w doi (DE-627)SPR053914643 (SPR)s40824-023-00456-w-e DE-627 ger DE-627 rakwb eng Jang, Hochung verfasserin aut Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 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. Graphical Abstract Milk-derived exosome (dpeaa)DE-He213 Surface modification (dpeaa)DE-He213 Post-insertion (dpeaa)DE-He213 Targeted delivery (dpeaa)DE-He213 Antitumor effects (dpeaa)DE-He213 Kim, Hyosuk aut Kim, Eun Hye aut Han, Geonhee aut Jang, Yeongji aut Kim, Yelee aut Lee, Jong Won aut Shin, Sang Chul aut Kim, Eunice EunKyeong aut Kim, Sun Hwa aut Yang, Yoosoo (orcid)0000-0003-3279-4362 aut Enthalten in Biomaterials Research London : BioMed Central, 2014 27(2023), 1 vom: 29. Nov. (DE-627)788845268 (DE-600)2775188-0 2055-7124 nnns volume:27 year:2023 number:1 day:29 month:11 https://dx.doi.org/10.1186/s40824-023-00456-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 27 2023 1 29 11
allfieldsGer	10.1186/s40824-023-00456-w doi (DE-627)SPR053914643 (SPR)s40824-023-00456-w-e DE-627 ger DE-627 rakwb eng Jang, Hochung verfasserin aut Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 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. Graphical Abstract Milk-derived exosome (dpeaa)DE-He213 Surface modification (dpeaa)DE-He213 Post-insertion (dpeaa)DE-He213 Targeted delivery (dpeaa)DE-He213 Antitumor effects (dpeaa)DE-He213 Kim, Hyosuk aut Kim, Eun Hye aut Han, Geonhee aut Jang, Yeongji aut Kim, Yelee aut Lee, Jong Won aut Shin, Sang Chul aut Kim, Eunice EunKyeong aut Kim, Sun Hwa aut Yang, Yoosoo (orcid)0000-0003-3279-4362 aut Enthalten in Biomaterials Research London : BioMed Central, 2014 27(2023), 1 vom: 29. Nov. (DE-627)788845268 (DE-600)2775188-0 2055-7124 nnns volume:27 year:2023 number:1 day:29 month:11 https://dx.doi.org/10.1186/s40824-023-00456-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 27 2023 1 29 11
allfieldsSound	10.1186/s40824-023-00456-w doi (DE-627)SPR053914643 (SPR)s40824-023-00456-w-e DE-627 ger DE-627 rakwb eng Jang, Hochung verfasserin aut Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 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. Graphical Abstract Milk-derived exosome (dpeaa)DE-He213 Surface modification (dpeaa)DE-He213 Post-insertion (dpeaa)DE-He213 Targeted delivery (dpeaa)DE-He213 Antitumor effects (dpeaa)DE-He213 Kim, Hyosuk aut Kim, Eun Hye aut Han, Geonhee aut Jang, Yeongji aut Kim, Yelee aut Lee, Jong Won aut Shin, Sang Chul aut Kim, Eunice EunKyeong aut Kim, Sun Hwa aut Yang, Yoosoo (orcid)0000-0003-3279-4362 aut Enthalten in Biomaterials Research London : BioMed Central, 2014 27(2023), 1 vom: 29. Nov. (DE-627)788845268 (DE-600)2775188-0 2055-7124 nnns volume:27 year:2023 number:1 day:29 month:11 https://dx.doi.org/10.1186/s40824-023-00456-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 27 2023 1 29 11
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authorswithroles_txt_mv	Jang, Hochung @@aut@@ Kim, Hyosuk @@aut@@ Kim, Eun Hye @@aut@@ Han, Geonhee @@aut@@ Jang, Yeongji @@aut@@ Kim, Yelee @@aut@@ Lee, Jong Won @@aut@@ Shin, Sang Chul @@aut@@ Kim, Eunice EunKyeong @@aut@@ Kim, Sun Hwa @@aut@@ Yang, Yoosoo @@aut@@
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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. 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author	Jang, Hochung
spellingShingle	Jang, Hochung misc Milk-derived exosome misc Surface modification misc Post-insertion misc Targeted delivery misc Antitumor effects Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery
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topic_title	Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery Milk-derived exosome (dpeaa)DE-He213 Surface modification (dpeaa)DE-He213 Post-insertion (dpeaa)DE-He213 Targeted delivery (dpeaa)DE-He213 Antitumor effects (dpeaa)DE-He213
topic	misc Milk-derived exosome misc Surface modification misc Post-insertion misc Targeted delivery misc Antitumor effects
topic_unstemmed	misc Milk-derived exosome misc Surface modification misc Post-insertion misc Targeted delivery misc Antitumor effects
topic_browse	misc Milk-derived exosome misc Surface modification misc Post-insertion misc Targeted delivery misc Antitumor effects
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title	Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery
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title_full	Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery
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author_browse	Jang, Hochung Kim, Hyosuk Kim, Eun Hye Han, Geonhee Jang, Yeongji Kim, Yelee Lee, Jong Won Shin, Sang Chul Kim, Eunice EunKyeong Kim, Sun Hwa Yang, Yoosoo
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title_sort	post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery
title_auth	Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery
abstract	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. Graphical Abstract © The Author(s) 2023
abstractGer	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. Graphical Abstract © The Author(s) 2023
abstract_unstemmed	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. Graphical Abstract © The Author(s) 2023
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title_short	Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery
url	https://dx.doi.org/10.1186/s40824-023-00456-w
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author2	Kim, Hyosuk Kim, Eun Hye Han, Geonhee Jang, Yeongji Kim, Yelee Lee, Jong Won Shin, Sang Chul Kim, Eunice EunKyeong Kim, Sun Hwa Yang, Yoosoo
author2Str	Kim, Hyosuk Kim, Eun Hye Han, Geonhee Jang, Yeongji Kim, Yelee Lee, Jong Won Shin, Sang Chul Kim, Eunice EunKyeong Kim, Sun Hwa Yang, Yoosoo
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up_date	2024-07-03T22:52:59.506Z
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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. Graphical Abstract</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Milk-derived exosome</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Surface modification</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Post-insertion</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Targeted delivery</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Antitumor effects</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kim, Hyosuk</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kim, Eun Hye</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Han, Geonhee</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Jang, Yeongji</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kim, Yelee</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lee, Jong Won</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Shin, Sang Chul</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kim, Eunice EunKyeong</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kim, Sun Hwa</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yang, Yoosoo</subfield><subfield code="0">(orcid)0000-0003-3279-4362</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Biomaterials Research</subfield><subfield code="d">London : BioMed Central, 2014</subfield><subfield code="g">27(2023), 1 vom: 29. 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Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery

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