Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle vesicles.Exosomes have proven to be excellent nanocarriers for carrying lipids,pr...Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle vesicles.Exosomes have proven to be excellent nanocarriers for carrying lipids,proteins,mRNAs,non-coding RNAs,and DNAs,and disseminating long-distance intercellular communications in various biological processes.Among various cell-line or biological fluid derived exosomes,milk exosomes are abundant in nature and exhibit many nanocarrier characteristics favorable for theranostic applications.To be an effective delivery carrier for their clinical translation,exosomes must inbuilt loading,release,targeting,and imaging/tracking characteristics.Considering the unmet gaps of milk exosomes in theranostic technology it is essential to focus the current review on drug delivery and imaging applications.This review delineates the efficiency of exosomes to load therapeutic or imaging agents and their successful delivery approaches.It is emphasized on possible modifications of exosomes towards increasing the stability and delivery of agents.This article also summarizes the specific applications and the process of developing milk exosomes as a future pharmaceutical drug delivery vehicle.展开更多
Milk-derived exosomes are widely used for diagnosis,delivery,imaging,and theranostic applications.Near-Infrared(NIR)based fluorescence bioimaging is an attractive and safer technique that is used for clinical applicat...Milk-derived exosomes are widely used for diagnosis,delivery,imaging,and theranostic applications.Near-Infrared(NIR)based fluorescence bioimaging is an attractive and safer technique that is used for clinical applications.However,almost all NIR imaging agents tend to have poor photostability,short half-life,nonspecific protein binding,and concentrationdependent aggregation(s).Therefore,there is an unmet clinical need to develop newer and safer modalities to package and deliver NIR imaging agents.Bovine milk exosomes are natural,biocompatible,safe,and efficient nanocarriers that facilitate the delivery of micro-and macromolecules.Herein,we developed an exosome-based NIR dye loaded nanoimaging formulation that offers improved solubility and photostability of NIR dye.Following the acetic acid based extracellular vesicle(EV)treatment method,we extracted the bovine milk exosomes from a variety of pasteurized grade milk.The EVs were screened for their physicochemical properties such as particle size and concentration and zeta potential.The stability of these exosomes was also determined under different conditions,including storage temperatures,pH,and salt concentrations.Next,indocyanine green,a model NIR dye was loaded into these exosomes(Exo-Glow)via a sonication method and further assessed for their improved fluorescence intensity and photostability using an IVIS imaging system.Initial screening suggested that size of the selected bovine milk exosomes was∼100−135 nm with an average particle concentration of 5.8×10^(2)particles/mL.Exo-Glow further demonstrated higher fluorescence intensity in cancer cells and tissues when compared to free dye.These results showed that Exo-Glow has the potential to serve as a safer NIR imaging tool for cancer cells/tissues.展开更多
基金support from Department of Immunology and Microbiology,School of Medicine,University of Texas Rio Grande Valley to MMY,MJ,and SCC.This work is partially supported by NIH grants(R01 CA210192,R01 CA206069 and R01 CA204552).
文摘Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle vesicles.Exosomes have proven to be excellent nanocarriers for carrying lipids,proteins,mRNAs,non-coding RNAs,and DNAs,and disseminating long-distance intercellular communications in various biological processes.Among various cell-line or biological fluid derived exosomes,milk exosomes are abundant in nature and exhibit many nanocarrier characteristics favorable for theranostic applications.To be an effective delivery carrier for their clinical translation,exosomes must inbuilt loading,release,targeting,and imaging/tracking characteristics.Considering the unmet gaps of milk exosomes in theranostic technology it is essential to focus the current review on drug delivery and imaging applications.This review delineates the efficiency of exosomes to load therapeutic or imaging agents and their successful delivery approaches.It is emphasized on possible modifications of exosomes towards increasing the stability and delivery of agents.This article also summarizes the specific applications and the process of developing milk exosomes as a future pharmaceutical drug delivery vehicle.
基金supported by Start-up from Division of Immunology and Microbiology,Medicine and Oncology ISU,School of Medicine,University of Texas Rio Grande Valley and NIH grants(SC1GM139727,R01 CA210192,and R01 CA206069)This research work utilized equipment and services of Integrated Cancer Research Center funded by CPRIT(RP210180 and RP230419)and UT System Star Award.
文摘Milk-derived exosomes are widely used for diagnosis,delivery,imaging,and theranostic applications.Near-Infrared(NIR)based fluorescence bioimaging is an attractive and safer technique that is used for clinical applications.However,almost all NIR imaging agents tend to have poor photostability,short half-life,nonspecific protein binding,and concentrationdependent aggregation(s).Therefore,there is an unmet clinical need to develop newer and safer modalities to package and deliver NIR imaging agents.Bovine milk exosomes are natural,biocompatible,safe,and efficient nanocarriers that facilitate the delivery of micro-and macromolecules.Herein,we developed an exosome-based NIR dye loaded nanoimaging formulation that offers improved solubility and photostability of NIR dye.Following the acetic acid based extracellular vesicle(EV)treatment method,we extracted the bovine milk exosomes from a variety of pasteurized grade milk.The EVs were screened for their physicochemical properties such as particle size and concentration and zeta potential.The stability of these exosomes was also determined under different conditions,including storage temperatures,pH,and salt concentrations.Next,indocyanine green,a model NIR dye was loaded into these exosomes(Exo-Glow)via a sonication method and further assessed for their improved fluorescence intensity and photostability using an IVIS imaging system.Initial screening suggested that size of the selected bovine milk exosomes was∼100−135 nm with an average particle concentration of 5.8×10^(2)particles/mL.Exo-Glow further demonstrated higher fluorescence intensity in cancer cells and tissues when compared to free dye.These results showed that Exo-Glow has the potential to serve as a safer NIR imaging tool for cancer cells/tissues.
