Encapsulation and assessment of therapeutic cargo in engineered exosomes: a systematic review

Abstract

Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies. Graphical Abstract

Dual anti-angiogenic and anti-inflammatory action of tRNA-Cys-5-0007 in ocular vascular disease

“…They have excellent stability with a long half-life in the bloodstream and can be easily taken up by cells [ 55 , 56 ]. Additionally, their nanoscale size allows them to traverse blood-ocular barriers effectively [ 57 ]. Exosomes can be administered through vitreous cavity to reach the inner and outer retinal layers, or through peribulbar or retrobulbar regions across the ocular walls, providing a safer and more efficient drug delivery method compared to systemic intravenous injection [ 55 ].…”

Neural Stem Cell-Derived Small Extracellular Vesicles: key Players in Ischemic Stroke Therapy – A Comprehensive Literature Review

“…As research progresses, the limitations of utilizing natural sEVs for treating ischemic stroke are becoming increasingly evident, specifically in their inadequate targeting capabilities and content loading. 101 , 102 Several approaches have been devised to rectify these limitations and enhance the targeting, stability, and loading capacity of NSC-sEVs. These modifications together fall under the category of engineered NSC-sEVs.…”

Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery

“…This makes them a good candidate for oral drug delivery. Numerous studies have investigated the loading techniques of plant-derived EVs with nucleic acids and have shown that EVs can protect loaded nucleic acids from enzymatic degradation and deliver them in an intact and functional form [ 113 , 114 ]. Techniques used for plant EV loading include electroporation, which causes transient pore formation and allows nucleic acid entrance into EVs; sonication of EVs in the presence of nucleic acids to alter membrane structures; passive nucleic acid internalization in the presence of appropriate salt, pH, and temperature conditions; and mechanically (extrusion techniques) or chemically increased membrane permeability to allow nucleic acids entrance.…”

“…Techniques used for plant EV loading include electroporation, which causes transient pore formation and allows nucleic acid entrance into EVs; sonication of EVs in the presence of nucleic acids to alter membrane structures; passive nucleic acid internalization in the presence of appropriate salt, pH, and temperature conditions; and mechanically (extrusion techniques) or chemically increased membrane permeability to allow nucleic acids entrance. The efficacy of these techniques varies depending on the EV source and the nucleic acid type [ 113 ].…”