Harnessing Mammalian- and Plant-Derived Exosomes for Drug Delivery: A Comparative Review

Abstract

Exosomes, nanoscale vesicles involved in intercellular communication, have garnered significant attention for their potential in drug delivery and therapeutic applications. This review provides a comparative analysis of mammalian-derived exosomes, particularly milk-derived exosomes, and plant-derived exosome-like nanoparticles (PDENs). It explores their biogenesis, bioactivities, and functional similarities, including their roles in cellular communication, immune modulation, and disease therapy. While milk-derived exosomes exhibit promising biocompatibility and stability for targeted delivery, PDENs offer distinct advantages, such as scalability and inherent bioactivities, derived from their plant sources. Despite similarities in their structure and cargo, PDENs differ in lipid composition and protein profiles, reflecting plant-specific functions. Emerging research highlights the therapeutic potential of PDENs in managing inflammation, oxidative stress, and other diseases, emphasizing their utility as functional food components and nanocarriers. However, challenges related to their chemical stability and large-scale production require further investigation. This review underscores the need for advanced studies to fully harness the potential of these natural nanocarriers in drug-delivery systems and therapeutic interventions.

Keywords: drug delivery; exosomes; mammalian-derived extracellular vesicles; plant-based exosomes.

Figure 3

Schematic representation of plant-derived exosome-like nanoparticles (PDENs) and their formation pathway. Formation of PDENs may go through the multivesicular bodies (MVBs) pathway. The process involves inward budding of plasma membrane, resulting in the formation of early endosomes that mature and interact with the trans-Golgi network apparatus. Consequently, this leads to the formation of MVBs. MVBs fuse with the cytoplasmic membrane and release intraluminal vesicles (ILVs) into the outer environment. Released ILVs are classified as PDENs [73].

Figure 1

Schematic representation of milk-derived exosomes. Milk-derived exosomes are lipid bilayer-bound nanovesicles secreted into milk, containing bioactive cargos such as proteins (tetraspanins, heat shock proteins), lipids (cholesterol, sphingomyelin, phosphatidylserine), and nucleic acids (miRNAs, mRNAs). Their structure facilitates biostability and interspecies compatibility, protecting encapsulated molecules from enzymatic degradation. Functionally, they participate in cellular communication, immune modulation, and serve as efficient vehicles for delivering therapeutic agents like chemotherapeutics, siRNAs, and antioxidants across biological barriers (e.g., blood-brain barrier). Their high biocompatibility and bioactivity make them promising platforms for drug delivery and regenerative medicine.

Figure 2

Promising potential biomedical applications of milk-derived exosomes.

Figure 4

Promising potential biomedical applications of PDENs.