Plant Exosome-like Nanovesicles: Emerging Therapeutics and Drug Delivery Nanoplatforms

Abstract

Plant exosome-like nanovesicles, being innately replete with bioactive lipids, proteins, RNA, and other pharmacologically active molecules, offer unique morphological and compositional characteristics as natural nanocarriers. Furthermore, their compelling physicochemical traits underpin their modulative role in physiological processes, all of which have fostered the concept that these nanovesicles may be highly proficient in the development of next-generation biotherapeutic and drug delivery nanoplatforms to meet the ever-stringent demands of current clinical challenges. This review systemically deals with various facets of plant exosome-like nanovesicles ranging from their origin and isolation to identification of morphological composition, biological functions, and cargo-loading mechanisms. Efforts are made to encompass their biotherapeutic roles by elucidating their immunological modulating, anti-tumor, regenerative, and anti-inflammatory roles. We also shed light on re-engineering these nanovesicles into robust, innocuous, and non-immunogenic nanovectors for drug delivery through multiple stringent biological hindrances to various targeted organs such as intestine and brain. Finally, recent advances centered around plant exosome-like nanovesicles along with new insights into transdermal, transmembrane and targeting mechanisms of these vesicles are also elucidated. We expect that the continuing development of plant exosome-like nanovesicle-based therapeutic and delivery nanoplatforms will promote their clinical applications.

Keywords: drug delivery nanoplatforms; nanotherapeutics; plant exosome-like nanovesicles.

Graphical abstract

Figure 1

Biogenesis of PELNVs and Their Functions in Plant Physiology PELNVs are formed by inward budding of MVBs with the content in similar orientation as in the plasmalemma, and fusion of MVBs with plasmalemma permits the release of PELNVs.

Figure 2

Isolation and Preparation of PELNVs PELNVs could be isolated and prepared by series of centrifugations, including ultracentrifugation and sucrose gradient ultracentrifugation.

Figure 3

Re-engineering Method for PELNVs and Drug Loading Procedure The Bligh and Dyer extraction method is used for nanolipid extraction from PELNVs to re-engineer them into nanovectors. The drug loading procedure comprises the sonication technique for drug loading onto re-engineered nanovectors and an incubation method for drug loading onto pristine PELNVs.

Figure 4

Overview of Biological Functions of PELNVs from a Variety of Plant Sources and Their Translation into Therapeutic Applications (A) Summary of the biological functions of PELNVs derived from plants. (B) Elucidation of therapeutic mechanisms of PELNVs in immunological modulation, tissue repair, and intestinal transporters modulation.

Figure 5

Mechanism of PELNV miRNAs Regulating the Inter-kingdom Communication between Gut Microbiota and the Host Immune System PELNV mRNA-mediated targeting of the LGG monooxygenase ycnE increase the yields of indole-3-carboxaldehyde (I3A), which leads to inducing the production of IL-22. IL-22 can improve the barrier function and ameliorate colitis in mice.

Figure 6

Schematic Illustration of Transdermal Delivery of PELNVs PELNVs could penetrate the stratum corneum though three pathways: transcellular routes, intercellular routes, and appendageal routes.

Figure 7

Modification of PELNVs for Targeted Drug Delivery (A–D) Targeted drug delivery applications of (A) pristine PELNVs and (B) PELNV re-engineered nanovectors, with further elucidation of surface functionalization of pristine PELNVs, and (C and D) surface modification of re-engineered nanovectors for achieving cargo loading and targeted delivery.

Figure 8

Elucidation of Multiple Pathways of Cellular Internalization/Uptake of PELNVs after Introduction into the Subject Facilitated diffusion, endocytosis, and direct fusion are shown.