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Review
. 2022 Jun 10:13:896745.
doi: 10.3389/fimmu.2022.896745. eCollection 2022.

The Emerging Role of Plant-Derived Exosomes-Like Nanoparticles in Immune Regulation and Periodontitis Treatment

Zeyu Zhang  1   2 , Yang Yu  3 , Guanxiong Zhu  1   2 , Liting Zeng  1   2 , Shaofen Xu  1   2 , Haoyu Cheng  1   2 , Zhaoguang Ouyang  1   2 , Jianwei Chen  1   2 , Janak L Pathak  1 , Lihong Wu  1   2 , Lina Yu  1   2
Affiliations
Review

The Emerging Role of Plant-Derived Exosomes-Like Nanoparticles in Immune Regulation and Periodontitis Treatment

Zeyu Zhang et al. Front Immunol. .

Abstract

Periodontitis is an infectious oral disease, which leads to the destruction of periodontal tissues and tooth loss. Although the treatment of periodontitis has improved recently, the effective treatment of periodontitis and the periodontitis-affected periodontal tissues is still a challenge. Therefore, it is urgent to explore new therapeutic strategies for periodontitis. Natural products show anti-microbial, anti-inflammatory, anti-oxidant and bone protective effects to periodontitis and most of these natural products are safe and cost-effective. Among these, the plant-derived exosome-like nanoparticles (PELNs), a type of natural nanocarriers repleted with lipids, proteins, RNAs, and other active molecules, show the ability to enter mammalian cells and regulate cellular activities. Reports from the literature indicate the great potential of PELNs in the regulation of immune functions, inflammation, microbiome, and tissue regeneration. Moreover, PELNs can also be used as drug carriers to enhance drug stability and cellular uptake in vivo. Since regulation of immune function, inflammation, microbiome, and tissue regeneration are the key phenomena usually targeted during periodontitis treatment, the PELNs hold the promising potential for periodontitis treatment. This review summarizes the recent advances in PELNs-related research that are related to the treatment of periodontitis and regeneration of periodontitis-destructed tissues and the underlying mechanisms. We also discuss the existing challenges and prospects of the application of PELNs-based therapeutic approaches for periodontitis treatment.

Keywords: drug delivery systems; exosomes; extracellular vesicles; inflammation; oral tissue regeneration; periodontitis; plant-derived exosome-like nanoparticles.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Contents in PELNs. (A) Biogenesis and secretion: Plant cells can secrete PELNs via multivesicular bodies (MVB) and exocyst positive organelles (EXPO) (43, 44). (B) Size: PELNs range in size from 50 to 500 nm. (C) Components: Generally, PELNs contain fewer proteins and miRNAs than exosomes. (D) Targets: PELNs can be internalized in plant cells, mammalian cells, fungi, and bacteria (, –47). Created with BioRender.com.
Figure 2
Figure 2
Scheme of isolation and purification of PELNs by differential ultracentrifugation and sucrose gradient ultracentrifugation. Created with BioRender.com.
Figure 3
Figure 3
Scheme of PELNs internalization in mammalian cells and cargo release. Mammalian cells take up PELNs possibly through endocytosis and fusion. Cargoes in PELNs can be released into the cytoplasm in different ways, i.e., fusion with the lysosome, the disintegration of the early sorting endosome, and fusion with the endoplasmic reticulum, endosomal membrane and plasma membrane (22, 64). Created with BioRender.com.
Figure 4
Figure 4
Scheme of PELNs’ possible application in the treatment of periodontitis. PELNs show therapeutic potential for periodontitis via anti-inflammatory effect, microbiota modulation, and tissue regeneration. (A) Anti-inflammatory properties: PELNs inhibit pro-inflammatory protein expression in macrophages, such as IL-1β, IL-6, and TNF-α (55). (B) Modulate microbiota: PELNs inhibit pathogenic bacteria such as P. gingivalis through PA binding to HBP35 (19). PELNs protect probiotics through decay tRNA in probiotics (93). PELNs transform miRNA to microbiota, which has the potential to modulate oral microbiota. (C) Tissue regeneration: PELNs promote the proliferation of stem cells through activation of Wnt signals (30, 114). PENLs promote the production of collagen type I in epithelial cells (95).Created with BioRender.com.
Figure 5
Figure 5
Potential modifications of PELNs that can improve therapeutic efficacy against periodontitis. (A) PELNs can be loaded with specific miRNAs targeting immune cells and bacteria. (B) The amalgamation of liposomes with PELNs could augment the cargo loading capability of PELNs. (C) PELNs can be loaded with the drugs of interest to promote PDLSC functions. (D) PELNs fusion with a membrane rich in special receptors can improve target bacteria or cells in the periodontal region. (E) Coating of membrane rich in special receptors in PELNs can target immune cells. Created with BioRender.com.
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