Case Report - Volume 2 - Issue 4
Plant Exosome-like Nanovesicles: A Nanoplatform for the Drug Delivery
Krishnananda P Ingle1; Gholamreza Abdi2; Marjan Assefi3*; Sohila Nankali4; Nadeem Kizilbash5
1Koneru Lakshmaiah University, College of Agriculture, Vaddeswaram, Guntur, P.O. Box 522502, Andhra Pradesh, India.
2Department of Biotechnology, Persian Gulf Research Institute, Persian Gulf University, Bushehr 75169, Iran.
3University of North Carolina at Greensboro, Greensboro, NC 27403, USA.
4University of North Central, Sandiego, USA.
5Department of Chemistry, Faculty of Physcal Sciences, Islamabad.
Received Date : June 20, 2022
Accepted Date : July 27, 2022
Published Date: Aug 17, 2022
Copyright:© Marjan Assef 2022
*Corresponding Author : Marjan Assefi, University of North Carolina at Greensboro, Greensboro, NC 27403, USA
Email: massefi@aggies.ncat.edu
DOI: Doi.org/10.55920/2771-019X/1217
Abstract
These days, with the overall spread of various tumors; there is a pressing need in new treatment strategies and prescriptions. With the appearance of medication conveyance strategies, we have gone to another time of treatment. Here, we go to the way that the Plant Exosome-like Nanovesicles will open new open new ways to the logical tests. Various strategies in nano bioelectronics and the significance of Nano science and Nano designing have been examined. Plant Exosome-like Nanovesicles are utilized in drug conveyance framework at nano bio electronic office. It has polar and nonpolar district. Medications will embed into the Plant Exosome-like Nanovesicles. In this paper, they will determine what Plant Exosome-like Nanovesicles are, various procedures to enter Plant Exosome-like Nanovesicles to the objective cells, how it very well may be made, and cooperation’s among Plant Exosome-like Nanovesicles and cell layer. Also, the Preparation of PELNVS and Re-Engineering of PELNVs were discussed.
Keywords: Drug Delivery; Exosome-like; Plant; Nanovesicles.
Introduction
Exosome
Exosomes are biological nanovesicles (40–150 nm), are secreted by plant cells and transmits signals among the cells and organisms (1). Plant Exosome like nanovesicles (PELNVs) are similar to the mammalian Exosome like Nano vesicles (ELNVs) (2). PELNVs are experimentally harmless and eco-friendly vigorous and viable nano-carriers for modern medicine (3). Plant-derived exosome-like nanoparticles (PELNVs) are effective to treat the diseases. PELNVs are low cytotoxic and show good biocompatibility compare with synthesized nanoparticles which are linked with complications like immunogenicity, cytotoxicity (4). PELNVs also having the capacity to target specific tissues like tumour cells through endocytosis mechanisms. PELNVs can be use drug therapies and reducing the off-target effects. PELNVs are not only limited to plants cells crosstalk, it also insights inter-kingdom communications (5). Researchers are mainly focused on plant nanovesicles in host-pathogen-interactions [15–17] and health-beneficial effects [18–24]. Another approach to use the advantageous properties of plant nanovesicles can be to foster the use of these small non-coding RNA (sRNA)-containing vehicles as bio-compatible and sustainable plant protection agents [25].
This chapter comprehensively describes the plant exosome-like nanovesicles morphological composition and biogenesis of exosomes, physiological functions, Re-engineering of PELNVs and Recent advances in PELNVs along with new insights into development of therapeutic and their clinical applications.
Composition and Biogenesis of Exosomes
Plant exosome vesicles are biogenesis due to various stresses like biotic and abiotic [6]. Qianli et al (2007) reported on barley leaves intravacuolar Multivesicular bodies (MVBs) are produced in the cytoplasm. Barley MVBs contact with cell wall-associated paramural bodies (PMBs) enclosing vesicles, in which membranous or vesicular structures that are placed between the plasma membrane and curved cell wall regions of plant and fungal cells, possibly resulting in the obstruction of growing papillae (7). As like mammalian cell-derived exosomes (MDEs), Endosomal sorting complex required for transport complexes (ESCRT) viz., ESCRT-0, I, II, and III are involved in the development of PELNVs in plants [8]. In the biogenesis exosome is trafficking to the ESCRT-I and ESCRT-II complexes through the ubiquitin- binding proteins, then the ESCRT-II complex stimulates and recruits ESCRT-III. However, the PELNVs biogenesis is differing from the MDEs biogenesis. However the biogenesis of PELNVs reported, strong demonstration is needed for the PELNVs biogenesis [9]. There is a need to development of an advance approaches for effective and efficient drug delivery to treat the diseases. Among the approaches PELNVs-based strategy could be a latent approach in the treatment of diseases. Generally, PELNVs, are natural nanoparticles secreted in different plants like grapes [10], grapefruits [11], ginger [12], lemon [13], broccoli [14], coconut [15], carrot [16], and apple [17], has various advantages. PELNVs has been involved in various activities on plant physiological and metabolic processes.
Physiological actions of PELNVs
PELNVs has different components, and intrinsic molecules an it clearly involved in various patterns of signalling regulation pathways. PELNVs constituents are naturally evolved in plant cells, hence it has good biocompatibility and low cytotoxicity. PELNVs are naturally contains therapeutic materials as like MDEs, which can be transferred to the specific target cells. It also has the properties like morphology equal size distribution, density and surface electric charge [18, 19]. Liposomes and artificially synthesized nanoparticles are using in Conventional Drug Delivery System. But these artificial nanoparticles has various limitations like low biocompatibility, toxicity, poor targeting efficiency, and short retention time in the circulatory system of body [20,21]. PELNVs are having high rigidity, suitable morphology and stability, it also can integrate with drugs and to target the specific cells or tissues in the body [22]. The tissue specificity of PELNVs is decided by lipids and proteins orientation, ability to change the gene expressions, hydrophobic drugs transfer, and escape from the immunity. Plant defence mechanism and in the developmental processes PELNVs plays important role [27, 28]. Plant exosome-like nanovesicles (PELNVs), being innately deploy with bioactive compounds like lipids, proteins, RNA, and other pharmacologically active molecules, offer unique morphological and compositional characteristics as natural nanocarriers. It also convincing physicochemical traits support their modulative role in physiological processes, all of which have adopted the concept that these nanovesicles may be highly proficient in the development of next-generation biotherapeutic and drug delivery nanoplatforms to meet the current stringent demands of current clinical challenges.
1. a) Preparation of PELNVS
One of the major advantages of PELNVs is it can prepare from edible plants, which allows abundant quantity preparation. The overlapped size range and rather indistinguishable morphological similarities necessitate the current efforts in designing a feasible isolation method of ELNVs from the masses of the subpopulation of extracellular vesicles (EVs). In this consideration, the differential ultracentrifugation (UC) technique is commonly used and has acquired the benchmark status in isolation and purification of ELNVs owing to its ease of use and inexpensiveness (23,24). The preparation technique mainly depends on the size and density variations of nano particles (25). Plant extract through a continuous centrifugation with gradually increasing the speed and subsequent cycles, gradually increase the centrifugation speed and longer duration than the previous cycle to get the higher density particles. In the subsequent step, collect the supernatant and subjected to high speed centrifugation (100,000 ×g) to regain the pellet, which is subsequently resuspend and wash with phosphate-buffer (26). PELNVs pave a way to understand the communications among the cells and development of nano vesicles to target specific drug delivery.
- b) Re-Engineering of PELNVs
Re-engineering of PELNVs is major focus on to prepare uniform-sized PELNVs because they vary in size (50 to 500nm). For efficient drug loading and delivery is one major criterion, but it is not possible with original form of PELNVs. So, it is essential to formulate uniform-sized nanoparticles with competent drug loading (29). For the re-engineering of PELNVs as drug delivery nanoplatforms, scientists have successfully adopted the Bligh and Dyer technique to extract nano-lipids from PELNVs, In this technique extracted nano-lipids are processed through a 200-nm liposome extruder, which eventually reform them into a uniform-size (30). PELNVs inherently express lipids and phosphatidic acid (PA) that naturally promote adhesion to a particular cell, and natural biodistribution (31). It also has tailored their surface, which can expand the scope of desired target specificity [32] . Specific functionalizing PELNVs-based nanoplatforms can help in specific cancer treatment.
Morphological Characterization
To illustrate ultrastructure analysis of the subcellular status of PELNVs, Transmission electron microscopy (TEM) and atomic force microscopy (AFM) is used [33, 34, 35]. By measuring resolution in fractions of nanometers, AFM proves its superiority to traditional optical microscopy [36, 37]. Dynamic light scattering (DLS), also known as quasi-elastic light scattering, photon correlation spectroscopy, can be used to determine the size and zeta potential of scattered PELNVs [35]. DLS is the benchmark approach in the evaluation of size distribution of suspension particles in numerous scientific disciplines since it is non-intrusive and ultra-sensitive, requiring only a small sample volume to calculate accurate and precise size [38-40]. Furthermore, researchers are increasingly using nanoparticle tracking analysis (NTA) to quantify the amount of ELNVs in a sample container and characterise their size distribution.
Biochemical Characterization
In terms of protein, lipid, and RNA concentration, PELNVs' chemical composition profiles differ significantly from those of mammalian-derived ELNVs [35]. Lipid, nucleic acid, and protein compositional analyses of PELNVs are valued as essential characterization criteria for PELNV quality control [41, 42]. Plant and mammalian cell-derived ELNVs use the same chemical component characterisation methodologies. Immunoblotting of certain proteins is the most extensively used method for confirming the origin of ELNVs. For detailed study of the components of PELNVs, ELISA, sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis (PAGE), [43] liquid chromatography-tandem massspectroscopy, [44, 45] a microfluidic electrophoresis analyzer, and high-throughput small RNA sequencing have been established [46, 47]. Protein analysis commonly uses colorimetric tests such as bicinchoninic acid (BCA), fluorimetric assays, SDS-PAGE, and western blotting [48]. Raman spectroscopy is another advanced molecular characterisation technique that shows the chemical structure of PELNVs by producing a laser beam. They contain a specific range of biomolecules, such as peptides and nucleic acids [49]. Furthermore, for RNA content investigation of PELNVs, microarray analysis, digital droplet PCR, and next-generation sequencing approaches have been devised [50]. A sulfophospho-vanillin test and total reflection Fourier transform infrared spectroscopy [51] are the most often utilised procedures for lipidomic characterization of PELNVs.
References
- Colombo M, Raposo G and Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 2014; 30: 255-289.
- Woith E, Guerriero G, Hausman JF, Renaut J, Leclercq CC, et al. Plant Extracellular Vesicles and Nanovesicles: Focus on Secondary Metabolites, Proteins and Lipids with Perspectives on Their Potential and Sources. Int. J. Mol. Sci. 2021; 22: 3719. https://doi.org/10.3390/ijms22073719
- Dad et al. Plant Exosome-like Nanovesicles: Emerging Therapeutics and Drug Delivery Nanoplatforms, Molecular Therapy, 2020. https://doi.org/10.1016/j.ymthe.2020.11.030
- De Jong WH, and Borm PJ. Drug delivery and nanoparticles: applications and hazards. Int. J. Nanomedicine, 2008; 3: 133-149.
- Liang H, Zhang S, Fu Z, Wang Y, Wang N, Liu Y, et al. Effective detection and quantification of dietetically absorbed plant microRNAs in human plasma. J. Nutr. Biochem. 2015; 26: 505-512.
- An Q, Huckelhoven R, Kogel KH, van Bel AJ . Multivesicular bodies participate in a cell wall-associated defence response in barley leaves attacked by the pathogenic powdery mildew fungus. Cell Microbiol 2006; 8(6): 1009-19.
- Qianli AJVB, Hückelhoven R. Do plant cells secrete exosomes derived from multivesicular bodies? Plant Signal Behav, 2007; 2(1): 4-7.
- Gao C, Zhuang X, Shen J, Jiang L. Plant ESCRT complexes: moving beyond endosomal sorting. Trends Plant Sci, 2017; 22(11): 986-98.
- Marchant R, Robards AWR. Membrane systems associated with the plasmalemma of plant cells. Ann Bot, 1968; 32: 457-71.
- Ju S, Mu J, Dokland T, Zhuang X, Wang Q, Jiang H, et al. Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis. Mol Ther, 2013; 21(7): 1345-57.
- Wang B, Zhuang X, Deng ZB, Jiang H, Mu J, Wang Q, et al. Targeted drug delivery to intestinal macrophages by bioactive nanovesicles released from grapefruit. Mol Ther, 2014; 22(3): 522-34.
- Brahmbhatt M, Gundala SR, Asif G, Shamsi SA, Aneja R. Ginger phytochemicals exhibit synergy to inhibit prostate cancer cell proliferation. Nutr Cancer, 2013; 65(2): 263-72.
- Raimondo S, Naselli F, Fontana S, Monteleone F, Lo Dico A, Saieva L, et al. Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death. Oncotarget, 2015; 6(23): 19514-27.
- Deng Z, Rong Y, Teng Y, Mu J, Zhuang X, Tseng M, et al. Broccoli-derived nanoparticle inhibits mouse colitis by activating dendritic cell AMP-activated protein kinase. Mol Ther, 2017; 25(7): 1641-54.
- Yu S, Zhao Z, Xu X, Li M, Li P. Characterization of three different types of extracellular vesicles and their impact on bacterial growth. Food Chem, 2019; 272: 372-8.
- Mu J, Zhuang X, Wang Q, Jiang H, Deng ZB, Wang B, et al. Interspecies communication between plant and mouse gut host cells through edible plant derived exosome-like nanoparticles. Mol Nutr Food Res, 2014; 58(7): 1561-73.
- Fujita D, Arai T, Komori H, Shirasaki Y, Wakayama T, Nakanishi T, et al. Apple-derived nanoparticles modulate expression of organic-anion-transporting polypeptide (OATP) 2B1 in caco-2 cells. Mol Pharm, 2018; 15(12): 5772-80.
- Raimondo S, Naselli F, Fontana S, Monteleone F, Lo Dico A, Saieva L, et al. Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death. Oncotarget, 2015; 6(23): 19514-27.
- Deng Z, Rong Y, Teng Y, Mu J, Zhuang X, Tseng M, et al. Broccoli-derived nanoparticle inhibits mouse colitis by activating dendritic cell AMP-activated protein kinase. Mol Ther, 2017; 25(7): 1641-54.
- Buchman J, Hudson-Smith N, Landy K, Haynes C. Understanding nanoparticle toxicity mechanisms to inform redesign strategies to reduce environmental impact. Acc Chem Res, 2019; 52(6): 1632-42.
- Bahadar H, Maqbool F, Niaz K, Abdollahi M. Toxicity of nanoparticles and an overview of current experimental models. Iran Biomed J, 2016; 20(1): 1-11.
- Teng Y, Ren Y, Sayed M, Hu X, Lei C, Kumar A, et al. Plant-derived exosomal microRNAs shape the gut microbiota. Cell Host Microbe, 2018; 24(5): 637-52.
- Pérez-Bermúdez P, Blesa J, Soriano JM and Marcilla A. Extracellular vesicles in food: experimental evidence of their secretion in grape fruits. Eur. J. Pharm. Sci. 2017; 98: 40-50.
- Pocsfalvi G, Turiák L, Ambrosone A, Del Gaudio P, Puska G, Fiume I, Silvestre T and Vékey K. Protein biocargo of citrus fruit-derived vesicles reveals heterogeneous transport and extracellular vesicle populations. J. Plant Physiol. 2018; 229: 111-121.
- Li P, Kaslan M, Lee SH, Yao J and Gao Z. Progress in exosome isolation techniques. Theranostics, 2017; 7: 789-804.
- Regente M, Pinedo M, San Clemente H, Balliau T, Jamet E and de la Canal L. Plant extracellular vesicles are incorporated by a fungal pathogen and inhibit its growth. J. Exp. Bot. 2017; 68: 5485-5495.
- Hansen LL and Nielsen ME. Plant exosomes: using an unconventional exit to prevent pathogen entry? J. Exp. Bot. 2017; 69: 59-68.
- Cai Q, Qiao L, Wang M, He B, Lin FM, Palmquist J, et al. Plants send small RNAs in extracellular vesicles to fungal pathogen to silence virulence genes. Science, 2018; 360: 1126-1129.
- Van der Meel R, Fens MH, Vader P, van Solinge WW, Eniola-Adefeso O, and Schiffelers RM. Extracellular vesicles as drug delivery systems: lessons from the liposome field. J. Control. Release, 2014; 195: 72-85.
- Loureiro JA, Andrade S, Duarte A, Neves AR, Queiroz JF, Nunes C, et al. Resveratrol and grape extract-loaded solid lipid nanoparticles for the treatment of Alzheimer’s disease. Molecules, 2017; 22: 277.
- Wang X, Devaiah SP, Zhang W, and Welti R. Signaling functions of phosphatidic acid. Prog. Lipid Res. 2006; 45: 250-278.
- Liu C, and Su C. Design strategies and application progress of therapeutic exosomes. Theranostics, 2019; 9: 1015-1028.
- Chevillet JR, Kang Q, Ruf IK, Briggs HA, Vojtech LN, Hughes SM, et al. Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proc. Natl. Acad. Sci. USA. 2014; 111: 14888-14893.
- Van der Pol E, Hoekstra AG, Sturk A, Otto C, van Leeuwen TG, and Nieuwland R. Optical and non-optical methods for detection and character ization of microparticles and exosomes. J. Thromb. Haemost. 2010; 8: 2596-2607.
- Mu J, Zhuang X, Wang Q, Jiang H, Deng ZB, Wang B, et al. Interspecies communication between plant and mouse gut host cells through edible plant derived exosome-like nanoparticles. Mol. Nutr. Food Res. 2014; 58: 1561-1573.
- Palanisamy V, Sharma S, Deshpande A, Zhou H, Gimzewski J, and Wong DT. Nanostructural and transcriptomic analyses of human saliva derived exo somes. PLoS ONE, 2010; 5: e8577.
- Sharma S, Rasool HI, Palanisamy V, Mathisen C, Schmidt M, Wong DT and Gimzewski JK. Structural-mechanical characterization of nanoparticle exo somes in human saliva, using correlative AFM, FESEM, and force spectroscopy. ACS Nano, 2010; 4: 1921-1926.
- Zhang MZ, Li C, Fang BY, Yao MH, Ren QQ, Zhang L, and Zhao YD. High transfection efficiency of quantum dot-antisense oligonucleotide nanoparticles in cancer cells through dual-receptor synergistic targeting. Nanotechnology, 2014; 25: 255102.
- Zhang MZ, Yu RN, Chen J, Ma ZY and Zhao YD. Targeted quantum dots fluorescence probes functionalized with aptamer and peptide for transferrin receptor on tumor cells. Nanotechnology, 2012; 23: 485104.
- Zhang MZ, Yu Y, Yu RN, Wan M, Zhang RY and Zhao YD. Tracking the down-regulation of folate receptor-a in cancer cells through target specific delivery of quantum dots coupled with antisense oligonucleotide and targeted peptide. Small, 2013; 9: 4183-4193
- Stanly C, Fiume I, Capasso G and Pocsfalvi G. Isolation of exosome-like vesicles from plants by ultracentrifugation on sucrose/deuterium oxide (D2O) den sity cushions. Methods Mol. Biol. 2016; 1459: 259-269.
- Woith E, and Melzig MF. Extracellular vesicles from fresh and dried plants—simultaneous purification and visualization using gel electrophoresis. Int. J. Mol. Sci. 2019; 20: 357.
- Lamparski HG, Metha-Damani A, Yao JY, Patel S, Hsu DH, Ruegg C and Le Pecq JB. Production and characterization of clinical grade exosomes derived from dendritic cells. J. Immunol. Methods, 2002; 270: 211–226.
- Andriolo G, Provasi E, Lo Cicero V, Brambilla A, Soncin S, Torre T, Milano G, et al. Exosomes from human car diac progenitor cells for therapeutic applications: development of a GMP-grade manufacturing method. Front. Physiol. 2018; 9: 1169.
- Pachler K, Lene T, Streif D, Dunai ZA, Desgeorges A, Feichtner M, et al. A Good Manufacturing Practice-grade standard protocol for exclusively human mesenchymal stromal cell-derived extracellular vesicles. Cytotherapy. 2017; 19: 458-472.
- Watson DC, Yung BC, Bergamaschi C, Chowdhury B, Bear J, Stellas D, et al. Scalable, cGMP-compatible purification of extracellular vesicles carrying bioactive human heterodimeric IL-15/lactadherin complexes. J. Extracell. Vesicles, 2018; 7: 1442088.
- Samoil V, Dagenais M, Ganapathy V, Aldridge J, Glebov A, et al. Vesicle-based secretion in schistosomes: analysis of protein and microRNA (miRNA) content of exosome-like vesicles derived from Schistosoma mansoni. Sci. Rep. 2018; 8: 3286.
- Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles, 2018; 7: 1535750.
- Smith ZJ, Lee C, Rojalin T, Carney RP, Hazari S, Knudson A, et al. Single exosome study reveals subpopulations distributed among cell lines with variability related to membrane content. J. Extracell. Vesicles, 2015; 4: 28533.
- Ramirez MI, Amorim MG, Gadelha C, Milic I, Welsh JA, Freitas VM, et al. Technical challenges of working with extracellular vesicles. Nanoscale, 2018; 10: 881-906.
- Osteikoetxea X, Balogh A, Szabó-Taylor K, Németh A, Szabó TG, Pálóczi K, et al. Improved characterization of EV preparations based on protein to lipid ratio and lipid properties. PLoS ONE, 2015; 10: e0121184.