PNExo™ Exosome-Aloe(PNE-FLA16)

Benefits of Aloe: Bioactive Components and Biological Activities

Aloe vera is rich in diverse bioactive compounds that contribute to its antioxidant, anti-inflammatory, and skin-supporting properties. Research highlights several key components and their mechanisms:

• Anthraquinones (e.g., Aloe-emodin, Aloin): Exhibit antioxidant and anti-inflammatory effects by modulating NF-κB/MAPK pathways, and show antimicrobial activity by disrupting microbial protein and DNA synthesis.
• Polysaccharides (e.g., Acemannan): Support immune activation, promote fibroblast growth and collagen production for wound repair, and help protect against oxidative and metabolic stress.
• Sterols (e.g., β-Sitosterol): Inhibit COX-2 to reduce inflammation and stabilize membranes under oxidative conditions.
• Enzymes (e.g., SOD, Bradykininase): Neutralize free radicals and reduce edema, aiding in cellular protection.
• Vitamins/Minerals (e.g., C, E, Zinc): Contribute to antioxidant defense and tissue regeneration.
• Flavonoids: Provide additional anti-inflammatory support and oxidative stability.

What Are Aloe-Derived Exosomes?

Aloe-derived exosomes are nanoscale extracellular vesicles (EVs) obtained from Aloe plant tissues. They act as natural carriers of Aloe-specific bioactive molecules and play roles in plant-based intercellular communication. Their main characteristics include:

• Structural Features: Spherical in shape with a lipid bilayer membrane, typically 100-200 nm in diameter. Particle size analysis shows a main distribution peak around 200 nm, with a minor range extending to 300-600 nm.
• Molecular Composition: Contain Aloe-specific bioactive components such as polysaccharides, functional proteins, and nucleic acids. SDS-PAGE analysis reveals major protein bands near 15 kDa, suggesting consistent protein enrichment.
• Isolation Method: The standard procedure involves homogenizing Aloe tissue, followed by a series of centrifugation steps. Low-speed centrifugation removes debris, and ultracentrifugation at 150,000 g allows for the collection of vesicles. The final pellet is resuspended in phosphate-buffered saline (PBS) for further use.

These features make Aloe-derived exosomes a unique category of plant EVs with growing relevance in natural product and nanobiotechnology research.

Isolation and Characterization of Aloe-Derived Extracellular Vesicle-Like Nanoparticles (EVAloe). (A) Schematic of EVAloe preparation involving differential centrifugation and sucrose gradient ultracentrifugation. (B) Transmission electron microscopy (TEM) image showing the morphology of EVAloe obtained from the 45% sucrose fraction. Scale bar: 100 nm. (C) Size distribution profile of EVAloe measured using nanoparticle tracking analysis (NTA). (D) SDS-PAGE analysis of EVAloe protein content using 10% polyacrylamide gel. (Zhou H, et al., 2023)

Advantages of Aloe-Derived Exosomes

Aloe-derived exosomes offer several distinct advantages compared to synthetic or animal-derived extracellular vesicles, making them an attractive platform for advanced biomedical and biotechnology research:

Excellent Biocompatibility and Safety

In vitro studies have shown that Aloe exosomes do not induce cytotoxic effects in fibroblasts or endothelial cells, supporting their suitability for prolonged exposure. Being plant-derived, they carry no risk of animal pathogen transmission and do not require genetic modification.

Anti-Inflammatory and Immunomodulatory Potential

Aloe exosomes have been shown to reprogram macrophages from pro-inflammatory (M1) to anti-inflammatory (M2) phenotypes, significantly reducing the expression of cytokines such as TNF-α and IL-6. In preclinical infection models, they alleviated tissue damage and cytokine storm responses. They have also demonstrated potential in promoting chronic wound repair by downregulating inflammatory genes (e.g., COX-2, iNOS) and enhancing fibroblast migration and proliferation.

Efficient Drug Delivery Capability

Due to their nano-scale size (100-200 nm), Aloe exosomes can penetrate biological barriers such as the skin or intestinal mucosa. Their lipid bilayer structure protects encapsulated agents from enzymatic degradation, improving stability and circulation time. They have been used to deliver hydrophobic drugs, such as indocyanine green, for targeted photo-therapeutic studies, and inherently carry bioactive Aloe compounds like acemannan without chemical modification.

Rich in Bioactive Components

Aloe exosomes contain a variety of naturally functional molecules.

• Acemannan (Polysaccharide): Stimulates immune activity, supports antiviral responses, and promotes wound healing.
• Aloe-emodin (Phenolic compound): Exhibits antioxidant and anti-tumor properties.
• β-Sitosterol (Sterol): Contributes to anti-inflammatory and cholesterol-lowering effects.
• Superoxide Dismutase (Enzyme): Acts as a free radical scavenger and protects against oxidative damage.

Scalability and Manufacturing Feasibility

Cultivation of Aloe vera through optimized tissue culture protocols enables high propagation efficiency, with survival rates above 90%. Innovative extraction methods, including supercritical CO₂ and enzyme-assisted membrane filtration, enhance yield and preserve the integrity of heat-sensitive or bioactive components.

These combined advantages position Aloe-derived exosomes as a promising, plant-based extracellular vesicle platform for diverse research applications.

References

1. Kim M K, Choi Y C, Cho S H, et al. The antioxidant effect of small extracellular vesicles derived from aloe vera peels for wound healing. Tissue Engineering and Regenerative Medicine. 2021, 18: 561-571.
2. Zeng L, Wang H, Shi W, et al. Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy. Journal of Nanobiotechnology. 2021, 19: 1-24.
3. Kim M, Park J H. Isolation of aloe saponaria-derived extracellular vesicles and investigation of their potential for chronic wound healing. Pharmaceutics. 2022, 14(9): 1905.
4. Kim D M, Kim W J, Lee H K, et al. Skin improvement of the composition containing nano-exosome derived from Aloe vera bark callus as new type of transdermal delivery system. Asian Journal of Beauty and Cosmetology. 2023, 21(1): 117-130.
5. Zhou H, Peng K, Wang J, et al. Aloe-derived vesicles enable macrophage reprogramming to regulate the inflammatory immune environment. Frontiers in Bioengineering and Biotechnology. 2023, 11: 1339941.
6. Calzoni E, Bertoldi A, Cesaretti A, et al. Aloe Extracellular Vesicles as Carriers of Photoinducible Metabolites Exhibiting Cellular Phototoxicity. Cells. 2024, 13(22): 1845.
7. Zeng L, Shi W, Chen K, et al. Indocyanine Green Aggregation-Induced Hypotonic Stress to Remodel Aloe Exosome-like Vesicles for Enhanced Tumor Penetration and Phototherapy. ACS nano. 2025, 19(16): 15425-15443.
8. Sun Z, Zheng Y, Wang T, et al. Aloe Vera Gel and Rind-Derived Nanoparticles Mitigate Skin Photoaging via Activation of Nrf2/ARE Pathway. International Journal of Nanomedicine. 2025: 4051-4067.

Case Study 1: Aloe-Derived Nanovesicles as Natural Drug Carriers (Zeng L, 2021)

A study investigated aloe-derived nanovesicles (ADNVs) as a natural and stable nanocarrier system for drug delivery. Researchers successfully isolated ADNVs from aloe gel (gADNVs) and rind (rADNVs), with optimized conditions yielding monodispersed vesicles under 150 nm, suitable for systemic delivery. Compared to synthetic liposomes, gADNVs demonstrated superior structural stability, antioxidant capacity, and resistance to detergent-induced membrane disruption.

In drug-loading experiments, indocyanine green (ICG) was efficiently encapsulated in gADNVs, retaining over 90% of the active compound after 30 days of storage, compared to only 74% retention in ICG-loaded liposomes. Furthermore, ICG/gADNVs maintained phototherapeutic activity in vitro and inhibited melanoma tumor growth in vivo more effectively than control formulations. Fluorescence imaging revealed that gADNVs had enhanced transdermal penetration, reaching deeper skin layers than both free dye and liposome formulations.

The study highlights aloe-derived nanovesicles as promising plant-based carriers with high biocompatibility, long-term stability, and effective delivery performance, particularly suited for photosensitive or hydrophobic compounds.

Figure 1. Evaluation of ICG Stability and Leakage in gADNVs Compared to Liposomes and Free ICG. (A) UV-vis spectra of ICG/gADNVs, ICG/Lips, and free ICG after 12 h at 55 °C. (B) Thermal stability comparison of ICG in different carriers. A/A₀ indicates the ratio of absorbance before and after heating. (C) Stability of ICG/gADNVs, ICG/Lips, and free ICG in serum. (D) Long-term retention rates of ICG in gADNVs and liposomes over 60 days.

Figure 2. Enhanced Dermal Penetration of DiO via gADNVs Compared to Free DiO and Liposomes. Laser scanning confocal microscopy images showing the skin penetration of free DiO, DiO-loaded gADNVs, and DiO-loaded liposomes (DiO/Lips). DiO/gADNVs penetrated into the dermis with a broader distribution, while free DiO and DiO/Lips primarily remained in the epidermis, suggesting the potential of gADNVs as effective percutaneous drug carriers.

Case Study 2: Aloe saponaria-Derived EVs for Chronic Wound Research (Kim M, 2022)

A study evaluated the potential of Aloe saponaria-derived extracellular vesicles (AS-EVs) for chronic wound healing. AS-EVs were isolated using a PEG-based precipitation method and confirmed to be spherical nanoparticles under 200 nm. Importantly, they showed no cytotoxicity in dermal fibroblasts, endothelial cells, or macrophages at concentrations up to 5 × 10⁹ particles/mL.

Functionally, AS-EVs reduced LPS-induced expression of inflammatory markers IL-6 and IL-1β by over 70%, indicating strong anti-inflammatory potential. They also promoted fibroblast proliferation (2.3-fold increase) and migration (over 3-fold), both essential for tissue repair. In tube formation assays, endothelial cells treated with AS-EVs formed longer capillary-like structures, up to 33% longer than controls, suggesting enhanced angiogenic activity.

These results support the role of Aloe-derived EVs as safe, plant-based vesicles with promising applications in inflammation modulation and tissue regeneration research.

Figure 1. AS-EVs Promote Proliferation and Migration of Human Dermal Fibroblasts (HDFs). (A) WST-8 assay evaluating the viability of HDFs after 48 h incubation with AS-EVs in serum-free DMEM/F12. (B) Transwell migration assay showing enhanced migration of HDFs following 24 h AS-EVs treatment. Cells on the bottom side of the membrane were stained with crystal violet (CV) and fixed with 4% paraformaldehyde. Scale bar: 200 μm. (C) Quantification of migrated cells by measuring CV absorbance at 560 nm.

Figure 2. AS-EVs Enhance Capillary-Like Tube Formation in Human Umbilical Vein Endothelial Cells (HUVECs). (A) Representative images of capillary-like structures formed by HUVECs after 16 h of AS-EVs treatment on Matrigel in EGM-2 medium. Scale bar: 200 μm. (B) Quantification of total tube length using ImageJ.

References

1. Zeng L, Wang H, Shi W, et al. Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy. Journal of Nanobiotechnology. 2021, 19: 1-24.
2. Kim M, Park J H. Isolation of aloe saponaria-derived extracellular vesicles and investigation of their potential for chronic wound healing. Pharmaceutics. 2022, 14(9): 1905.

• What makes Aloe-derived exosomes different from synthetic liposomes or animal-sourced exosomes?

  Aloe-derived exosomes are plant-based nano-vesicles with natural lipid bilayers and plant-specific bioactive cargo like glucose ceramides, phenolic compounds (aloesin, aloe-emodin), and β‑sitosterol. Unlike liposomes or animal-derived vesicles, they offer high biocompatibility, reduced immunogenic risk, and inherent antioxidant and anti-inflammatory properties, all without genetic modification.

• Are Aloe exosomes safe for cell culture and preclinical use?

  Yes. Aloe-derived exosomes have shown no cytotoxic effects in fibroblasts, endothelial cells, or red blood cells. They do not elevate pro-inflammatory cytokines or cause organ damage in tested models. Their plant origin also avoids the risk of animal-borne pathogens.

• What is the purity and quality of PNExo™ Exosome‑Aloe?

  PNExo™ is produced using a refined isolation process that includes centrifugation, filtration, and ultra-purification. This method ensures high-purity plant exosomes with minimal contaminants and consistently yields intact vesicles suitable for downstream research or manufacturing.

• How does Aloe-derived exosome stability compare to liposomes?

  Studies show that Aloe-derived vesicles resist detergent and peroxide-induced damage better than synthetic liposomes. They also preserve antioxidant lipids and proteins under stress conditions, providing enhanced stability for functional bioactive delivery.

• How are PNExo™ exosomes characterized for quality control?

  Each batch of PNExo™ undergoes size distribution analysis using techniques such as nanoparticle tracking analysis (NTA) or dynamic light scattering (DLS). Protein profiles are verified by SDS-PAGE to ensure consistency, and vesicle morphology is confirmed by electron microscopy.

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