Phagocytosis Escape-Reinforced Exosome Modification Service
- Molecular Expression Control: Surface anchoring of anti-phagocytosis proteins (e.g., CD47) via donor cell engineering or chemical conjugation.
- Shield Layer Construction: Use of supramolecular materials or biomimetic membrane fusion to reduce immunogenicity.
- In Vitro Phagocytosis Assay: Co-culture of exosomes with macrophages, quantitative analysis of phagocytosis using flow cytometry or high-content imaging.
- In Vivo Pharmacokinetics: Tracing labeled exosomes in animal models to determine plasma half-life and tissue accumulation efficiency.
Exosomes are natural nano-sized vesicles (30–150 nm in diameter) actively secreted by cells, carrying biologically active molecules such as proteins, nucleic acids (e.g., mRNA, miRNA), and lipids. Thanks to their low immunogenicity, excellent tissue penetration, and inherent targeting ability, exosomes have emerged as next-generation drug delivery vehicles. In fields such as tumor-targeted therapy, gene therapy, and immune modulation, exosomes can efficiently deliver therapeutic cargo to disease sites, thereby enhancing treatment efficacy and reducing systemic toxicity.
However, unmodified natural exosomes are prone to rapid clearance by the mononuclear phagocyte system (MPS), especially by macrophages in the liver and spleen, which recognize them as "foreign" particles. This leads to a shortened circulation half-life and reduced targeting efficiency. To address this challenge, Phagocytosis Escape-Reinforced Exosome Modification strategies have been developed to enhance the in vivo stability and delivery efficiency of exosomes. The primary goal is to reduce MPS-mediated clearance, extend blood circulation time, and improve targeted delivery outcomes.
Parada, N. et al. J Adv Res. 2021.
Figure 1. Interaction of Exosomes with Macrophages
Core Phagocytosis Escape-Reinforced Exosome Modification Strategies:
1. Integration of “Don’t Eat Me” Signals: Overexpression of immunosuppressive proteins such as CD47 or STC-1 on the exosomal surface blocks phagocytosis signaling by binding to macrophage receptors like SIRPα.
2. Construction of Immune Shielding Layers: Techniques such as PEGylation or biomimetic membrane camouflage (e.g., fusion with red blood cell membranes) conceal immunogenic epitopes on the exosome surface.
3. Co-Design of Targeting and Stealth Functions: Simultaneous incorporation of targeting ligands (e.g., tumor-specific antibodies) and anti-phagocytosis molecules to achieve synergistic optimization of function.
Service at MtoZ Biolabs
To overcome the immunoclearance bottleneck in exosome-based delivery, MtoZ Biolabs offers Phagocytosis Escape-Reinforced Exosome Modification Service, aimed at enabling long-circulating, target-enhanced exosomes through precise surface engineering. Leveraging our proprietary molecular modification platform and multidisciplinary expertise, we provide full-process solutions from design to functional validation, accelerating the clinical translation of exosome therapeutics. Our service includes:
1. CD47-Overexpressing Exosomes: Engineered via donor cell genetic modification to express high levels of CD47, activating the SIRPα signaling pathway and reducing macrophage uptake.
2. PEG-Modified Exosomes: Covalent conjugation of polyethylene glycol molecules at controllable density to shield macrophage recognition sites.
3. Biomimetic Membrane Fusion Technology: Fusion of exosomes with red blood cell membranes to endow natural immune escape properties.
4. Custom Dual-Function Designs: Integration of both immune-evading elements and active targeting ligands for optimal in vivo performance.
Analysis Workflow
1. Needs Assessment and Strategy Design
Based on the client’s goals (e.g., target tissue, drug payload), we recommend optimal modification strategies such as CD47 expression, PEGylation, or membrane fusion.
2. Exosome Engineering and Modification
3. Functional Evaluation
4. Comprehensive Report Delivery
Includes physicochemical characterization (size, surface markers), functional assay data, and custom optimization recommendations.
Service Advantages
Multidisciplinary Technical Team: Expertise spanning molecular biology, nanotechnology, and immunology to support tailored modification strategies.
End-to-End Project Support: From design and modification to validation and scale-up process development, minimizing client R&D risk.
Flexible Engineering Options: Multiple strategies such as CD47 overexpression, PEGylation, or biomimetic fusion, with support for combined approaches (e.g., “stealth + targeting” designs).
High Reproducibility and Compliance: Production standards ensure lot-to-lot consistency, suitable for preclinical research requirements.
Applications
1. Tumor-Targeted Therapy
Prolongs drug residence time in the tumor microenvironment and reduces off-target toxicity.
2. Gene and Cell Therapy
Protects gene delivery vectors (e.g., CRISPR components) from immune clearance, enhancing editing efficiency.
3. Autoimmune Disease Intervention
Enables targeted delivery of anti-inflammatory agents while minimizing systemic immune activation.
Case Study
1. Construction of Exosomes that Overexpress CD47 and Evaluation of Their Immune Escape
This study aimed to construct exosomes (EXOs^CD47) that overexpress CD47 and evaluate their immune escape abilities both in vitro and in vivo. Exosomes derived from adipose tissue-derived mesenchymal stromal cells (ADMSCs) were engineered to express high levels of CD47. Through nanoflow cytometry, ultra-high-definition laser confocal microscopy, and macrophage phagocytosis assays, EXOs^CD47 exhibited significantly enhanced retention in vivo (1.377-fold increase) and strong anti-phagocytic properties in vitro compared to control exosomes, demonstrating superior immune evasion and potential as drug carriers. MtoZ Biolabs offers specialized Phagocytosis Escape-Reinforced Exosome Modification Service based on CD47 engineering to reinforce resistance to phagocytosis. Utilizing precise bioengineering strategies, exosomes stably and efficiently express CD47, significantly enhancing immune evasion from macrophages, extending systemic circulation time, and optimizing their efficiency as drug delivery vehicles.
Ben, XY. et al. Front Bioeng Biotechnol. 2022.
Figure 2. Vector Plasmid with CD47 Overexpression
2. A Combined ‘‘Eat Me/Don’t Eat Me’’ Strategy Based on Exosome for Acute Liver Injury Treatment
This study proposed an exosome-based combined "eat me/don’t eat me" strategy for the treatment of drug-induced liver injury (DILI). Researchers employed RLTR peptide surface modification to target liver sinusoidal endothelial cells (LSECs), engineered exosomal expression of CD47 to evade macrophage phagocytosis, and encapsulated Wnt2 mRNA into exosomes via lentiviral packaging. Results indicated that the engineered RLTR-Wnt2@ExoCD47 achieved LSEC-specific accumulation and significant hepatoprotective effects in murine liver injury models. We offer Phagocytosis Escape-Reinforced Exosome Modification Service focused on reinforcing resistance to phagocytic clearance. Through engineering exosomal surface molecules, our service effectively reduces macrophage uptake, prolongs circulation time, and enhances tissue-specific targeting. Additionally, customized integration of targeting peptides and functional payloads supports diverse therapeutic and drug-delivery applications.
Du, W. et al. Cell Rep Med. 2025.
Figure 3. CD47 Engineering Exosome Escapes the Phagocytosis by Macrophages
Insufficient immune evasion remains one of the greatest barriers to the clinical translation of exosome therapeutics. At MtoZ Biolabs, we are committed to delivering high-performance, cost-effective, and reliable solutions for exosome immune escape engineering. Our goal is not only to provide a single technology but to collaboratively explore the future frontiers of exosome-based delivery, helping you overcome immunological barriers and unleash the full therapeutic potential of your innovations. Contact MtoZ Biolabs to empower your exosome therapeutics with immune stealth and targeted precision—let us help you accelerate the next generation of precision medicine.
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