Macrophage reprogramming plays an essential role in maintaining the steady state of the immune system and is involved in the processes of many diseases. Nanoparticles can perturb the polarization and reprogramming of macrophages, affect their immunological function and, therefore, affect the pathological process of disease. Creative Biolabs has organized a staff of outstanding scientists who have engaged in reprogramming macrophages for many years. Based on our cutting-edging Macrophage Therapeutics Development Platform, optimally designed nanoparticles for the modulation of macrophage reprogramming will provide new solutions for treating diseases.

Employing Nanoparticles for Macrophage Reprogramming

As one of the most effective cell types in the emergency response system of the human body, macrophages modulate host defense, inflammatory processes, and homeostasis. With powerful abilities of cell engulfment, antigen presentation and cytokine secretion, macrophages govern the initiation and resolution stages of innate and adaptive immunity. Macrophages are vital regulators of the host defense in organisms. In response to different local microenvironments, resting macrophages (M0) can be polarized into different phenotypes, pro-inflammatory (M1) or anti-inflammatory (M2), and perform different roles in different physiological or pathological conditions.

With unique physicochemical characteristics, nanoparticles are widely used in the biomedical field for disease diagnosis and therapy. Nanoparticles are foreign substances, and macrophages play crucial roles in the recognition, processing, and clearance of nanoparticles in vivo. M0, M1 and M2 have distinct uptake capacities for nanoparticles. Meanwhile, nanoparticles can differentially modulate macrophage polarization and reprogramming. Interactions of nanoparticles with macrophages are attracting more and more attention in medical applications and toxicological studies.

Fig.1 Fluorescence microscopy analysis of the uptake of miR-223-encapsulated in hyaluronic acid-poly(ethyleneimine) nanoparticles.^1,2

Reprogramming Macrophages by Nanoparticles at Creative Biolabs

Previous studies have shown that nanoparticles can induce M0 macrophage toward M1 phenotype or M2 phenotype, such as the usage of cell membrane-derived nanoghosts for reprogramming macrophages. Nanoparticles can induce inflammation in the animal models via M1 polarization and the expression of M2 subtype markers can be markedly increased on the surface of bioactive nanoparticles. Creative Biolabs has a highly experienced team of scientists and quality staff that have a long history in the study of nanoparticles for macrophage reprogramming. The physicochemical properties of nanoparticles, including chemical composition, size, and surface coatings, can differentially regulate macrophage polarization.

Creative Biolabs is well equipped and versed in shifting macrophages from pro-inflammatory M1 toward anti-inflammatory M2 phenotype or from M2 to M1 by employing surface-functionalized nanoparticles. We continue to serve our global clients with professionalism and expertise in macrophage reprogramming. For more detailed information on macrophage reprogramming, please feel free to contact us or directly send us an inquiry.

Related Products

Creative Biolabs designs and develops a range of useful products to aid our customers' research in macrophage reprogramming.

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Service Features

Customizable Nanoparticle Designs

Our team optimizes nanoparticle properties including material composition, surface functionalization, size and charge control.

Precise Payload Delivery

Payload options include siRNA or miRNA, small molecules, proteins and peptides, and CRISPR/Cas9 systems.

Advanced Assays

We provide a set of powerful assays, including polarization assays, functional studies, and high-throughput screening.

Safety and Biocompatibility Evaluation

Evaluations include compatibility and cytotoxicity tests, evaluation of immune response to nanoparticles, and analysis of nanoparticle degradation and clearance pathways.

Comprehensive Data Analysis and Reporting

Detailed scientific reports and comprehensive data analysis including quantitative and qualitative results of macrophage reprogramming, statistical analysis, etc.

Regulatory Compliance

We adhere to strict ethical and regulatory standards for preclinical research. This ensures that your research is conducted in a responsible and reproducible manner.

Publications

Iron oxide nanoparticles (IONPs) have been synthesized and functionalized for a wide range of uses, which in recent years has enhanced research interest in their interaction with macrophages. In a review, Vladimir Mulens-Arias et al. reviewed and discussed what is currently known about IONP-induced mechanisms of immune regulation, with a primary focus on macrophage polarization and reprogramming.

IONPs can interact with cell surface receptors such as TLRs to activate the MAPK signaling pathway. Once internalized by macrophages, IONPs are encapsulated in lysosomes where they are biodegraded. As a result, iron atoms are released into the cytoplasm where it participates in the Fenton reaction and generates ROS. As a result, triggering transcriptional reprogramming, for example involving NF-κB and NRF2 target genes.

Fig. 2 Overview of the effects of IONPs on macrophage polarization.³

Scientific Resources

Learn More Macrophages in Diseases

Download Macrophage Polarization

Learn More How to Utilize Mitochondria to Study Macrophage Reprogramming

Learn More Macrophage-related Experimental Protocols

Q & A

Q: How do you ensure the reprogrammed macrophages maintain their new phenotype long-term?
A: We employ a comprehensive stability verification process that includes both in vitro and in vivo monitoring. Our nanoparticle formulations are designed with sustained-release properties that maintain the reprogramming factors at optimal levels. We perform regular phenotype assessments using flow cytometry, gene expression analysis, and functional assays at multiple time points to confirm stability.

Q: Can you reprogram tissue-resident macrophages, and what's your success rate?
A: Yes, we can reprogram tissue-resident macrophages, though success rates vary by tissue origin. We've optimized tissue-specific protocols that account for the unique microenvironmental factors and use specialized nanoparticle formulations designed to overcome tissue-specific barriers. We provide a detailed characterization of the reprogramming efficiency for each tissue type.

Q: How do you verify that the macrophages have been successfully reprogrammed to the desired phenotype?
A: We employ a multi-parameter verification approach that includes flow cytometry analysis of surface markers, qPCR analysis of phenotype-specific genes, and functional assays such as phagocytosis capacity and cytokine production profiles. We also perform RNA-seq analysis to confirm broad transcriptional changes and secretome analysis to verify the functional state. All results are compared against established positive controls and baseline measurements.

Q: Can you customize the reprogramming protocol?
A: Yes, we offer customized reprogramming protocols based on your specific research needs. We can modify nanoparticle composition, cargo selection, and reprogramming conditions to achieve desired phenotypes relevant to your disease model. This includes optimization for specific inflammatory profiles, phagocytic capacity, or metabolic states. We'll work with you to design a validation strategy that includes disease-relevant functional assays and markers.

References

1. Tran, Thanh-Huyen, Swathi Krishnan, and Mansoor M. Amiji. "MicroRNA-223 induced repolarization of peritoneal macrophages using CD44 targeting hyaluronic acid nanoparticles for anti-inflammatory effects." PloS one 11.5 (2016): e0152024.
2. Under Open Access license CC BY 4.0, without modification.
3. Mulens-Arias, Vladimir, José Manuel Rojas, and Domingo F. Barber. "The use of iron oxide nanoparticles to reprogram macrophage responses and the immunological tumor microenvironment." Frontiers in immunology 12 (2021): 693709. Distributed under Open Access license CC BY 4.0, without modification.