Macrophages hold great potential in drug delivery because they can sense chemotactic cues and home to tumors with high efficiency. Integrating state-of-the-art Macrophage Therapeutics Development Platform as well as industry-leading expertise in macrophage engineering, Creative Biolabs has the necessary expertise and capabilities to provide overall solutions, focusing on innovative research.

Macrophages as Direct Drug Carriers

Previous studies have indicated that drug-loaded macrophages can be constructed by incubating drugs with liver macrophages. For instance, DOX-loaded RAW 264.7 macrophages were used to treat metastatic 4T1 tumors. DOX did not significantly affect macrophage targeting and viability. Treatment with DOX-loaded macrophages can effectively prolong the lifespan of 4T1-tumor mice. Moreover, anti-cancer drugs are used to deplete TAMs from the tumor microenvironment. However, it should be realized that the anticancer drugs also had toxic effects on M1 macrophage carriers. Anticancer agents (such as cisplatin and gemcitabine) did not significantly affect macrophage cell viability at a certain dose range, but cell proliferation was inhibited. Therefore, when using macrophages as direct drug carriers, the cytotoxic effects of these drugs on macrophage activity needs to be carefully considered.

Macrophages as Indirect Drug Carriers

Loaded nanoparticles (NPs) that contain drugs instead of directly loading drugs is common macrophage-based drug delivery systems. The reason is that loaded NPs can reduce the toxicity of drugs to macrophages and, therefore, enhance the drug loading ratio. In the treatment, macrophages deliver NP-based therapeutics into the tumor site. Once recruited into the tumor, the macrophages can maintain the cargo NPs and then migrate/chemotaxis to the hypoxic regions of the tumor. Once in place, the NP-based therapeutic function could be initiated, resulting in total tumor destruction.

Fig.1 Schematic of Macrophage mediated biomimetic drug delivery into the hypoxic region of tumor.^1,2

Engineering Macrophages as Drug Carriers at Creative Biolabs

By leveraging the wealth of information on macrophage engineering, Creative Biolabs is pleased to help our clients with their project development in engineering macrophages as drug carriers. Given the complicated interactions between macrophages and their cargo, and the different effects of NPs of different sizes on macrophages, NPs with about 100 nm diameter are the best choice for loading drugs, due to an increased vector migration rate and effective absorption. The process of drug-loaded NPs into macrophages consists of 1) incubation of macrophages with drug-loaded NPs under appropriate culture conditions, 2) adhesion by different backpack layers, 3) low permeability resealing, and 4) electroporation.

Creative Biolabs offers accurate and effective solutions for researchers who are committed to developing macrophages as drug carriers. Our multidisciplinary teams work together closely to address these scientific and technical challenges. For more detailed information, please feel free to contact us or send us your inquiry or question.

References

1. Sun X., et al. "Macrophages mediated biomimetic drug delivery systems." J Nanomed. 2018; 1(1): 1003.
2. Under Open Access license CC BY 4.0, without modification.