Track: Formulation and Delivery - Biomolecular - Drug Delivery - Other
Category: Late Breaking Poster Abstract
Lipid Nanoparticles for M2-Type Tumor Associated Macrophages Specific Drug Delivery
Purpose: Tumor associated macrophages (TAMs) which are found to be abundant in tumor microenvironment play a pivotal role in tumor growth, cancer immunosuppression and drug resistance. It is considered that the acidic and hypoxic tumor microenvironments can ”educate” the TAMs into a tumor promotion phenotype (M2-type TAMs). Accordingly, targeting TAMs has been a promising therapeutic strategy in cancer immunotherapy. Lipid nanoparticles have been widely studied for cancer immunotherapy. However, the shape effect of lipid nanoparticles on TAM specific drug delivery is still unknown. The purpose of this study was to understand the shape effect on the internalization ability of lipid nanoparticles in M2-type TAMs. Methods: Two types of lipid nanoparticles with different shapes (i.e. spherical and disk) were prepared. The spherical lipid nanoparticle (liposome, s-Lip) was prepared using Nanoassemblr™ instrument and the disk-shaped lipid nanoparticle (nanodisc) was prepared using a thin film-hydration method. RAW264.7 cell lines were polarized to M2-type using IL-4 and used as the cell model. The s-Lip and nanodisc were labeled with a fluorescence dye Cy3, and the internalization behavior of the two types of lipid nanoparticles in M2-type RAW264.7 cells was investigated. The cellular uptake of s-Lip and nanodisc in RAW264.7 cells was observed using a confocal laser scan microscope and quantified via flow cytometry. The cytotoxicity of the two lipid nanoparticles was also investigated in M2-type RAW264.7 cells. Results: The s-Lip with a spherical shape had a particle size of 45.3±1.9 nm and the nanodisc with a disk shape had a particle size of 17.7±0.4 nm. Both s-Lip and nanodisc can be internalized by M2-type macrophages at 4 hr as shown in Figure 1A. The flow cytometry results (Figure 1B) indicated that the uptaken efficiency of the nanodisc (28.12±6.2%) was more than that of the s-Lip (11.01±0.5%) (p< 0.05). The cell viability of liposome and nanodisc (Figure 1C) were over 80% at all concentrations studied, indicating that there was no toxicity on the M2-type RAW264.7 cells. Conclusion: Lipid nanoparticles with different shapes were prepared for M2-type TAM specific drug delivery. Nanodisc was more efficient for M2-type TAMs-specific drug delivery with non cytotoxicity observed compared to small-sized liposomes. This research could help elucidate the influence of shape on design of TAMs-specific drug delivery systems.
DeNardo, David G., and Brian Ruffell. Macrophages as regulators of tumour immunity and immunotherapy. Nature Reviews Immunology19.6 (2019): 369-382.
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