Targeted delivery of functionalized PLGA nanoparticles to macrophages by complexation with the yeast Saccharomyces cerevisiae

Abstract

Nanoparticles (NPs) are able to deliver a variety of substances into eukaryotic cells.However, their usage is often hampered by a lack of specificity, leading to the undesired uptake of NPs by virtually all cell types. In contrast to this, yeast is known to be specifically taken up into immune cells after entering the body. Therefore, we investigated the interaction of biodegradable surface-modified poly(lactic-co-glycolic acid) (PLGA) particles with yeast cells to overcome the unspecificity of the particulate carriers. Cells of different Saccharomyces cerevisiae strains were characterized regarding their interaction with PLGA-NPs under isotonic and hypotonic conditions. The particles were shown to efficiently interact with yeast cells leading to stable NP/ yeast-complexes allowing to associate or even internalize compounds. Notably, applying those complexes to a coculture model of HeLa cells and macrophages, the macrophages were specifically targeted. This novel nano-in-micro carrier system suggests itself as a promising tool for the delivery of biologically active agents into phagocytic cells combining specificity and efficiency.

The pro‐inflammatory response of macrophages regulated by acid degradation products of poly(lactide‐co‐glycolide) nanoparticles

“…On the other hand, IL‐4 and IL‐13 released from Th2 induce M2 polarization, which in turn promoting Th2 differentiation by producing chemokine (C‐C motif) ligand (CCL) 17 and CCL 22. M2 subtype macrophages are responsible for immunosuppression, which can produce anti‐inflammatory cytokines IL‐10, express the related surface marker CD206, and encourage tissue regeneration in the later period [27, 28]. Hence, to further promote the application of biodegradable synthetic polymers, it is important to sufficiently discuss the exact regulatory mechanism for such polymers and their degradation products on cellular processes of macrophages.…”

Macrophages as Promising Carriers for Nanoparticle Delivery in Anticancer Therapy

“… 11 The acquisition of appropriate functions is possible due to the phenotypic plasticity of the macrophages in response to stimuli from the environment. 12 , 13 …”

3D imaging and quantification of PLL coated fluorescent ZnO NP distribution and ROS accumulation using laser scanning confocal microscopy

“…Determination of bioavailability and toxicity of such nanoparticles (NPs) require the use of imaging approaches, ideally with three dimensional (3D) capabilities. Monitoring cell‐NP interaction for cancer cells using high‐resolution imaging may provide insights into the attachment of particles on the cell surface 4–10 . To quantify the concentration of internalized particles it is crucial to perform imaging of various z‐sections and perform 3D reconstruction of fluorescent intensity using confocal microscopy 11,12 .…”

“…Monitoring cell-NP interaction for cancer cells using high-resolution imaging may provide insights into the attachment of particles on the cell surface. [4][5][6][7][8][9][10] To quantify the concentration of internalized particles it is crucial to perform imaging of various z-sections and perform 3D reconstruction of fluorescent intensity using confocal microscopy. 11,12 Recent advancement in 3D visualization of NP distribution in living cells and tissue involves volumetric imaging using laser scanning confocal microscope (LSCM).…”