Quantitative evaluation of cellular internalization of polymeric nanoparticles within laryngeal cancer cells and immune cells for enhanced drug delivery

Abstract

Clinical translation of poly (lactic-co-glycolic acid) (PLGA)-based nanomedicine is limited, partly because of the poor delivery efficiency resulting from non-specific phagocytosis by phagocytes. Understanding the nanoparticle interplay between cancer cells and immune cells remains largely elusive. In this study, a quantitative investigation on cellular internalization of fluorescent PLGA particles (100 nm, 500 nm, and 1 µm) against laryngeal carcinoma cells with or without monocytes/macrophages in monoculture or co-culture systems was first performed. PLGA particles at concentrations of 5–20 µg/mL show superior biocompatibility except for 500 nm and 1 µm PLGA particles at 20 µg/mL slightly reduce cell viability. Microscopic observation has discovered all three sizes of particles are effectively ingested by both cancer cells and macrophages; however, quantitative fluorescence examination has disclosed that the uptake index of cancer cells (mean intracellular particle fluorescence per cancer cell normalized to that of per macrophage) is substantially declined for all PLGA particles in co-cultures compared to that in monocultures (1.35–1.05, 1.50–0.59, and 1.4–0.47 for 100 nm, 500 nm, and 1 µm particles, respectively). Quantitative analysis using flow cytometry further confirmed the reduced uptake index of cancer cells in co-cultures, but higher particle counts per macrophage. It has also been found that the formation of multinucleated giant cells via the fusion of macrophages increased after PLGA treatment, which could be further exploited as a potential approach for tumor drug delivery. Overall, these findings provide new insights into the interaction of nanoparticle-immune-cancer cells, which may facilitate the application of PLGA-based nanocarriers for the treatment of laryngeal carcinoma.

Delivery of costimulatory blockade to lymph nodes promotes transplant acceptance in mice

“…PLGA is widely used for synthesis of NPs, as it can be engineered and characterized readily and exhibits a good safety profile (119)(120)(121)(122)(123)(124)(125)(126)(127). PLGA NPs with diameters of approximately 100 nm have demonstrated superior biocompatibility and lower uptake by macrophages, as compared with larger NPs (128). Our live imaging shows that the early interaction occurs at the apical site of HEVs and their subsequent internalization into HEV cells from where these NPs are exocytosed into LN stroma near the peri-HEV environment using microtubules.…”

Suppression of Autoimmune Rheumatoid Arthritis with Hybrid Nanoparticles That Induce B and T Cell Tolerance to Self-Antigen

“…The increased distribution of CD22L-NP-OVA in spleen is consistent with targeting to CD22 expressing B cells and cDCs, which represent 44–58% and 1.5% of the cellular content of spleen, respectively. We also believe that at this time point (24 h), phagocytic cells like macrophages or monocytes can also contribute to the uptake of both targeted and nontargeted NPs. , …”

“…We also believe that at this time point (24 h), phagocytic cells like macrophages or monocytes can also contribute to the uptake of both targeted and nontargeted NPs. 35,36 To assess NP clearance from peripheral blood, the fluorescent particles were injected intravenously (iv), and mice were bled via the retro-orbital sinus at 1.5, 3, 6 and 24 h post-injection. The blood was placed in wells of a black ELISA plate and subjected to fluorescence imaging to quantitate the particles present in the blood, as shown in Figure 4C,D.…”

Nanosized Drug Delivery Systems to Fight Tuberculosis

“…The introduction of inhalable formulations would represent unprecedented progress for the treatment of TB. Therefore, it is not surprising that all first-line antitubercular drugs have been studied for pulmonary administration: INH [ 94 , 95 , 96 ], RFP [ 97 , 98 , 99 ], PZA [ 100 , 101 ], and EMB [ 102 ]. Several routes can be used for drug pulmonary administration [ 103 ].…”

“…As mentioned above, it is also possible to modify the surface of NPs with various ligands, including mannose residues, to favor their internalization by macrophages in infected tissues [ 96 , 104 , 112 , 113 , 114 ]. As an additional example, Marcianes et al (2020) developed biodegradable PLGA microparticles for the pulmonary administration of gatifloxacin, using labrafil as a surface modifier to actively target alveolar macrophages [ 115 ].…”