Validating the Targeting Specificity of Sialic Acid Binding Polymeric Nanomaterials

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dc.contributor.authorCuprija, Ajsa
dc.contributor.departmentChalmers tekniska högskola / Institutionen för biologi och biotekniksv
dc.contributor.examinerStubelius, Alexandra
dc.contributor.supervisorStubelius, Alexandra
dc.date.accessioned2022-07-01T06:53:13Z
dc.date.available2022-07-01T06:53:13Z
dc.date.issued2022sv
dc.date.submitted2020
dc.description.abstractInhibiting inflammation at an early stage is a key for treatment of e.g. cancer and rheumatoid arthritis. Early in the recruitment of leukocytes, glycans (carbohydrate chains of glycoproteins on the cell-membrane) are highly involved in the cell-to-cell signaling. Sialic acid (Sia) is positioned at the terminal end of glycans and also plays a crucial role in leukocyte recruitment. Boronic acids have been shown to bind diols (pairs of hydroxyl groups) found on carbohydrates, and they have exhibited a particular affinity towards Sia compared to e.g. mannose or glucose. Thus, it is hypothesized that pro-inflammatory signals can be inhibited using synthetic nanoparticles (NPs) that, via boronic acid, bind to Sia and consequently to glycans. In this project, poly(lactic-co-glycolic acid) NPs coated with poly(ethylene glycol) (PLGA-PEG) were synthesized by nanoprecipitation. In order to increase the targeting specificity towards Sia, phenylboronic acid (PBA) was conjugated to the amine-rich branched polyethyleneimine (PEI), which in turn was conjugated to poly(ethylene glycol) methyl ether (mPEG) for successful attachment to the PLGA core. Dynamic light scattering (DLS) data showed that a 1:10 ratio of mPEG-PEIPBA to PEG surfactant provided more stability in the hydrodynamic NP size (223 ±8 nm in milli-Q water) and a more positive zeta-potential (~30 mV). A 1:30 ratio resulted in a larger NP size (278 ±11 nm, in milli-Q water) and a lower zeta-potential (~18 mV). Non-hydrodynamic size and shape of the NPs was confirmed with scanning electron microscopy (SEM) images. In a resazurin viability assay, the 1:30 NPs showed no cytotoxicity at concentrations up to 450 μg/mL after 24 hours of incubation with U937 monocytes. Isothermal titration calorimetry (ITC) data confirmed that a higher number of PBA molecules per PEI polymer provides a promising targeting specificity towards the sialic acid Neu5Ac in pH6, which is more alike the conditions of inflamed tissues. These preliminary results illustrate the potential of PBA-coated polymeric NPs to target Sia in inflammatory conditions. However, further work is required to confirm their binding specificity to whole glycans and to observe an inhibiting effect on leukocyte recruitment.sv
dc.identifier.urihttps://hdl.handle.net/20.500.12380/304991
dc.language.isoengsv
dc.setspec.uppsokLifeEarthScience
dc.titleValidating the Targeting Specificity of Sialic Acid Binding Polymeric Nanomaterialssv
dc.type.degreeExamensarbete för masterexamensv
dc.type.uppsokH
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