2 research outputs found
Surface Modification of Polysaccharide-Based Nanoparticles with PEG and Dextran and the Effects on Immune Cell Binding and Stimulatory Characteristics
Surface
modifications of nanoparticles can alter their physical
and biological properties significantly. They effect particle aggregation,
circulation times, and cellular uptake. This is particularly critical
for the interaction with primary immune cells due to their important
role in particle processing. We can show that the introduction of
a hydrophilic PEG layer on the surface of the polysaccharide-based
nanoparticles prevents unwanted aggregation under physiological conditions
and decreases unspecific cell uptake in different primary immune cell
types. The opposite effect can be observed with a parallel-performed
introduction of a layer of low molecular weight dextran (3.5 and 5
kDa) on the particle surface (DEXylation) that encourages the nanoparticle
uptake by antigen-presenting cells like macrophages and dendritic
cells. Binding of DEXylated particles to these immune cells results
in an upregulation of surface maturation markers and elevated production
of proinflammatory cytokines, reflecting cell activation. Hence, DEXylated
particles can potentially be used for passive targeting of antigen
presenting cells with inherent adjuvant function for future immunotherapeutic
applications
Dual-Responsive Enzyme–Polysaccharide Conjugate as a Nanocarrier System for Enzyme Prodrug Therapy
Biopolymer-based drug delivery systems have gained considerable
attention in the field of nanomedicine. In this study, a protein–polysaccharide
conjugate was synthesized by covalent conjugation of the enzyme horseradish
peroxidase (HRP) with acetalated dextran (AcDex) via a thiol exchange
reaction. The resulting bioconjugate shows a dual-responsive behavior
in acidic and reductive environments to achieve a controlled release
of drugs. The self-assembly of this amphiphilic HRP–AcDex conjugate
allows the encapsulation of prodrug indole-3-acetic acid (IAA) into
the hydrophobic polysaccharide core. Under slightly acidic conditions,
the acetalated polysaccharide reverts to its native hydrophilic form,
which triggers the disassembly of micellar nanoparticles and the release
of the encapsulated prodrug. The conjugated HRP further activates
the prodrug by oxidation of IAA into cytotoxic radicals, which leads
to cellular apoptosis. The results indicate that the HRP–AcDex
conjugate in combination with IAA has great potential to be used as
a novel enzyme prodrug therapy for cancer treatment