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Carbohydrate-based nanomaterials for imaging and drug delivery


Varela-Aramburu,  Silvia
Peter H. Seeberger - Nanoparticles and Colloidal Polymers, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;
Peter H. Seeberger - Automated Systems, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Varela-Aramburu, S. (2018). Carbohydrate-based nanomaterials for imaging and drug delivery. PhD Thesis, Freie Universität, Berlin.

Cite as: https://hdl.handle.net/21.11116/0000-0002-D016-A
As glycans are exposed on the surface of living cells, they are instrumental in biological
processes such as cell-cell interactions, cell growth and cell differentiation. Multivalent
carbohydrate-based nanomaterials help clarify these processes by mimicking the biological
activity of carbohydrates. Moreover, nanomaterials have high potential for the imaging of
diseases or biological processes, and can be further engineered for controlled and targeted
drug delivery.
In the first part of this dissertation, a straightforward and robust room temperature one-pot
synthesis of ultrasmall gold nanoparticles (2 nm) was developed using thio-glucose as a
reducing and stabilizing agent (Chapter 2). The resultant monodisperse gold nanoparticles
showed high stability and could be further functionalized using two different conjugation
methods. These non-cytotoxic nanoclusters were radiolabeled for biodistribution studies in
vivo, showing accumulation in almost all organs and clearance after 24 h.
The developed ultrasmall glycosylated gold nanoparticles were utilized to target the
protozoan parasites Plasmodium falciparum and Toxoplasma gondii (Chapter 3). These
parasites contain cysteine-rich domains in their surface proteins and could potentially
capture gold nanoparticles through the well-known thiol-gold affinity. The gold
nanoparticles were able to efficiently bind all the blood stages of P. falciparum, and both
intracellular and extracellular T. gondii. Drug conjugation was performed for further in
vitro and in vivo inhibition studies.
Flat discoidal mesoporous silica nanoparticles were synthesized and their biological
applications were investigated (Chapter 4). These novel materials were internalized by
HeLa cancer cells and showed increased intracellular drug delivery as compared to
spherical analogues. Moreover, the introduction of cleavable disulfide moieties within the
mesoporous silica framework enabled investigation of the impact of increasing cleavable
bonds on the breakability and efficacy of these materials as nanovectors.
Multivalent glycosylated nanoparticles were synthesized to image biological processes
(Chapter 5). Ultrasmall fluorescent silicon nanoparticles were functionalized with glucose
and a radiotracer in order to study the blood brain barrier crossing in vivo. Also, plasmonic
gold nanoparticles were conjugated with a collection of carbohydrates for carbohydrateprotein
interactions studies between green algae and cyanobacteria.
In conclusion, the design and engineering of glycosylated nanoparticles allows mimicking
biological processes, obtaining unknown information through imaging techniques, and
producing targeted nanocarriers for controlled drug delivery.