Biological evaluation of lanthanide-based near-infrared imaging agents for the specific recognition of HER2 protein in a breast cancer model

master's thesis

• Title (croatian): Biološka procjena agenasa temeljenih na lantanidima u bliskom infracrvenom području za specifično prepoznavanje HER2 proteina u modelu raka dojke
• Author: Petra Ćutuk
• Mentor: Igor Stuparević (mentor)
• Committee member: Višnja Besendorfer (član povjerenstva)
• Committee member: Bojan Žunar (član povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Chemistry and Biochemistry); (Laboratory for Biochemistry); Zagreb
• Defense date and country: 2023-07-03, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Breast cancer (BC) is one of the most common malignancies worldwide and a leading cause of death among women. The HER2 positive breast cancer (overexpressing HER2 receptor) represents a very aggressive subtype and constitutes 15-20% of BC cases. Here we report about the creation of new diagnostic tool based on polystyrene beads incorporating Ln-based metallacrowns that were biologically targeted in a reaction of conjugation with Trastuzumab (Trz). The bioconjugation reaction was performed under various conditions. The resultinganti-HER2 conjugated beads were tested in vitro in studies of affinity, cytotoxicity and proliferation. We managed to do successful bioconjugation of Trz to polystyrene beads under optimized conditions. The conjugated compound exhibited preserved binding affinity for HER2 and showed specific interactions with HER2- overexpressing cells, the conjugate did not display extensive cytotoxic effects but inhibited the proliferation of HER2-overexpressing cells. These findings suggest the potential of Trz-beads as a targeted diagnostic tool for HER2-positive breast cancer.

Abstract (croatian)

Rak dojke (BC) jedna je od najčešćih zloćudnih bolesti u svijetu i vodeći uzrok smrti kod žena. HER2 pozitivan rak dojke (prekomjerna ekspresija HER2 receptora) predstavlja vrlo agresivan podtip i čini 15-20% slučajeva raka dojke. U ovom diplomskom radu se izvještava o razvoju dijagnostičkog alata temeljenog na polistirenskim kuglicama koje sadrže „metallacrowns“ na bazi lantanida na koje je vezan trastuzumab (Trz) u reakciji biološke konjugacije. Dobivene anti-HER2 konjugirane kuglice testirane su in vitro u studijama afiniteta, citotoksičnosti i proliferacije. Konjugirani spoj pokazao je očuvani afinitet vezanja za HER2 protein i specifične interakcije sa stanicama s prekomjernom ekspresijom HER2, bez značajnijeg citotoksičnog učinka dok inhibira proliferaciju stanica s prekomjernom ekspresijom HER2 receptora. Ovi nalazi sugeriraju potencijal Trz-kuglica kao ciljanog dijagnostičkog alata za HER2- pozitivan rak dojke.

• Keywords: breast cancer; HER2 receptor; bioconjugation; polystyrene beads; metallacrown; Trastuzumab; lanthanide; near-infrared; nanotechnology
• Keywords (croatian): rak dojke; HER2 receptor; biokonjugacija; polistirenske kuglice; „metalacrowns“; trastuzumab; lantanidi; blisko infracrveno područje; nanotehnologija
• Language: english
• URN:NBN: urn:nbn:hr:159:426569
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-05-16 08:32:58