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Cellular uptake of metallated cobalamins
Mai Thanh Quynh Tran1, Stefan Stürup2, Ian Henry Lambert3
1Institute of Inorganic Chemistry, University of Zürich, Winterthurerstr. 190, 8057 Zürich, Switzerland. ariel@aci.uzh.ch.
Metallomics : Integrated Biometal Science
|January 8, 2016
Summary
Vitamin B12-cisplatin conjugates deliver cisplatin into cells, with charged versions showing enhanced uptake via additional pathways. This research explores novel drug delivery for cancer therapy.
Area of Science:
- Biochemistry
- Pharmacology
- Nanotechnology
Background:
- Vitamin B12 is crucial for cellular processes.
- Cisplatin is a widely used chemotherapy drug.
- Targeted drug delivery aims to improve cancer treatment efficacy and reduce side effects.
Purpose of the Study:
- To investigate the cellular uptake of vitamin B12-cisplatin conjugates.
- To compare the delivery efficiency of B12-cisplatin conjugates with free cisplatin.
- To explore potential additional cellular uptake pathways for charged B12 derivatives.
Main Methods:
- Cellular uptake studies using inductively coupled plasma mass spectrometry (ICP-MS) to detect metal constituents (Co, Pt, Re).
- Comparison of uptake for neutral and charged vitamin B12 derivatives, including controls like cyano-cob(iii)alamin and aquo-cob(iii)alamin.
- Assessment of B12 derivative affinities to B12 transporters (HC, IF, TC).
Main Results:
- Vitamin B12-cisplatin conjugates delivered cisplatin to cellular cytosol and nuclei with approximately one-third the efficiency of free cisplatin.
- Charged B12 derivatives exhibited significantly higher cellular uptake compared to neutral B12.
- Charged B12 derivatives showed similar affinities to B12 transporters as native vitamin B12, suggesting an additional internalization mechanism.
Conclusions:
- Vitamin B12-based conjugates can serve as carriers for cisplatin delivery into cancer cells.
- The charge of B12 derivatives influences their cellular uptake, indicating the involvement of specific transport mechanisms beyond the native B12 pathway.
- These findings support the potential of developing charged vitamin B12 conjugates for targeted cancer chemotherapy.
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