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Published on: February 8, 2017
A Cell Membrane Targeting Molybdenum-Iodine Nanocluster: Rational Ligand Design toward Enhanced Photodynamic Activity
Kaplan Kirakci1, Michaela Kubáňová2, Tomáš Přibyl2
1Institute of Inorganic Chemistry of the Czech Academy of Sciences, Řež 1001, 250 68 Husinec-Řež, Czech Republic.
Abstract:
The development of singlet oxygen photosensitizers, which target specific cellular organelles, constitutes a pertinent endeavor to optimize the efficiency of photodynamic therapy. Targeting of the cell membrane eliminates the need for endocytosis of drugs that can lead to toxicity, intracellular degradation, or drug resistance. In this context, we utilized copper-free click chemistry to prepare a singlet oxygen photosensitizing complex, made of a molybdenum-iodine nanocluster stabilized by triazolate apical ligands. In phosphate-buffered saline, the complex formed nanoaggregates with a positive surface charge due to the protonatable amine function of the apical ligands. These nanoaggregates targeted cell membranes and caused an eminent blue-light phototoxic effect against HeLa cells at nanomolar concentrations, inducing apoptotic cell death, while having no dark toxicity at physiologically relevant concentrations. The properties of this complex were compared to those of a negatively charged parent complex to highlight the dominant effect of the nature of apical ligands on biological properties of the nanocluster. These two complexes also exerted (photo)antibacterial effects on several pathogenic strains in the form of planktonic cultures and biofilms. Overall, we demonstrated that the rational design of apical ligands toward cell membrane targeting leads to enhanced photodynamic efficiency.
Insights
We developed novel molybdenum-iodine nanoclusters as singlet oxygen photosensitizers for photodynamic therapy. These targeted cell membranes, showing potent blue-light phototoxicity against cancer cells and bacteria with minimal dark toxicity.
Area of Science:
- Photodynamic Therapy
- Nanomaterials
- Singlet Oxygen Sensitizers
Background:
- Optimizing photodynamic therapy (PDT) requires efficient singlet oxygen (SO) photosensitizers targeting specific cellular organelles.
- Cell membrane targeting circumvents issues associated with endocytosis, such as drug resistance and intracellular degradation.
- Developing novel photosensitizers with enhanced targeting capabilities is crucial for advancing PDT efficacy.
Purpose of the Study:
- To design and synthesize a novel singlet oxygen photosensitizing complex utilizing copper-free click chemistry.
- To investigate the cellular uptake, phototoxicity, and antibacterial activity of the developed complex.
- To evaluate the impact of apical ligand design on the biological properties and therapeutic efficacy of molybdenum-iodine nanoclusters.
Main Methods:
- Synthesis of a molybdenum-iodine nanocluster stabilized by triazolate apical ligands using copper-free click chemistry.
- Characterization of nanoaggregate formation and surface charge in phosphate-buffered saline.
- Assessment of blue-light induced phototoxicity against HeLa cells and antibacterial effects on pathogenic strains (planktonic and biofilm).
Main Results:
- The positively charged nanoaggregates effectively targeted cell membranes, inducing apoptotic cell death in HeLa cells at nanomolar concentrations via blue-light irradiation.
- No significant dark toxicity was observed at physiologically relevant concentrations.
- Both planktonic and biofilm cultures of pathogenic bacteria exhibited phototoxic effects upon treatment with the developed complexes.
Conclusions:
- Rational design of apical ligands enables targeted delivery to cell membranes, significantly enhancing photodynamic efficiency.
- The developed molybdenum-iodine nanocluster complex represents a promising platform for photodynamic therapy and antimicrobial applications.
- Surface charge and ligand properties play a dominant role in the biological activity and therapeutic potential of these nanoclusters.
