Peptide Decorated Multinuclear Lanthanide Architectures for Dual Imaging and Delivery Applications
Lead Research Organisation:
University of Manchester
Department Name: Chemistry
Abstract
Short peptides, comprising of 8-40 amino acids, are increasingly being used to deliver payloads through cell membranes and to specific subcellular compartments (ACSNano, 2014, 8, 1972). This project will utilize known conjugation strategies (Analyst, 2010, 135, 42) to append peptides of defined sequences to luminescent, self-assembling Ln3+ architectures, thus providing a strategy to simultaneously control and visualize cellular localization of a delivery vehicle, and hence payload.
The PhD student assigned to this project will synthesize and characterize a selection of lanthanide and mixed lanthanide-transition metal complexes; the coordination motifs that endow the best aqueous stability and imaging properties (i.e. quantum yield and lifetime) will then be incorporated into metal organic constructs functionalized with pendant peptide sequences known to localize to specific intracellular organelles. Cellular uptake and localization will be evaluated, to ensure the cellular localization properties of the peptide are retained once conjugated to the lanthanide complex. The final stage of this project will then be to tailor the capsules for specific guest molecules with known pharmaceutical activity.
Objectives
1) Develop supramolecular chemistry of lanthanides to enable construction of water-soluble architectures with internal void pockets.
2) Evaluate spectroscopic properties of constructs to identify the best systems for lanthanide imaging.
3) Develop protocol for appending peptides to supramolecular architectures (transition metal and lanthanide constructs), enabling cell penetration and organelle targeting.
4) Evaluate cellular uptake and imaging properties of architectures, in the presence/absence of a guest.
Currently small lanthanide based architectures that are water-soluble are known, however these lack the capacity to carry a guest molecule. Larger lanthanide based structures that can accommodate guest molecules have found application as novel sensors, but these structures are insoluble or unstable in aqueous environments. This research will identify structural motifs that support both aqueous solubility and guest incorporation with an aim to develop novel drug delivery vehicles with inherent luminescence enabling them to be tracked in cells.
The student will receive interdisciplinary training as they synthesize and characterize novel organic ligands and metal-organic complexes, perform extensive spectroscopic studies on the lanthanide complexes and analyze the cellular uptake of the complexes.
The PhD student assigned to this project will synthesize and characterize a selection of lanthanide and mixed lanthanide-transition metal complexes; the coordination motifs that endow the best aqueous stability and imaging properties (i.e. quantum yield and lifetime) will then be incorporated into metal organic constructs functionalized with pendant peptide sequences known to localize to specific intracellular organelles. Cellular uptake and localization will be evaluated, to ensure the cellular localization properties of the peptide are retained once conjugated to the lanthanide complex. The final stage of this project will then be to tailor the capsules for specific guest molecules with known pharmaceutical activity.
Objectives
1) Develop supramolecular chemistry of lanthanides to enable construction of water-soluble architectures with internal void pockets.
2) Evaluate spectroscopic properties of constructs to identify the best systems for lanthanide imaging.
3) Develop protocol for appending peptides to supramolecular architectures (transition metal and lanthanide constructs), enabling cell penetration and organelle targeting.
4) Evaluate cellular uptake and imaging properties of architectures, in the presence/absence of a guest.
Currently small lanthanide based architectures that are water-soluble are known, however these lack the capacity to carry a guest molecule. Larger lanthanide based structures that can accommodate guest molecules have found application as novel sensors, but these structures are insoluble or unstable in aqueous environments. This research will identify structural motifs that support both aqueous solubility and guest incorporation with an aim to develop novel drug delivery vehicles with inherent luminescence enabling them to be tracked in cells.
The student will receive interdisciplinary training as they synthesize and characterize novel organic ligands and metal-organic complexes, perform extensive spectroscopic studies on the lanthanide complexes and analyze the cellular uptake of the complexes.
Organisations
People |
ORCID iD |
| Imogen Anne Riddell (Primary Supervisor) | |
| Daniel Bell (Student) |