Modular Synthesis of Semiconducting Graft Copolymers to Achieve "Clickable" Fluorescent Nanoparticles with Long
Adam Creamer1, Alessandra Lo Fiego1, Alice Agliano1
1Department of Materials, Department of Bioengineering, Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Advanced Materials (Deerfield Beach, Fla.)
|March 11, 2023
Summary
Researchers developed stable semiconducting polymer nanoparticles (SPNs) for cancer theranostics. These nanoparticles target HER2-positive cancer cells, showing potential for improved diagnostics and therapeutics.
Area of Science:
- Nanotechnology
- Biomaterials
- Cancer Research
Background:
- Semiconducting polymer nanoparticles (SPNs) offer promise for cancer theranostics due to their optical properties and biocompatibility.
- However, SPNs face challenges with aggregation and protein fouling in biological environments, limiting their in vivo efficacy.
- Developing stable and targeted SPNs is crucial for advancing cancer theranostic applications.
Purpose of the Study:
- To create colloidally stable and low-fouling semiconducting polymer nanoparticles (SPNs).
- To functionalize SPNs for targeted delivery to HER2-positive cancer cells.
- To evaluate the in vivo performance and targeting capabilities of the developed SPNs for cancer theranostics.
Main Methods:
- Grafting poly(ethylene glycol) (PEG) onto semiconducting polymer backbones via a one-step postpolymerization substitution reaction.
- Site-specific conjugation of targeting ligands (antibodies, antibody fragments, affibodies) to PEGylated SPNs using click chemistry.
- In vivo evaluation of PEGylated SPN circulation in zebrafish embryos and targeting of HER2-expressing cancer cells in a zebrafish xenograft model.
Main Results:
- Achieved colloidally stable and low-fouling SPNs by covalent PEGylation.
- Demonstrated successful site-specific attachment of HER2-targeting moieties to the SPN surface.
- Observed excellent long-term circulation (up to 7 days) of PEGylated SPNs in zebrafish embryos.
- Confirmed specific targeting of HER2-positive cancer cells by affibody-functionalized SPNs in a zebrafish xenograft model.
Conclusions:
- The developed covalent PEGylated SPN system enhances colloidal stability and reduces fouling for in vivo applications.
- Site-specific functionalization enables targeted delivery to cancer cells, improving theranostic potential.
- These advanced SPNs show significant promise for the development of next-generation cancer theranostics.
