The ability to accurately identify small cancerous cell deposits remains an ongoing clinical challenge. While conventional fluorescent labeling has been widely investigated, it suffers from needing an ultraviolet excitation. Such an excitation leads to low penetration depth and high autofluorescent background noise. Consequently, tremendous research effort has gone into producing the next generation of imaging agents, among which upconverting nanoparticles  (UCNPs) are particularly promising. These inorganic nanoparticles possess the ability to transform near-infrared light into visible light, thereby achieving significantly higher signal to noise when compared to the standard, down-converting fluorescent dyes. Additionally, UCNPs do not blink nor photobleach.<br/>In this work, we combine these UCNPs with plasmonic gold nanorods (AuNR) to create a multifunctional nanocluster that can selectively image and thermally ablate bladder cancer cells. The nanoclusters were created via two steps. First, water-dispersible UCNPs were conjugated to AuNRs using poly(ethylene) glycol via thiol-Au covalent bonding. Next, an antibody to epidermal growth factor receptor (EGFR) was conjugated to the UCNP surface via carbodiimide chemistry to direct the particles to the differentially expressed EGFR on the cancer cell surface. Bladder cancer cells were then incubated with the nanoclusters and imaged. Nanocluster formation was confirmed via electron microscopy, and selective binding to cancer cells was confirmed via live-cell, 2 photon imaging. Thermal ablation was achieved via irradiation with a laser tuned to the plasmon resonance of the AuNRs. Selective killing of EGFR-expressing cancer cells was verified by cell viability assay. Furthermore, we have demonstrated fluorescence detection and thermal ablation in human bladder tissues, showing the feasibility for the eventual clinical application of this approach. The multifunctional nanocluster represents a new paradigm of bladder cancer early detection and treatment that could potentially transform how bladder cancers are treated.

Multifunctional nanoclusters for simultaneous imaging and photothermal therapy of bladder cancer

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.