Circulating Tumour Cells-Targeting Au-Nanocages-Mediated Bimodal Phototherapeutic Properties Enriched by Magnetic Nanocore
Metastasis resulting from circulating tumor cells (CTCs) is associated with 90% of all cancer mortality. To disrupt cancer dissemination, therapeutic targeting of CTCs by extracorporeal photodynamic therapy (PDT) has emerged but remain impractical due to limited therapeutic window. Herein, we developed a targeted photosensitive and magnetic core-satellite nanomedicine (TCSN) to augment the light-induced damage to targeted cells. The magnetic core (MNC) with multiple iron oxide nanoparticle stablized using thiolated polyvinyl alcohol can magnetize CTCs to achieve magnetic enrichment under magnetic field. Multiple gold nanocages (AuNCs) satellites were conjugated on MNC to facilitate bimodal photothermal therapy and PDT. Adjusting the thiol content in MNC allows the manipulation of AuNCs density on TCSN, which was found to demonstrate a density-dependent bimodal phototherapeutic effect under the of 808 nm and 940 nm laser irrdaiation. Moreover, with the immobilization of anti-epithelial cell adhesion molecule (anti-EpCAM), TCSN exploited enhanced affinity toward EpCAM-expressive 4T1 cells. We demonstrate that theTCSN-labelled 4T1 cells can be isolated and photoeradicated in a microfluidic channel with a dynamic flow. Our studies showed TCSN with the complementary properties of MNC and AuNCs can largely augment the therapeutic window by magnetic enrichement and bimodal phototherapy, serveing as an advanced extracorporeal strategy to remove CTCs.