Targeted destruction of cancer stem cells using multifunctional magnetic nanoparticles that enable combined hyperthermia and chemotherapy

Cancer stem cells (CSCs) have been implicated in cancer recurrence and therapy resistance. Therefore,a CSC-targeted therapy that disrupts the maintenance and survival of CSCs may offer an effectiveapproach in killing tumor cells in primary tumors and preventing the metastasis caused by CSCs.Nanoparticles (NPs)-based thermotherapy and/or chemotherapy are promising therapeutic methods forcancer treatment. 
Methods: A silica-based multifunctional NP system was present, which encapsulated achemotherapeutic agent and magnetic cores and coated with a specific antibody against the lung CSCs.The efficacy of this novel therapeutic strategy was systematically studied both in vitro and in vivo bysimultaneous activating the combined thermotherapy and chemotherapy via CSC-targeted NPs. 
Results: These NPs were systematically administered and activated for targeted chemotherapy andthermotherapy by using an externally applied alternating magnetic field (AMF). The antibody-modifiedNPs targeted to lung CSCs with enhanced cellular uptake in vitro and extended accumulation in tumor invivo. Up to 98% of lung CSCs was killed in vitro with 30-min application of AMF, due to the combinedeffects of hyperthermia and chemotherapeutic drug treatment. In in vivo models, this combined therapysignificantly suppressed tumor growth and metastasis in lung CSC xenograft-bearing mice, with minimalside effects and adverse effects. 
Conclusion: With good biocompatibility and targeting capability, the nanodrug delivery system mayoffer a promising clinical platform for the combined thermotherapy and chemotherapy. This workdemonstrated the feasibility of developing multifunctional nanomedicine targeting CSCs for effectivecancer treatment.