Study Of Nuclear-targeted Nano Delivery System Inhibits Growth Of Breast Cancer Stem Cell

Cancer stem cells(CSCs)are a small of cells that exhibit distinctive self-renewal,proliferation and differentiation capabilities,which are believed to play a crucial role in tumour progression,drug resistance,recurrence and metastasis in multiple malignancies.The existence of CSCs is a primary obstacle to cancer therapy,therefore the nano-drug delivery system for CSCs is one of the the hotspots of current research.At present,nano drug delivery-based approaches have great potential to solve the limitations chemotherapy treatment,such as poor water solubility,short cycle time and instability.However,the high drug resistance and drug efflux of CSCs,the currently targeted CSCs nano-drug delivery system has relatively low targeting efficiency and anti-cancer effect.Nucleus-targeted drug delivery is a promising strategy for reverse the drug resistance and drug efflux of CSCs,but in vivo nucleus-targeted drug delivery has been challenging.Herein,we designed a mesoporous silica nanoparticles(MSNs)-based nucleus-targeted system,which could directly target the BCSCs and further enter the nucleus by the surface modification of anti-CD133 and thermal-triggered exposure of TAT peptides under an alternating magnetic field(AMF).The nucleus-targeted drug release ultimately leads to an exhaustive apoptosis of the CSCs through combined thermotherapy and hypoxia-activated chemotherapy.In vivo and vitro,the nucleus-targeted nano delivery system efficiently inhibits the tumor growth without notable side effects during the course of treatment.Molecular mechanism study illustrates that the system effectively eliminates the CSCs by blocking the hypoxia signaling pathway.This designed nucleus-targeted nano delivyer system is expected to provide new insights for developing efficient platforms for CSC-targeted cancer therapy.