Membrane-coated Nanoparticles For The Treatment Of Stress-escaped Cancer Stem Cells

Cancer stem cells(CSCs)are a small number of cells with unlimited proliferation,self-renewal and multilineage differentiation in tumor tissue.Under the stimulation of traditional cancer treatment strategies(chemotherapy,radiotherapy,hyperthermia,surgery,etc.),a little number of CSCs will survive by escaping external stress,which are called Stress Escape Cancer Stem Cells(SECSCs).SECSCs not only retain the properties of CSCs,but also have stronger ability of sphere formation,invasion and metastasis,and tumorigenicity in vitro or in vivo.The existence of SECSCs is the main reason of cancer recurrence and metastasis.Effectively targeting SECSCs and inhibiting their proliferation and metastasis is the most urgent problem to treat cancer.In this paper,firstly,we constructed a SECSCs model,and screened and isolated SECSCs successfully.As showing by in vitro and in vivo experiments,SECSCs are the main cause of recurrence and metastasis.Secondly,a biomimetic magnetic nano drug(BMNPs)was designed and synthesized,which can homologously target SECSCs and inhibit their proliferation and metastasis.Finally,it was evaluated that BMNPs have excellent anti-tumor activity by in vitro and in vivo experiments.BMNPs were coated with a layer of mesoporous silica with magnetic mesoporous silicon nanoparticles(FMSN)as the core,and loaded with the chemotherapy drug docetaxel(DTX).The surface of the nanoparticles was camouflaged with SECSCs cell membrane by cell membrane camouflage technology.BMNPs have excellent properties such as high biocompatibility,long circulation cycle,immune escape and homologous targeting.BMNPs not only avoid the toxic side effects caused by the non-specific early release of DTX,but also increase the enrichment of nanomedicine in tumor tissues by efficiently homologous target ability.Under the action of alternating magnetic field(AMF),BMNPs induce apoptosis of SECSCs and inhibit proliferation and metastasis of SECSCs in vitro and in vivo through the combination of chemotherapy(DTX)and magnetic hyperthermia(FMSN).The viewpoint of SECSCs provides an important way to overcome the difficult problem of cancer in clinic.The successful development of BMNPs and the good antitumor activity and high biocompatibility have far-reaching application prospects in clinical anticancer treatment.