Objective To prepare a rapamycin(RAPA)-loaded core-shell pH-sensitive drug delivery system and investigate its effect on breast cancer cells in vitro.Methods Mesoporous silica nanoparticles(MSNs)encapsulated by liposomes were prepared using the sol-gel method,and RAPA was loaded after the MSNs were amino modified.Rapamycin-loaded mesoporous silica nanoparticles core-lipid shell nanoplatform(RAPA-MSN-LN)was prepared by thin-film dispersion method,and their encapsulation efficiency,morphology,particle size,potential,stability and release behavior were evaluated.Breast cancer cells MCF-7 and 4T1 were used as models,and the inhibitory effect of RAPA-MSN-LN on the growth of breast cancer cells was detected by the methyl thiazolyl tetrazolium method and the effect of RAPA-MSN-LN on cell apoptosis was analyzed by flow cytometry.Results RAPA-MSN-LN was successfully prepared.The encapsulation efficiency of RAPA was(48.92±1.50)%,the average particle size was(98.12±1.80)nm,the polydispersity index was 0.146±0.013,and the potential was(-18.4±1.2)mV.The stability observation showed that RAPA-MSN-LN was stable at 4,25,and 37℃ and in serum.The results of the release experiment in vitro showed that RAPA-MSN-LN had significant pH-sensitivity.The results of the anti-tumor experiment in vitro showed that RAPA-MSN-LN could effectively inhibit the growth of breast cancer cells MCF-7 and 4T1 and induce their apoptosis.Conclusion RAPA-MSN-LN has high encapsulation efficiency,pH-sensitivity and good anti-tumor effect in vitro.