Mesenchymal stem cells(MSCs)are promising vehicles for the delivery of anticancer agents in cancer therapy.However,the tumor targeting of loaded therapeutics is essential.Here,we explored a dual-targeting strategy to incorporate tumortropic MSC delivery with HER2-specific killing by the immunoapoptotin e23sFv-Fdt-tBid generated in our previous studies.The MSC engineering allowed simultaneous immunoapoptotin secretion and bioluminescence detection of the modified MSCs.Systemic administration of the immunoapoptotin-engineered MSCs was investigated in human HER2-reconstituted syngeneic mouse models of orthotopic and metastatic breast cancer,as well as in a xenograft nude mouse model of orthotopic gastric cancer.In vivo dual tumor targeting was confirmed by local accumulation of the bioluminescence-imaged MSCs and persistence of His-immunostained immunoapoptotins in tumor sites.The added tumor preference of MSC-secreted immunoapoptotins resulted in a significantly stronger antitumor effect compared with purified immunoapoptotins and Jurkatdelivered immunoapoptotins.This immunoapoptotin-armored MSC strategy provides a rationale for its use in extended malignancies by combining MSC mobility with redirected immunoapoptotins against a given tumor antigen.