Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

BACKGROUND:Cerebral vascular malformations are the leading cause of hemorrhagic apoplexy in young adults, and the rupture and bleeding of malformed vessels may cause severe neurological dysfunction. The mechanism of cerebral vascular malformations remains unclear. Modern molecular biology studies have shown that, angiogenic growth factors are abnormal y expressed in cerebral vascular malformations.
OBJECTIVE:To evaluate differences in the expression of angiogenic growth factors in cerebral vascular malformations, and discuss the possible relationship between cerebral vascular malformations and angiogenic growth factors.
METHODS:Fifty patients with cerebral vascular malformations and fifty patients with intracerebral hemorrhage were included in this study. The expressions of angiogenic growth factor (vascular endothelial growth factor and transforming growth factor-α) in the cerebral vascular malformation specimens and the normal superficial temporal artery specimens were detected with immunohistochemical staining.
RESULTS AND CONCLUSION:In the normal superficial temporal artery of intracerebral hemorrhage patients, no expression of vascular endothelial growth factor and transforming growth factor-αwas found;in the vascular malformations, they were highly expressed (P<0.05). Compared with normal blood vessels, vascular endothelial growth factor and transforming growth factor-αexpression was significantly increased in patients with cerebral vascular malformations.