Therapeutic nucleus-access BNCT drug combined CD47-targeting gene editing in glioblastoma

• DOI: 10.1186/s12951-022-01304-0
• Publication Date: 2022-03-04T05:02:24Z
• Authors: Jiejian Chen; Qi Dai; QiYao Yang; Xiaoyan Bao; Yi Zhou; Haiqing Zhong; Linjie Wu; Tiantian Wang; Zhicheng Zhang; Yiying Lu; Zhentao Zhang; Mengting Lin; Min Han; Qichun Wei
• Keywords: Gene Editing; 0301 basic medicine; 0303 health sciences; Brain Neoplasms; Research; Boron Neutron Capture Therapy; CD47 Antigen; Glioma; 3. Good health; Boron agent; Boron neutron capture therapy; Mice; 03 medical and health sciences; Pharmaceutical Preparations; Medical technology; Animals; R855-855.5; CD47; Glioblastoma; Nanoliposome; TP248.13-248.65; Nucleus-targeting; Biotechnology

Glioblastoma is the most common brain primary malignant tumor with highest mortality. Boron neutron capture therapy (BNCT) can efficiently kill cancer cells on cellular scale, high accuracy, short course and low side-effects, which regarded as promising for tumors like glioma. As keypoint of BNCT, all boron delivery agents currently in clinical use are beset by insufficient uptake, especially nucleus, limits application BNCT. In this study, nuclear targeting achieved DOX-CB, consisting doxorubicin (DOX) carborane (CB) utilizing translocation property DOX. The nucleus GL261 takes up almost three times concentration required To further glioma inhibit recurrence, a new multifunctional nanoliposome system DOX-CB@lipo-pDNA-iRGD constructed. It combines DOX-CB immunotherapy strategy blocking macrophage immune checkpoint pathway CD47-SIRPα CRISPR-Cas9 system, coupling BNCT simultaneously. Compared drug Borocaptate Sodium (BSH), significantly enhances survival rate tumor-bearing mice, reduces stemness, improves prognosis. excellent curative effect provides an insight into combined treatment