Abstract
Bispecific T-cell engager (BiTE) immunotherapy is a promising therapy for cancer treatment. However, the high cost and short life-time in vivo of the BiTE limit its wide clinical application. Here, we built for the first time a gene delivery system based on MIL-88A metal organic framework nanoparticles and minicricle DNA (MOF/MC) to realize high-efficient in vivo expression of anti-CD3/anti-EpCAM BiTE. X-ray photoelectron spectroscopy (XPS) and dynamic light scattering (DLS) analysis verified that MC molecules were loaded onto MOF nanoparticles through metal-phosphate bonds and electrostatic interactions. It is found that intraperitoneal injection (i.p.) of MOF/MC suspensions showed good transfection performance in mice abdominal cavity with low toxicity. In an intraperitoneal xenograft mice model established using SKOV3 ovarian cells, i.p. injection of MOF/MC.BiTE significantly inhibited tumor growth and prolonged the average survival time of the mice. Overall, our study demonstrates a simple and highly efficient MOF-based gene delivery system holding promise for effective ovarian cancer immunotherapy.
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