Pulmonary
metastasis of
breast cancer is the major cause of deaths of
breast cancer patients, but the effective treatment of pulmonary
metastases is still lacking at present. Herein, a degradable biomimetic
DNAzyme biocapsule is developed with the poly(
ethylenimine) (PEI)-
DNAzyme complex encapsulated in a Mn2+/Zn2+-coordinated
inositol hexaphosphate (IP6)
capsule modified with the cRGD targeting
peptide for high-efficiency gene therapy of both primary and pulmonary metastatic
breast tumors. This
DNAzyme biocapsule is degradable inside acidic lysosomes, leading to the release of
DNAzyme and abundant Mn2+/Zn2+ for catalytic cleavage of EGR-1
mRNA. We find that PEI promotes the lysosomal escape of the released
DNAzyme. Both in vitro and in vivo experiments demonstrate the apparent downregulation of EGR-1 and Bcl-2
protein expression
after treatment with the
DNAzyme biocapsule, thereby inducing apoptotic death of
tumor cells. We further verify that the
DNAzyme biocapsule exhibits potent therapeutic efficacy against both primary and pulmonary metastatic
breast tumors with significant inhibition of peri-pulmonary
metastasis. This study provides a promising effective strategy for constructing degradable
DNAzyme-based platforms with self-supply of abundant
metal ion cofactors for high-efficiency gene therapy of metastatic
breast cancer.