The treatment of malignant bone
tumors by chemotherapeutics often receives poor therapeutic response due to the specific physiological bone environment, and thus calls for the development of new therapeutic options. Here, we reported a bone-targeted
protein nanomedicine for this purpose.
Saporin, a toxin
protein, was co-assembled with a boronated
polymer for intracellular
protein delivery, and the formed nanoparticles were further coated with an anionic
polymer poly (
aspartic acid) to shield the positive charges on nanoparticles and provide the bone targeting function. The prepared ternary complex nanoparticles showed high bone accumulation both in vitro and in vivo, and could reverse the surface charge property from negative to positive after locating at
tumor site triggered by
tumor extracellular acidity. The boronated
polymer in the de-shielded nanoparticles further promote intracellular delivery of
saporin into
tumor cells, exerting the anticancer activity of
saporin by inactivation of ribosomes. As a result, the bone-targeted and
saporin-loaded nanomedicine could kill
cancer cells at a low
saporin dose, and efficiently prevented the progression of
osteosarcoma xenograft
tumors and bone metastatic
breast cancer in vivo. This study provides a facile and promising strategy to develop
protein-based nanomedicines for the treatment of malignant bone
tumors.