摘要
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.
基金
This study was supported by the Interdisciplinary Program of Shanghai Jiao Tong University(ZH2018ZDA18)
We are grateful for the support of ECNU Multifunctional Platform for Innovation(011),and the Flow Cytometry Core Facility at ECNU.