Nanoprobe Based on Biominerals in Protein Corona for Dual-Modality MR Imaging and Therapy of Tumors.

Various functional nanomaterials have been fabricated as diagnostic and therapeutic nanomedicines; however, the nanoparticles closely interact with proteins when immersed in biological fluids, forming a "protein corona" that critically alters the biological identity of nanomedicine. Here, we developed a robust strategy to construct theranostic nanoprobes based on protein-corona-coated Fe3 O4 nanoparticles and biomineralization in the corona. Water-soluble carboxylic Fe3 O4 nanoparticles were prepared by treating oleate-capped Fe3 O4 nanoparticles with Lemieux-von Rudloff reagent. Bovine serum albumin (BSA) was used as a model protein to form a corona on the surface of Fe3 O4 nanoparticles, endowing the Fe3 O4 nanoparticles with biocompatibility and nonimmunogenicity. The protein corona also provides a template for biomimetic mineralization of Fe3+ with tannic acid (TA) to construct Fe3 O4 @BSA-TAFeIII nanoprobes. The TA-Fe(III) biominerals can not only act as photothermal therapy agents but also interact with unsaturated transferrin in plasma to form a "hybrid" corona, enabling the nanoprobes to target tumor cells through the mediation of transferrin receptors, which commonly overexpress on tumor cell membranes. Once taken in by tumor cells, the protonation of phenol hydroxyl groups in acidic lysosomes would lead to the release of Fe3+ , inducing tumor cell death through a ferroptosis/apoptosis hybrid pathway. In addition, the released Fe3+ can boost the T 1 -weighted MR imaging performance, and the Fe3 O4 nanoparticles serve as T 2 -weighted MR imaging contrast agents. It is thus believed that the current nanoprobes can realize the enhanced dual-modality MR imaging and combined therapy of tumors through controlling the protein corona and biomineralization.