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 Fe 3 O 4 nanoparticles and biomineralization in the corona. Water-soluble carboxylic Fe 3 O 4 nanoparticles were prepared by treating oleate-capped Fe 3 O 4 nanoparticles with Lemieux-von Rudloff reagent. Bovine serum albumin (BSA) was used as a model protein to form a corona on the surface of Fe 3 O 4 nanoparticles, endowing the Fe 3 O 4 nanoparticles with biocompatibility and nonimmunogenicity. The protein corona also provides a template for biomimetic mineralization of Fe 3+ with tannic acid (TA) to construct Fe 3 O 4 @BSA-TAFe III 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 Fe 3+ , inducing tumor cell death through a ferroptosis/apoptosis hybrid pathway. In addition, the released Fe 3+ can boost the T 1 -weighted MR imaging performance, and the Fe 3 O 4 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.