BSA-magnetite nanotorpedo for safe and efficient delivery of chemotherapy drugs

• The advantages of inorganic and protein carriers were achieved simultaneously. • The leakage problem of hydrophobic drug was effectively solved. • The structure-activity relationships of the nanotorpedo was deeply explained. Drug delivery system based on inorganic nanomaterials or protein carriers has the unique advantages in chemotherapy. With the increasing clinical demand for safer and more efficient drug delivery, combining the superiority of inorganic nanomaterials and protein carriers, which can be a feasible strategy to optimize the drug delivery system. In this work, we successfully designed a BSA-magnetite nanotorpedo (BMNT), which is composed of magnetite and doxorubicin (Dox) molecules encapsulated by a self-assembled nanocage of 6 bovine serum albumin (BSA) subunits. The nanotorpedo integrated the above two important drug delivery system by introducing the biomimetic synthesis strategy. The nanotorpedo effectively solved the leakage problem of hydrophobic drug molecules, and prolonged their half-life in blood circulation, achieving efficient antitumor efficacy. Furthermore, based on transmission electron microscope (TEM), molecular dynamics (MD) simulation and computational modeling, we proposed the complex structure of the nanotorpedo with protein-drug-nanoparticle composites. The results confirmed the structural basis for the encapsulating stability of doxorubicin, and shed light on understanding the structure-activity relationships of the nanotorpedo as a drug carrier, expanding the scope of the research in drug delivery system.