Biomimetic Multifunctional Nanozyme Enhanced Radiosensitization For Breast Cancer Via X?ray Triggered Cascade Reaction

Breast cancer,one of the most common malignancies worldwide,is a major disease threatening women’s health.Current treatments for breast cancer are mainly surgery,radiotherapy,chemotherapy,in which surgical treatment is traumatic and difficult to eradicate,even in patients after curative treatment of breast cancer,there is still a high chance of recurrence.Chemotherapeutics,drug resistance in patients is a big challenge in the treatment of breast cancer.While radiotherapy is currently the treatment of choice for most patients,in clinical breast cancer patients generally combined with high-dose radiotherapy to improve the killing of tumor cells and reduce the possibility of recurrence,radiotherapy is widely used in the clinic for breast cancer treatment.But a large dose of radiation therapy is difficult to completely remove tumor tissues,especially tumor lesions with radiation resistance,and it also causes radiation damage to normal tissues.Therefore,how to improve the radiosensitivity of tumors and protect normal tissues from radiation damage is gaining more and more attention.In this subject study,we designed a novel biomimetic and multifunctional nanozyme(BSA@CeO/Fe²⁺),which was used as a radiosensitizer for breast cancer treatment.Nanosized ceria（CNPs）,as a new class of inorganic nanozymes,exhibit various biological activities and can be used as potential bioscaffolds for antioxidation,anti-aging,or regenerative medicine.Especially when two oxides,CeO₂（Ce⁴）and Ce₂O₃(Ce³⁺),coexist on the surface of nanomaterials,the interchangeability of this valence state enables sustainable catalytic performance of CNPs,which is expected to further play a role in biomedical applications.However,nanoparticles with low biocompatibility are easily agglomerated and can be easily phagocytosed and cleared by macrophages and the reticuloendothelial system（ERS）in the body,which significantly decreases their biological activity,and the massive hepatic accumulation will also lead to increased biological toxicity.Therefore,CNPs also need biocompatible modification of their surface before their use in radiation sensitization studies.BSA modified nanomaterials not only have better dispersion and biocompatibility,but also are favorable for the further modification of subsequent functional ligands.Using this feature,the modification of BSA to ultrasmall nanozyme CNPs can further improve their biocompatibility.The results showed that:BSA@CeO/Fe²⁺is pH dependent thereby possesses multiple enzymatic activities,which elevates the hydroxyl radical（·OH）level via a cascade catalytic reaction under the tumor microenvironment to obtain the desired tumor inhibition rate（83.07%）.Meanwhile,BSA@CeO/Fe²⁺has also been shown to reduce reactive oxygen species（ROS）levels in normal cells.Additionally,Routine blood tests and blood biochemical tests of BSA@CeO/Fe²⁺nanozymes showed no significant toxicity.Therefore,biomimetic nanozymes BSA@CeO/Fe²⁺with multiple enzymatic activities have been rationally designed in this work,while achieving high radiotherapy efficacy and excellent biosafety,this study provides a possible clinical practical strategy for nanozymes to be used in tumor therapy.