Targeted CuFe₂O₄ hybrid nanoradiosensitizers for synchronous chemoradiotherapy

Multifunctional nanoplatforms based on novel bimetallic nanoparticles have emerged as effective radiosensitizers owing to their potential capability in cancer cells radiosensitization. Implementation of chemotherapy along with radiotherapy, known as synchronous chemoradiotherapy, can augment the treatment efficacy. Herein, a tumor targeted nanoradiosensitizer with synchronous chemoradiotion properties, termed as CuFe₂O₄@BSA-FA-CUR, loaded with curcumin (CUR) and modified by bovine serum albumin (BSA) and folic acid (FA) was developed to enhance tumor accumulation and promote the anti-cancer activity while attenuating adverse effects. Both copper (Cu) and iron (Fe) were utilized in the construction of these submicron scale entities, therefore strong radiosensitization effect is anticipated by implementation of these two metals. The structure-function relationships between constituents of nanomaterials and their function led to the development of nanoscale materials with great radiosensitizing capacity and biosafety. BSA was used to anchor Fe and Cu ions but also to improve colloidal stability, blood circulation time, biocompatibility, and further functionalization. Moreover, to specifically target tumor sites and enhance cellular uptake, FA was conjugated onto the surface of hybrid bimetallic nanoparticles. Finally, CUR as a natural chemotherapeutic agent was encapsulated into the developed bimetallic nanoparticles. With incorporation of all abovementioned stages into one multifunctional nanoplatform, CuFe₂O₄@BSA-FA-CUR is produced for synergistic chemoradiotherapy with positive outcomes. In vitro investigation revealed that these nanoplatforms bear excellent biosafety, great tumor cell killing ability and radiosensitizing capacity. In addition, high cancer-suppression efficiency was observed through in vivo studies. It is worth mentioning that co-use of CuFe₂O₄@BSA-FA-CUR nanoplatforms and X-ray radiation led to complete tumor ablation in almost all of the treated mice. No mortality or radiation-induced normal tissue toxicity were observed following administration of CuFe₂O₄@BSA-FA-CUR nanoparticles which highlights the biosafety of these submicron scale entities. These results offer powerful evidence for the potential capability of CuFe₂O₄@BSA-FA-CUR in radiosensitization of malignant tumors and opens up a new avenue of research in this area.