1. State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, P. R. China
2. University of Chinese Academy of Sciences, 100049 Beijing, P. R. China
3. Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P. R. China
4. National Engineering Research Center for Nanotechnology, Shanghai 200241, P. R. China
Rationale: Ferritin with unique hollow cavity is an emerging protein-based nanoplatform for anticancer-drug delivery, but the in vivo chemotherapeutic effectiveness is still unsatisfactory with such a monotherapy modality, which is urgently in need of improvement.
Methods: Here a novel ferritin nanotheranostic with anticancer-drug doxorubicin encapsulated into its hollow interior and nanoradiosensitizer bismuth sulfide nanocrystals inlayed onto its polypeptide shell was synthesized for combinational therapeutic benefits. The formation mechanism of bismuth sulfide nanocrystals based on ferritin has been analyzed. The in vitro and in vivo treatment effects were carried out on HeLa cancer cells and tumor-bearing mice, respectively. The biocompatibility and excretion of the ferritin nanotheranostic have also been evaluated to guarantee their biosafety.
Results: The polypeptide shell of ferritin provides nucleation sites for the bismuth sulfide nanocrystals through coordination interaction, and simultaneously inhibits the further growth of bismuth sulfide nanocrystals, rendering the bismuth sulfide nanocrystals like rivets inlaying onto the polypeptide firmly, which can not only strengthen the architectural stability of ferritin to prevent drug burst leakage during systemic circulation, but also act as excellent computed tomography contrast agents and nanoradiosensitizers for in vivo imaging-guided cancer combinational treatments.
Conclusions: The design concept of inlaying bismuth sulfide nanocrystals onto the polypeptide shell of doxorubicin-encapsulated ferritin significantly inhibits the tumor growth and simultaneously further broadens the application of ferritin in nanomedicine.
Keywords: ferritin, radiotherapy, chemotherapy, polypeptide subunit, bismuth sulfide