Coordination‐Accelerated “Iron Extraction” Enables Fast Biodegradation of Mesoporous Silica‐Based Hollow Nanoparticles

Biodegradation behavior of inorganic silica-based nanoplatforms is of critical importance in their clinical translations, but still remains a great challenge in achieving this goal by composition regulation of biocompatible silica framework. In the present work, a chemical coordination-accelerated biodegradation strategy to endow hollow mesoporous silica nanoparticles (HMSNs) with unique coordination-responsive biodegradability, on-demand coordination-responsive drug releasing behavior, and significantly enhanced chemotherapeutic efficacy by directly doping iron (Fe) ions into the framework of mesoporous silica is reported. A simple but versatile dissolution-regrowth strategy has been developed to enable the framework Fe doping via chemical bonding. The deferiprone-mediated biodegradation of Fe-doped HMSNs (Fe-HMSNs) has been comprehensively evaluated both in simulated body fluid and intracellular level, which have exhibited a specific coordination-accelerated biodegradation behavior. In addition to high biocompatibility of Fe-HMSNs, the anticancer drug doxorubicin (DOX)-loaded Fe-HMSNs show enhanced tumor-suppressing effect on 4T1 mammary cancer xenograft. This work paves a new way for tuning the biodegradation performance of mesoporous silica-based nanoplatforms simply by biocompatible Fe-ion doping into silica framework based on the specific coordination property between introduced metal Fe ions with Fe-coordination proteins.