“Manganese Extraction” Strategy Enables Tumor-Sensitive Biodegradability and Theranostics of Nanoparticles

Abstract

Biodegradability of inorganic nanoparticles is one of the most critical issues in their further clinical translations. In this work, a novel "metal ion-doping" approach has been developed to endow inorganic mesoporous silica-based nanoparticles with tumor-sensitive biodegradation and theranostic functions, simply by topological transformation of mesoporous silica to metal-doped composite nanoformulations. "Manganese extraction" sensitive to tumor microenvironment was enabled in manganese-doped hollow mesoporous silica nanoparticles (designated as Mn-HMSNs) to fast promote the disintegration and biodegradation of Mn-HMSNs, further accelerating the breakage of Si-O-Si bonds within the framework. The fast biodegradation of Mn-HMSNs sensitive to mild acidic and reducing microenvironment of tumor resulted in much accelerated anticancer drug releasing and enhanced T1-weighted magnetic resonance imaging of tumor. A high tumor-inhibition effect was simultaneously achieved by anticancer drug delivery mediated by PEGylated Mn-HMSNs, and the high biocompatibility of composite nanosystems was systematically demonstrated in vivo. This is the first demonstration of biodegradable inorganic mesoporous nanosystems with specific biodegradation behavior sensitive to tumor microenvironment, which also provides a feasible approach to realize the on-demand biodegradation of inorganic nanomaterials simply by "metal ion-doping" strategy, paving the way to solve the critical low-biodegradation issue of inorganic drug carriers.

Engineering of inorganic nanoparticles as magnetic resonance imaging contrast agents

“…20f). 208 Such a Mn 2+ doping approach enabled accelerated disassembly of Mn–HMSNs in either mildly acidic or reducing microenvironments by breaking the Mn–O bond and subsequently triggering “manganese extraction,” which further accelerated breakage of Si–O–Si bonds in the framework and biodegradation of HMSNs (Fig. 20g and h).…”

Interfacial Assembly of Mesoporous Silica‐Based Optical Heterostructures for Sensing Applications

“…Yu et al developed “metal ion‐doping (MI‐D)” MSM sensor via a simple and versatile approach, which simultaneously realized MSMs with tumor microenvironment‐triggered biodegradation and theranostic functionalities. In that work, transition metal manganese (Mn) was doped into the MSM framework during particle synthesis to alter the inherent chemical properties of MSNs, in particular the biodegradation behavior …”

Recent Progress on Manganese‐Based Nanostructures as Responsive MRI Contrast Agents

“…To date, only pH and redoxs tate have been used as triggerst os witch the power of Mn nanomaterials ON as CAs, and in most cases the effect of pH and redoxp otentialc annot be separated. [29][30][31][32][33] For example, in the case of MnO 2 ,t he mechanism behind its reductionb yH 2 O 2 to Mn 2 + responds to the following hemi-reactions and will be spontaneous at room temperature( DG < 0; DG = ÀnFE 0 )[ Eqs. (1) and (2)]:…”