Design of hybrid protein-coated magnetic core-mesoporous silica shell nanocomposites for MRI and drug release assessed in a 3D tumor cell model

Abstract

In this work, we describe the design and the use of a novel theranostic hybrid nanocomposite made of an iron oxide core and a mesoporous silica shell (IO@MS) of ca. 30 nm coated by human serum albumin (HSA) layer for magnetic resonance imaging (MRI) and drug delivery applications. The porosity of IO@MS nanoparticles was loaded with an antitumoral drug, Doxorubicin (Dox) reaching a high drug loading capacity (DLC) of 34w%. To entrap the drug, a tight HSA coating held via isobutyramide (IBAM) binders was deposited. We show that this protein nanoassembly entraps the drugs efficiently and behaves as an innovative enzymesensitive gatekeeper that is degraded upon protease action. Finally we assess the Dox release in a 3D cell model via confocal imaging and its cytotoxicity is shown by growth inhibition studies on liver cancer cell spheroids.

Mesoporous Silica Nanoparticles in Bioimaging

“…To obtain greater control over DOX release, a responsive gatekeeper can be incorporated [ 87 ]. A recent example by Ménard et al coated core/shell SPION/MSN particles with human serum albumin (HSA) through iso butyramide linkers for environmentally responsive drug delivery [ 99 ]. In the presence of protease enzymes, this HSA coating is degraded allowing for the enzyme-sensitive release of DOX to the surrounding medium.…”

Emerging and Innovative Theranostic Approaches for Mesoporous Silica Nanoparticles in Hepatocellular Carcinoma: Current Status and Advances

“…In other reports, it has been well established that there is over expression of some enzymes in HCC, such as protease (Menard et al, 2019), glycosidase (Hakeem et al, 2016), and esterase (Xia et al, 2017). Once the enzyme is found at higher level in the tumor site, the MSNs can be programmed to targeting release of agents via enzymatic conversion of the carrier.…”

Design and applications of protein delivery systems in nanomedicine and tissue engineering

“…The last common stimulus inducing the degradation of delivery systems is the presence of proteases [30,44,118,120,121]. This sensibility to protease can come from the nature of the material, like the sensitivity of COL toward collagenase, or from specific functionality added to the material.…”