Hybrid Enzyme‐Polymeric Capsules/Mesoporous Silica Nanodevice for In Situ Cytotoxic Agent Generation

Abstract

A novel nanocarrier based on functionalized mesoporous silica nanoparticles able to transport a non-toxic pro-drug and the enzyme responsible for its activation has been presented. This nanodevice is able to generate in situ cytotoxic species once accumulated in the tumoral cell.Enzymes are sensitive macromolecules which can suffer denaturalization in biological media due to the presence of proteases or other aggressive agents. Moreover, the direct attachment of enzymes to the silica surface could reduce their activity by conformational changes or active site blockage. For these reasons, in order to create a robust system able to work in living organisms, the enzymes were previously coated with a protective polymeric shell which allows the attachment on the silica surface preserving their activity. The efficacy of this hybrid nanodevice for antitumoral purposes has been tested against several human tumoral cells as neuroblastoma and leukemia showing significant efficacy. It converts this device in a promising candidate for further in vivo studies for oncology therapy.

Synthesis of Polydopamine‐Like Nanocapsules via Removal of a Sacrificial Mesoporous Silica Template with Water

“…In a typical experiment, dopamine was dissolved in isopropanol and polymerized with an aqueous solution of ammonia (25 % in water) at 45 °C. Simultaneously, MSNs were prepared according to a modified Stöber method (see Experimental Section and Supporting Information, Figure S1), were added resulting in the formation of well‐defined, uniform and reproducible coatings after 12 h. Moreover, in order to examine the role of the particle size in the coating process, two different batches of MSNs were prepared. From now on MSN 140 or MSN 350 refer to MSN nanoparticles used in this work with mean sizes of 140 or 350 nm, respectively.…”

Decidua-derived mesenchymal stem cells as carriers of mesoporous silica nanoparticles. In vitro and in vivo evaluation on mammary tumors

“…NPs were synthesized by modifying previous methods. [23] Briefly, APTES-dyes were synthesized by labeling 3-aminopropyl triethoxysilane (APTES) with active groups of dyes. For example, APTES (2.2 µL) was labeled with 1 mg of fluorescein isothiocyanate (FITC) in 100 µL of ethanol solution.…”

Hybrid Collagenase Nanocapsules for Enhanced Nanocarrier Penetration in Tumoral Tissues

“…12 Lu et al 13,14 have reported an interesting strategy which consists in the enzyme encapsulation into polymeric nanocapsules in order to improve their resistance and to preserve their activity during longer times. Our research group has described the attachment of enzyme nanocapsules onto the nanoparticle surface for the development of devices able to generate in situ cytotoxic compounds 15 and also for the propulsion of nano-and micromotors. 16 Herein, we describe the design and attachment of hybrid collagenase-polymeric nanocapsules on the surface of mesoporous silica nanoparticles in order to improve their penetration within 3D collagen matrices with tumoral cells embedded within the network, which mimic tumoral tissues.…”