Size-Controlled Functionalized Mesoporous Silica Nanoparticles for Tunable Drug Release and Enhanced Anti-Tumoral Activity

Abstract

Mesoporous silica nanoparticles (MSNs) are considered as one of the most promising nanovectors for controlled drug delivery. For the design of ideal drug nanocarriers, several factors have to be taken into account, such as size and surface chemistry. Here, we report how MSNs surface functionalization and particle size critically affect the drug release performances and therapeutic capabilities. We illustrate the size effect of these functionalized MSNs on in vitro, intracellular, and in vivo drug release efficiency, as well as on nanoparticle and drug diffusion into the targeted tissues (tumor). For this, dispersible MSNs with different particle sizes (from 500 down to 45 nm), similar physicochemical properties (e.g., structural and textural properties), and high colloidal stability (even in saline conditions), were synthesized. Their surface was specifically functionalized with a phosphonate-silane according to a novel postgrafting strategy, for better control over loading and release of positively charged drugs. An efficient particle-size-dependent and pH-dependent release of the loaded drug (i.e., doxorubicin) was achieved in physiological conditions with phosphonated-MSNs compared to pure-MSNs. The cellular uptake efficiency is much higher with the smallest phosphonated-nanoparticles (45 nm). Furthermore, doxorubicin is efficiently released from the nanoparticles into the intracellular compartments, and the drug reaches the nucleus in a time- and particle size-dependent manner. Intratumoral diffusion of the developed nanoparticles, as well as the drug release and its diffusion into the tumor matrix, is clearly enhanced with the smallest phosphonated-nanoparticles (45 nm), leading ultimately to a superior cell and tumor growth inhibition.

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

“…Silanol groups present on the surface of MSNs can be functionalized with various ligands, which could be one way of controlling nanoparticle (NP) biodistribution and the design of specific targeted delivery systems (Bouchoucha et al 2016;Li et al 2016). MSNs have been widely studied for their capability to load and release various drugs (Vallet-Reg ı, Balas, and Arcos 2007; Deodhar, Adams, and Trewyn 2017).…”

Mesoporous Silica Nanoparticles for the Treatment of Complex Bone Diseases: Bone Cancer, Bone Infection and Osteoporosis

“…There are various examples of the suitability of using silica-based mesoporous nanomatrices for the delivery of antitumoral [144][145][146][147][148] or imaging agents [137,149,150] to bone cancer cells. Moreover, researchers have taken advantage of the features of the bone tumoral environment to design stimuli-responsive MSNs for the treatment of sarcomas.…”

A Review of Recent Developments of Mesoporous Materials

“…A recent article concerns the use of nano-size particles of mesoporous silica and how the control of functionalization of surfaces of these materials as well as particle size markedly influence the drug release process in their potential application in therapeutics. [8] The size effects of mesoporous nano-size particles of silica are significant in intracellular, in vitro, and in vivo operation of the efficiency of the release of drugs. There are also favorable effects of such nano-sized systems concerning diffusion of drugs into the targeted tumor tissues.…”