Small size mesoporous organosilica nanorods with different aspect ratios: Synthesis and cellular uptake

Abstract

In the work, small size thioether-bridged mesoporous organosilica nanorod (MONRs) are successfully synthesized using cetyltrimethylammonium bromide (CTAB) as structure-directing agent and bis[3-(triethoxysilyl)propyl]tetrasulfide (TETS) and tetraethoxysilane (TEOS) as co-precursors. The MONRs have tunable aspect ratios of 2, 3, and 4 (denoted as MONRs-2, MONRs-3, and MONRs-4), small and controllable lengths (75–310 nm), high surface area (570–870 cm² g⁻¹), uniform mesopores (2.4–2.6 nm), large pore volume (0.34 cm³ g⁻¹), and excellent biocompatibility. The uptake of the MONRs by multidrug resistant human breast cancer MDR-MCF-7 cells is related to their aspect ratios. The MONRs-3 shows a faster and higher cellular internalization compared to the MONRs-4 and MONRs-2, respectively. Thanks to the high cellular uptake, doxorubicin (DOX) loaded MONRs-3 show obviously improved chemotherapeutic effect on MDR-MCF-7 cancer cells. It is expected that the MONRs provide a useful platform for drug delivery and therapeutics.

Introduction

In recent years, mesoporous organosilica (MONs) have attracted more and more attention because of their molecularly incorporated organic groups, ordered mesostructures, large surface area, high pore volume, tunable pore size, excellent biocompatibility, and biodegradable properties [1], [2], [3], [4]. MONs with different morphologies including particles [5], hollow [4], yolk-shell [2], [6], [7], films [8], [9], monoliths, and rods [10], [11] have been prepared for various biomedical applications such as drug/gene/protein delivery [12], [13], [14], diagnostic imaging [15], [16], theranostics [17], [18], [19], [20], and functional implants [2], [21], [22]. Because of the unique asymmetric structure, rod like nanoparticles show longer blood circulation half time and higher cellular uptake efficiency [23]. Therefore, synthesis of mesoporous organosilica nanorods is particularly valuable for different biomedical applications such as drug delivery. Doxorubicin (DOX) is a common chemotherapeutic agent for patients with cancer and have excellent efficacy [15]. Recently, mesoporous silica with fibrous morphology with higher surface area was proposed to be effective for DOX delivery [24], [25].

Qiao et al. synthesized ethane-bridged mesoporous organosilica rods using amphiphilic block polymer P123 as a template at low acid concentration with the assistance of inorganic salt [26]. Li et al. prepared mesoporous organosilica rods by co-condensation of bissilylated 1,4-diureylenebenzene precursor and tetraethyl orthosilicate employing P123 as template [10]. However, the prepared mesoporous organosilica rods are micrometer in size, which is difficult to pass the fine blood vessels and the lymphatic endothelium [27], [28]. Therefore, micrometer sized mesoporous organosilica rods are limited in biomedical applications. Recently, Croissant and co-workers prepared ethylene-bis(Propyl)disulfide mesoporous organosilica nanorods with lengths of 130–700 nm using bis(triethoxysilyl)ethylene and bis(3-triethoxysilylpropyl)disulfide as co-precursors [29]. However, the colloidal stability of large particles is relatively poor, which is unfavorable for drug delivery [30], [31], [32]. To the best of our knowledge, MONRs with the length of less than 100 nm have not been reported. Because small nanoparticles possess higher cellular uptake, longer blood circulation, and low uptake by reticuloendothelial system, synthesis of small size MONRs via a facile method is very valuable and desirable [33].

Herein, we successfully synthesized small size thioether-bridged mesoporous organosilica nanorod (MONRs) (length, 75–310 nm) with tunable aspect ratios (AR) of 2, 3, and 4 (denoted as MONRs-2, MONRs-3, and MONRs-4) employing bis[3-(triethoxysilyl)propyl]tetrasulfide (TETS) and tetraethoxysilane (TEOS) as co-precursors. The MONRs have high surface area (570–870 cm² g⁻¹), uniform ordered mesopores (2.4–2.6 nm), and large pore volume (0.34 cm³ g⁻¹). In addition, we reveal that the MONRs have excellent biocompatibility and high cellular uptake efficiency by multidrug resistant human breast cancer MDR-MCF-7 cells. Notably, the cell internalization of the MONRs depends on their aspect ratios and the MONRs-3 show faster and higher cellular uptake than MONRs-4 and MONRs-2. Furthermore, the chemotherapeutic effect of doxorubicin (DOX) loaded MONRs is also varied with their aspect ratios. The DOX-loaded MONRs-3 shows higher chemotherapeutic efficacy against multidrug resistant human breast cancer MDR-MCF-7 cells.