Hybrid Mesoporous Silica Nanoparticles with pH‐Operated and Complementary H‐Bonding Caps as an Autonomous Drug‐Delivery System

Abstract

Mesoporous silica nanoparticles (MSNPs) are functionalized with molecular-recognition sites by anchoring a triazine or uracil fragment on the surface. After loading these MSNPs with dyes (propidium iodide or rhodamine B) or with a drug (camptothecin, CPT) they are capped by the complementary fragments, uracil and adenine, respectively, linked to the bulky cyclodextrin ring. These MSNPs are pH-sensitive and indeed, the dye release was observed at acidic pH by continuously monitored fluorescence spectroscopy studies. On the other hand, no dye leakage occurred at neutral pH, hence meeting the non-premature requirement to minimize side effects. In vitro studies were performed and confocal microscopy images demonstrate the internalization of the MSNPs and also dye release in the cells. To investigate the drug-delivery performance, the cytotoxicity of CPT-loaded nanoparticles was tested and cell death was observed. A remarkably lower amount of loaded CPT in the MSNPs (more than 40 times less) proved to be as efficient as free CPT. These results not only demonstrate the drug release after pore opening under lysosomal pH, but they also show the potential use of these MSNPs to significantly decrease the amount of the administered drug.

Protein-gold clusters-capped mesoporous silica nanoparticles for high drug loading, autonomous gemcitabine/doxorubicin co-delivery, and in-vivo tumor imaging

“…[26][27][28][29][30][31][32][33][34] MSN are biocompatible nanomaterials [35,36] and possess disctinctive characteristics such as their tunable porosity and particle size, versatile inner and outer surface chemistry, and capacity to transport and deliver various cargos make these scaffolds ideal drug delivery systems. [37,38] Both molecular and supramolecular nanomachines have been designed with MSN to precisely control the release of guest molecules from their nanopores upon various stimuli including pH, [39,40] one- [41,42] and two-photon irradiation, [43][44][45] enzymes [46,47] and redox processes. [48] Capping the pores of MSN was also carried out with inorganic particles, [49,50] dendrimers, [51] and covalently-attached proteins.…”

Development of mesoporous silica-based nanoparticles with controlled release capability for cancer therapy

“…Theron et al [63] designed a cap that employed stable multi-H-bonded and base-pairing systems. After the loading with drug molecules, the nanoparticles were capped through hydrogen bonds with complementary nucleic acids, prepared with covalently coupling a uracil or an adenine unit to the bulky β-cyclodextrin.…”

“…These H-bonds can be cleaved under mild acidic conditions. Cell experiments with human cancer cells showed a quick release of anticancer drugs inside cancer cells and a decrease in cell viability similar to that of the drug alone, suggesting effective pH-responsive release of loaded anticancer drugs [63]. Nanomachines activated by a pH change can also be combined with polymer coatings on mesoporous silica nanoparticles to produce a new generation of nanoparticles that can increase the cellular uptake, avoid the reticuloendothelial uptake, enhance tumor accumulation of nanoparticles, and respond to acidic microenvironment in the tumor.…”

pH-operated hybrid silica nanoparticles with multiple H-bond stoppers for colon cancer therapy

“…2 In addition, surgery is oen followed by adjuvant chemotherapy (oxaliplatin or 5-FU) to eradicate eventual micro-metastases. 5 In one case, a nucleobase (uracyl moieties) bonded to b-cyclodextrin was used as snap top which were linked via a single molecular recognition pattern of three Hbonds to a triazine stalk graed on MCM-41 type mesoporous silica nanoparticles. Even if these strategies are signicantly efficient to treat tumors and metastases, they are oen followed by vital organ function decline, particularly for older patients.…”

“…5 Cetyltrimethyl-ammonium bromide (CTAB) was used as the surfactant to construct the hexagonal compact porosity with a N 2 adsorption-desorption analysis Brunauer, Emmett and Teller (BET) surface area of 1086 m 2 g À1 . 5 Cetyltrimethyl-ammonium bromide (CTAB) was used as the surfactant to construct the hexagonal compact porosity with a N 2 adsorption-desorption analysis Brunauer, Emmett and Teller (BET) surface area of 1086 m 2 g À1 .…”