Simultaneous Single-Particle Tracking and Dynamic pH Sensing Reveal Lysosome-Targetable Mesoporous Silica Nanoparticle Pathways.

Nanoparticle (NP)-based targeted drug delivery is intended to transport therapeutically active molecules to specific cells and particular intracellular compartments. However, there is limited knowledge regarding the complete route of NPs in this targeting scenario. In this study, simultaneously performing motion and dynamic pH sensing using single-particle tracking (SPT) leads to an alternative method of gaining insights into the mesoporous silica nanoparticle's (MSN) journey in targeting lysosome. Two different pH-sensitive dyes and a reference dye are incorporated into mesoporous silica nanoparticles (MSNs) via co-condensation to broaden the measurable pH range (pH 4-7.5) of the nanoprobe. The phosphonate, amine, and lysosomal sorting peptides (YQRLGC) are conjugated onto the MSN's surface to study intracellular nano-biointeractions of two oppositely charged and lysosome-targetable MSNs. The brightness and stability of these MSNs allow their movement and dynamic pH evolution during their journey to be simultaneously monitored in real time. Importantly, a multidimensional analysis of MSN's movement and local pH has revealed new model intracellular dynamic states and distributions of MSNs, previously inaccessible when using single parameters alone. A key result is that YQRLGC-conjugated MSNs took an alternative route to target lysosomes apart from the traditional one, which sped up to 4 h and enhanced their targeting efficiency (up to 32%). The findings enrich our understanding of the intracellular journey of MSNs. This study offers complementary information on correlating the surface design with the full pathway of nanoparticles to achieve targeted delivery of therapeutic payload.

Phototherapeutic spectrum expansion through synergistic effect of mesoporous silica trio-nanohybrids against antibiotic-resistant gram-negative bacterium.

The extensive impact of antibiotic resistance has led to the exploration of new anti-bacterial modalities. We designed copper impregnated mesoporous silica nanoparticles (Cu-MSN) with immobilizing silver nanoparticles (SNPs) to apply photodynamic inactivation (PDI) of antibiotic-resistant E. coli. SNPs were decorated over the Cu-MSN surfaces by coordination of silver ions on diamine-functionalized Cu-MSN and further reduced to silver nanoparticles with formalin. We demonstrate that silver is capable of sensitizing the gram-negative bacteria E. coli to a gram-positive specific phototherapeutic agent in vitro; thereby expanding curcumin's phototherapeutic spectrum. The mesoporous structure of Cu-MSN remains intact after the exterior decoration with silver nanoparticles and subsequent curcumin loading through an enhanced effect from copper metal-curcumin affinity interaction. The synthesis, as well as successful assembly of the functional nanomaterials, was confirmed by various physical characterization techniques. Curcumin is capable of producing high amounts of reactive oxygen species (ROS) under light irradiation, which can further improve the silver ion release kinetics for antibacterial activity. In addition, the positive charged modified surfaces of Cu-MSN facilitate antimicrobial response through electrostatic attractions towards negatively charged bacterial cell membranes. The antibacterial action of the synthesized nanocomposites can be activated through a synergistic mechanism of energy transfer of the absorbed light from SNP to curcumin.

Development of in vitro tooth staining model and usage of catalysts to elevate the effectiveness of tooth bleaching.

OBJECTIVES: Whole blood or tea was frequently used to stain the teeth for measuring the effectiveness of different bleaching materials. However, the components of blood or tea cannot be quantitatively determined and variability might exist among different brands of tea. The purpose of this study was to develop a reproducible in vitro tooth-staining model to simulate the intrinsic discoloration of teeth and evaluate the ability of two catalysts to enhance the bleaching activity of H(2)O(2). METHODS: Rhodamine B, Orange II, Fe(III) phthalocyanine, and tea were used to stain the tooth specimens for 4-72 h and subsequently bleached by H(2)O(2) for 4-72 h. The process was photographed using a digital stereoscopic microscope and a digital camera. The image was transformed to get L*, a*, b* values of CIE Lab system with image processing software. The catalytic ability of light irradiation plus addition of Fe/Sodium-Y or Mn/Sodium-Y for specimens stained by Orange II was evaluated in test tubes and in extracted tooth model. RESULTS: The color of specimens stained by Rhodamine B could not be sufficiently recovered after bleaching by H(2)O(2). In addition, the reaction of Fe(III) phthalocyanine with H(2)O(2) in test tubes was too fast to be monitored. Light activation plus use of Fe/Sodium-Y or Mn/Sodium-Y could significantly accelerate the bleaching efficiency of H(2)O(2). SIGNIFICANCE: Orange II was the most appropriate dye for tooth staining among the dyes used in this study. Addition of Fe/Sodium-Y or Mn/Sodium-Y plus light irradiation could elevate the bleaching efficacy of H(2)O(2) for those specimens stained by Orange II.