Enhancing Doxorubicin Delivery in Solid Tumor by Superhydrophobic Amorphous Calcium Carbonate-Doxorubicin Silica Nanoparticles with Focused Ultrasound.

The current approach of delivering chemotherapy via pH-sensitive amorphous calcium carbonate-doxorubicin silica nanoparticles (ADS NPs) faces the challenge of insufficient drug dose due to drug instability within the bloodstream and poor tumor penetration. To overcome these long-standing obstacles, we proposed a superhydrophobic coating on the surface of the ADS NPs that could be easily modified via fluorination (ADSF NPs). The surface of fluorinated ADS NPs was further modified with a phospholipid layer to reduce aggregation and improve biocompatibility (ADSFL NPs). The contact angle and mean size of ADSFL NPs were 30.2 ± 4.4° and 353.1 ± 54.2 nm, respectively. The superhydrophobic layer generated interfacial nanobubbles on the outer shell of the NPs that reduced water-induced leakage of doxorubicin (DOX) sevenfold compared with the uncoated group and induced a cavitation effect upon ultrasound (US) sonication. Moreover, release of DOX from the ADSFL NPs could be triggered by US, and this release was further improved 1.6-fold in acidic aqueous conditions, indicating that the ADSFL NPs retained pH responsiveness. Enhanced sonography contrast and histological examination demonstrated that US could trigger cavitation activities from ADSFL NPs in vivo to induce vessel disruption and enhance the fluorescence intensity of DOX within the tumor region threefold under US imaging guidance compared with the ADSFL NPs-only group.

State-of-the-art of ultrasound-triggered drug delivery from ultrasound-responsive drug carriers.

INTRODUCTION: Delivering sufficient therapeutics at the target site without off-target effects is a major goal of drug delivery technology innovation. Among the established methods, ultrasound (US) with US-responsible carriers holds great promise and demonstrates on-demand delivery of a variety of functional substances with spatial precision of several millimeters in deep-seated tissues in animal models and humans. These properties have motivated several explorations of US with US responsible-responsible carriers as a modality for neuromodulation and the treatment of various diseases, such as stroke and cancer. AREAS COVERED: We briefly discuss three specific mechanisms that enhance in vivo drug delivery via US with US-responsible carriers: 1) permeabilizing cellular membrane, 2) increasing the permeability of vessels, and 3) promoting cellular endocytotic uptake. We then reviewed the state-of-the-art materials for US-triggered drug delivery, including conventional US contrast agents, and nanocarrier formulations, such as inorganic nanoparticles and gas vesicles. EXPERT OPINION: In this article, we summarized recent progress for each of US-responsible drug carrier, focusing on the routes of enhancing delivery and applications. The mechanisms of interaction between US-responsible carriers and US waves, such as cavitation, streaming, hyperthermia, and ROS, as well as how those interactions can improve drug release and cell/tissue uptake.

Mesoporous TiO2 Microparticles with Tailored Surfaces, Pores, Walls, and Particle Dimensions Using Persistent Micelle Templates.

Mesoporous microparticles are an attractive platform to deploy high-surface-area nanomaterials in a convenient particulate form that is broadly compatible with diverse device manufacturing methods. The applications for mesoporous microparticles are numerous, spanning the gamut from drug delivery to catalysis and energy storage. For most applications, the performance of the resulting materials depends upon the architectural dimensions including the mesopore size, wall thickness, and microparticle size, yet a synthetic method to control all these parameters has remained elusive. Furthermore, some mesoporous microparticle reports noted a surface skin layer which has not been tuned before despite the important effect of such a skin layer upon transport/encapsulation. In the present study, material precursors and block polymer micelles are combined to yield mesoporous materials in a microparticle format due to phase separation from a homopolymer matrix. The skin layer thickness was kinetically controlled where a layer integration via diffusion (LID) model explains its production and dissipation. Furthermore, the independent tuning of pore size and wall thickness for mesoporous microparticles is shown for the first time using persistent micelle templates (PMT). Last, the kinetic effects of numerous processing parameters upon the microparticle size are shown.

Material Discovery and High Throughput Exploration of Ru Based Catalysts for Low Temperature Ammonia Decomposition.

High throughput experimentation has the capability to generate massive, multidimensional datasets, allowing for the discovery of novel catalytic materials. Here, we show the synthesis and catalytic screening of over 100 unique Ru-Metal-K based bimetallic catalysts for low temperature ammonia decomposition, with a Ru loading between 1-3 wt% Ru and a fixed K loading of 12 wt% K, supported on γ-Al2O3. Bimetallic catalysts containing Sc, Sr, Hf, Y, Mg, Zr, Ta, or Ca in addition to Ru were found to have excellent ammonia decomposition activity when compared to state-of-the-art catalysts in literature. Furthermore, the Ru content could be reduced to 1 wt% Ru, a factor of four decrease, with the addition of Sr, Y, Zr, or Hf, where these secondary metals have not been previously explored for ammonia decomposition. The bimetallic interactions between Ru and the secondary metal, specifically RuSrK and RuFeK, were investigated in detail to elucidate the reaction kinetics and surface properties of both high and low performing catalysts. The RuSrK catalyst had a turnover frequency of 1.78 s-1, while RuFeK had a turnover frequency of only 0.28 s-1 under identical operating conditions. Based on their apparent activation energies and number of surface sites, the RuSrK had a factor of two lower activation energy than the RuFeK, while also possessing an equivalent number of surface sites, which suggests that the Sr promotes ammonia decomposition in the presence of Ru by modifying the active sites of Ru.

Superhydrophobic drug-loaded mesoporous silica nanoparticles capped with ß-cyclodextrin for ultrasound image-guided combined antivascular and chemo-sonodynamic therapy.

Interfacial nanobubbles (INBs) on a superhydrophobic surface has been proposed as a solid cavitation agent for enhancing inertial cavitation dose and ultrasound contrast imaging, but the dispersibility of superhydrophobic particles limits the biomedical application. For this study, we designed superhydrophobic mesoporous silica nanoparticles loaded with the anti-tumor drug Doxorubicin (FMSNs-Dox) for tumor therapy. The ß-cyclodextrin was used to cap the superhydrophobic surface of FMSNs-Dox to reduce aggregation without inhibiting the accumulation of INBs. The mean size and a contact angle of FMSNs-Dox was 217 ± 58 nm and 129 ± 3°, respectively. The INBs cavitation on the surface of FMSNs-Dox during ultrasound sonication disrupted tumor vessels to allow a large amount of drug penetrating and trapping within tumors. The reduced tumor perfusion, histological reactive oxygen species staining, and tumor inhibition demonstrated that FMSNs-Dox sonication combined anti-vascular, sonodynamic and chemical therapies in a simple platform. Moreover, the repeatability of INB cavitation by single-injection FMSNs-Dox with multiple ultrasound sonication provided intratumoral ultrasound contrast-enhanced imaging from day 1-9 (enhancement of 3.84 ± 0.47 dB). Therefore, the characteristics of FMSNs-Dox with slow biodegradation and acoustic-sensitivity presented intratumoral day-scaled lifetime to provide a probability of repeated combination therapy by single-injection.

Quantitative analysis of estrogens and estrogen metabolites in endogenous MCF-7 breast cancer cells by liquid chromatography-tandem mass spectrometry.

To study the roles of estrogens and estrogen metabolites (EMs) in breast carcinogenesis, we reported a quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) method utilizing selective reaction mode (SRM) to analyze estrogens and EMs in the extracellular and intracellular compartments of endogenous MCF-7 breast cancer cells through simple ethyl acetate (EA) extraction and dansyl chloride derivatization. Under a 35-min LC gradient elution on a reversed phase C18 column, the method was shown to simultaneously quantify 12 estrogens and EMs: estrone (E1) and its 2-, 4-, 16α-hydroxy derivatives (2-OHE1, 4-OHE1, 16α-OHE1), and 2-, 4-methoxy derivatives (2-MeOE1, 4-MeOE1); 17ß-estradiol (E2) and its 2-, 4-hydroxy derivative (2-OHE2, 4-OHE2) and 2- and 4-methoxy derivatives (2-MeOE2 and 4-MeOE2); and estriol (E3), using ethinylestradiol (EE2) as the internal standard (IS). Using a calibration curve-standard addition hybrid method, we were able to determine the amount of estrogens and EMs in not only the treated cells but also the non-treated cells. The limits of quantification (LOQs) were determined to range from 0.05-80 pg on column with an inter-batch accuracy around 72-123% and precision around 1-10%. Results indicated that trace amounts (<0.9 fg/cell) of E1 and E2 were present in both the extra- and intra-cellular compartments under non-treated condition but DMSO could induce E1 and E2 as well as trace amounts (<2.25 fg/cell) of EMs in the cell. E2 treatment substantially increased not only E1 and E2 in the intra-cellular (60 fg/cell) and extra-cellular (3000 fg/cell) compartment but also substantially induced EMs primarily in the extracellular compartment (0.6-25 fg/cell). These data implied that EMs could be quickly generated and distributed to the extracellular compartment by E2 within 24h of treatment and DMSO solvent could potentially induce slight estrogen effects.