Freely Tailorable Yolk-Shell Encapsulation: Versatile Applications in Ultralow-k Dielectric,Drug Delivery Systems,and Catalysts

Herein, a facile, controllable, and versatile method is reported to prepare monodisperse yolk-shell and yolk-multishell silica nanoparticles (NPs) with mesoporous shells by a novel selective etching strategy. The mechanism of selective etching based on fluoride-silica chemistry is investigated in detail and thus provides a fundamentally novel principle for the fabrication of yolk-shell NPs. Specifically, this unprecedented and versatile synthesis strategy can be used to encapsulate essentially any silica-based, carbon-based, metal, metal oxide, or other possible NPs. Noteworthy is that most of the yolk-shell mesoporous silica (mSiO₂) NPs are prepared for the first time. To demonstrate the major structural and compositional advantages of the designed yolk-shell NPs, their applications in the fields of ultralow-dielectric constant (k) materials, drug delivery systems, and catalysts were explored. In detail, the lowest k value of the prepared yolk-shellordered mesoporous silica@mSiO₂/fluorinated polybenzoxazole composite films is 2.02; The obtained yolk-shell mSiO₂/C@mSiO₂/C NPs possess high hydrophilicity and pH-responsive sensitivity; The conversion of the catalytic reaction of the designed magnetic yolk-shell hollow Fe₃O₄@SiO₂/Au@mSiO₂ NPs at 20 min is 97% with a high conversion rate (92%) and recyclability even after 10 reuses. This innovative work lays a solid foundation for freely tailorable yolk-shell encapsulation and will greatly stimulate more efforts devoted to relevant research and development.     

Data-enabled learning and control algorithms for intelligent glucose management: The state of the art

External insulin administration is an effective way for patients with diabetes mellitus to regulate their blood glucose. Multiple daily injections (MDIs), sensor-augmented pump (SAP) and artificial pancreas (AP) are widely adopted approaches in insulin therapy. With the increasing popularity of continuous glucose monitoring (CGM) sensors, a large number of data-enabled learning and control algorithms have been developed for MDI, SAP and AP. In this paper, we perform a systemic review concerning the state-of-the-art methodologies that are developed for MDI, SAP and AP with feedback from CGM data or other available data, from a systems and control perspective. The review characterizes the traditional learning and control methods developed for the MDI, SAP and AP, including run-to-run control, proportional–integral–derivative control, fuzzy logic control and model predictive control, as well as the discussions on the roles of machine learning technologies in MDI, SAP and AP. Finally, potential future directions on the algorithm architecture design, a unified control framework for MDI, SAP and AP algorithm design and practical usage of the MDI, SAP and AP are discussed.     

Coating nanodiamonds with biocompatible shells for applications in biology and medicine

Use of nanodiamonds (NDs) as nontoxic nanoparticles for biological imaging, sensing, and drug delivery is expanding rapidly. The interest in NDs is triggered by their unique combination of optical properties. ND can accommodate nitrogen-vacancy color centers which provide stable fluorescence without photobleaching or photoblinking and their electronic structure is very sensitive to magnetic and electric fields. The limited options to control ND properties during synthesis or by direct surface functionalization leave room to be improved upon by employing surface coatings engineered precisely for a particular application. The major disadvantages of unmodified NDs are their limited colloidal stability and tendency to non-specifically adsorb biomolecules. This review aims to summarize recent advances in coating NDs (namely with silica and polymer shells), which addresses these disadvantages and enables the use of NDs in biological applications such as targeting of specific cells, drug delivery, and biological imaging.     

Drug‐Loaded Mesoporous Tantalum Oxide Nanoparticles for Enhanced Synergetic Chemoradiotherapy with Reduced Systemic Toxicity

Combining chemotherapy and radiotherapy (chemoradiotherapy) has been widely applied in many clinical practices, showing promises in enhancing therapeutic outcomes. Nontoxic nanocarriers that not only are able to deliver chemotherapeutics into tumors, but could also act as radiosensitizers to enhance radiotherapy would thus be of great interest in the development of chemoradiotherapies. To achieve this aim, herein mesoporous tantalum oxide (mTa₂O₅) nanoparticles with polyethylene glycol (PEG) modification are fabricated. Those mTa₂O₅‐PEG nanoparticles could serve as a drug delivery vehicle to allow efficient loading of chemotherapeutics such as doxorubicin (DOX), whose release appears to be pH responsive. Meanwhile, owing to the interaction of Ta with X‐ray, mTa₂O₅‐PEG nanoparticles could offer an intrinsic radiosensitization effect to increase X‐ray‐induced DNA damages during radiotherapy. As a result, DOX‐loaded mTa₂O₅‐PEG (mTa₂O₅‐PEG/DOX) nanoparticles can offer a strong synergistic therapeutic effect during the combined chemoradiotherapy. Furthermore, in chemoradiotherapy, such mTa₂O₅‐PEG/DOX shows remarkably reduced side effects compared to free DOX, which at the same dose appears to be lethal to animals. This work thus presents a new type of mesoporous nanocarrier particularly useful for the delivery of safe and effective chemoradiotherapy.     

Redox and pH Dual Responsive Polymer Based Nanoparticles for In Vivo Drug Delivery

Responsive nanomaterials have emerged as promising candidates as drug delivery vehicles in order to address biomedical diseases such as cancer. In this work, polymer‐based responsive nanoparticles prepared by a supramolecular approach are loaded with doxorubicin (DOX) for the cancer therapy. The nanoparticles contain disulfide bonds within the polymer network, allowing the release of the DOX payload in a reducing environment within the endoplasm of cancer cells. In addition, the loaded drug can also be released under acidic environment. In vitro anticancer studies using redox and pH dual responsive nanoparticles show excellent performance in inducing cell death and apoptosis. Zebrafish larvae treated with DOX‐loaded nanoparticles exhibit an improved viability as compared with the cases treated with free DOX by the end of a 3 d treatment. Confocal imaging is utilized to provide the daily assessment of tumor size on zebrafish larva models treated with DOX‐loaded nanoparticles, presenting sustainable reduction of tumor. This work demonstrates the development of functional nanoparticles with dual responsive properties for both in vitro and in vivo drug delivery in the cancer therapy.     

Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

Currently,sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients.Unfortunately,its side effects,particularly its overall toxicity,limit the therapeutic response that can be achieved.Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field,thus improving intratumoral accumulation and reducing adverse effects.Here,nanoformulations based on polyethylene glycol modified phospholipid micelles,loaded with both SPIONs and sorafenib,were successfully prepared and thoroughly investigated by complementary techniques.This nanovector system provided effective drug delivery,had an average hydrodynamic diameter of about 125 nm,had good stability in aqueous medium,and allowed controlled drug loading.Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle.An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver.Human hepatocellular carcinoma (HepG2) cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib.These experiments demonstrated that this delivery platform is able to enhance sorafenib's antitumor effectiveness by magnetic targeting.The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites,where selective release of sorafenib can improve its efficacy and safety profile.     

Online hot selling period and its impact on e-retailer’s pricing strategies

The express delivery industry is often overloaded in some hot online selling seasons, which causes consumers’ dissatisfaction. Under such a circumstance, the e-retailer can utilise two opposite strategies, i.e. to set-up either a low price with a pre-announced markdown pricing (PMDP) strategy, or a high price with a pre-announced markup pricing (PMUP) strategy for the hot selling period. As both the prices and the express service quality are different between the regular period and the hot selling period, consumers can strategically choose their purchase time, which will in turn influences the e-retailer’s pricing strategy. To investigate under what condition one pricing strategy will dominate the other, we propose a two period pricing model in which the selling season are divided into regular and hot selling period, and all consumers are assumed to be strategic. The e-retailer determines the prices over the two kinds of periods to maximise its profit. The comparison shows that a PMUP (resp. PMDP) strategy is preferred when the overloading degree in the hot selling period is slight (resp. heavy). Furthermore, we extend our model by incorporating the competition of traditional retailers.     

The influence of bile salts on the distribution of simvastatin in the octanol/buffer system

Abstract

Introduction: Distribution coefficient (D) is useful parameter for evaluating drugs permeability properties across biological membranes, which are of importance for drugs bioavailability. Given that bile acids are intensively studied as drug permeation-modifying and -solubilizing agents, the aim of this study was to estimate the influence of sodium salts of cholic (CA), deoxycholic (DCA) and 12-monoketocholic acids (MKC) on distribution coefficient of simvastatin (SV) (lactone [SVL] and acid form [SVA]) which is a highly lipophilic compound with extremely low water solubility and bioavailability.

Methods: LogD values of SVA and SVL with or without bile salts were measured by liquid–liquid extraction in n-octanol/buffer systems at pH 5 and 7.4. SV concentrations in aqueous phase were determined by HPLC-DAD. Chem3D Ultra program was applied for computation of physico-chemical properties of analyzed compounds and their complexes.

Results: Statistically significant decrease in both SVA and SVL logD was observed for all three studied bile salts at both selected pH. MKC exerted the most pronounced effect in the case of SVA while there were no statistically significant differences between observed bile salts for SVL. The calculated physico-chemical properties of analyzed compounds and their complexes supported experimental results.

Conclusions: Our data indicate that the addition of bile salts into the n-octanol/buffer system decreases the values of SV distribution coefficient at both studied pH values. This may be the result of the formation of hydrophilic complexes increasing the solubility of SV that could consequently impact the pharmacokinetic parameters of SV and the final drug response in patients.