Sialic acid–targeted drug delivery and imaging system for pH- and glutathione-triggered multiple anticancer drug release and enhanced oxidative stress

The emergence of multiple drug delivery systems can solve the disadvantages of single-drug therapy, such as high dose and easy generation of drug resistance. Here, we designed a sialic acid–targeted dextran-mercaptopurine prodrug linked by carbonyl vinyl sulfide for coordinate ZnO quantum dots to achieve multiple drug delivery (doxorubicin, 5-fluorouracil, 6-mercaptopurine), which can be released under the trigger of pH and glutathione. To enhance the antitumor effect, we used inorganic photosensitizer CdSe quantum dots to achieve photodynamic therapy, which can produce cytotoxic reactive oxygen species (hydroxyl radicals) under light conditions. Notably, we found that glutathione is consumed by the delivery of 6-mercaptopurine. It is able to efficiently amplify intracellular oxidative stress via increasing •OH generation. After chelating 99mTc4+ radioisotopes by diethylenetriamine pentaacetic acid, the drug delivery system could be tracked under in vivo single-photon emission computed tomography imaging. The results showed that the phenylboronic acid targeting substance can specifically recognize sialic acid, so that the drug system has a good accumulation in the tumor site, which can better increase the therapeutic effect. Compared to free doxorubicin, the drug system can reduce the IC50 value of cells 4.4-fold under light conditions and significantly inhibit tumor growth in vivo. These data indicate that the sialic acid–targeted nanomedicine system has achieved ideal antitumor effects and apparent photodynamic therapy effects and has broad application prospects.

Multicompartmental Mesoporous Silica/Polymer Nanostructured Hybrids: Design Capabilities by Integrating Linear and Star-Shaped Block Copolymers

Poly(2-vinyl pyridine)-b-poly(ethylene oxide) (P2VP-b-PEO) linear diblock copolymer and polystyrene–poly(ethylene oxide) (PS10PEO10) heteroarm star copolymer were used as building elements to prepare organic–inorganic hybrids. By using the layer-by-layer (LbL) methodology, these elements were integrated on mesoporous silica through non-covalent interactions, namely, ionic and H-bonding. For the latter, tannic acid (TA) was used as an intermediate layer. The deposition of the various layers was monitored by thermogravimetric analysis (TGA), electrophoretic measurements, and confocal microscopy. The final silica hybrid, bearing alternating P2VP-b-PEO and PS10PEO10 star layers was capable of carrying one hydrophilic and two hydrophobic chemical species in distinct compartments. These multicompartmental organic–inorganic hybrids could be used as nanostructured carriers for pH-responsive multiple drug delivery and potential theranostic applications.

HYBRID INTELLIGENT CONTROLLERS FOR A MULTIPLE DRUG DELIVERY SYSTEM IN ACUTE HEART FAILURE

Regulating the dynamic responses to multiple therapeutic agents in cases of heart failure is difficult owing to time-variant changes in drug sensitivity and interaction. To address this problem, a multiple controller based on adaptive neural network (NN) predictive control has been developed for unexpected drug responses related to cardiac output and arterial pressure. However, the control speed may be slower than that in traditional controllers because of the real-time learning process for the NN. Moreover, a proportional-integral-derivative (PID) controller alone cannot automatically update the PID parameters during drug administration. This study, therefore, aimed to make hybrid intelligent (fuzzy or NN-based PID) controllers and to evaluate the control performance during multiple drug therapy in unexpected physiological responses of heart failure. The hybrid intelligent controllers were compared with the previous PID or NN controller, and they realized robust and quick control regardless of unexpected responses and acute disruptions.