Design, synthesis, and biological evaluation of novel donepezil-tacrine hybrids as multi-functional agents with low neurotoxicity against Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and deficits in cognitive domains. Low choline levels, oxidative stress, and neuroinflammation are the primary mechanisms implicated in AD progression. Simultaneous inhibition of acetylcholinesterase (AChE) and reactive oxygen species (ROS) production by a single molecule may provide a new breath of hope for AD treatment.

Co-delivery of pirfenidone and siRNA in ZIF-based nanoparticles for dual inhibition of hepatic stellate cell activation in liver fibrotic therapy.

Hepatic fibrosis, as a destructive liver disease, occurs due to activated hepatic stellate cells (HSCs) producing excessive extracellular matrix deposition. If left untreated, it could further deteriorate into cirrhosis and hepatoma with high morbidity and mortality. Currently, to break the dilemma of poor targeting efficiency on HSCs and limited effect of monotherapy, it is urgent to explore a precise and efficient treatment against liver fibrosis.

Photothermal antibacterial materials to promote wound healing.

Wound healing is a crucial process that restores the integrity and function of the skin and other tissues after injury. However, external factors, such as infection and inflammation, can impair wound healing and cause severe tissue damage. Therefore, developing new drugs or methods to promote wound healing is of great significance.

Natural saponin and cholesterol assembled nanostructures as the promising delivery method for saponin.

The application of saponins has been restricted by problems such as hemolysis, low bioavailability, and poor solubility. So it is imperative to find a strategy to deliver saponins safely and efficiently. Here, through bottom-up technique, we design and prepare two saponin-cholesterol (Cho) nano-complex: dioscin (Dio, steroid saponin)-Cho nanofibers (NFs) and escin Ia (EIa, triterpene saponin)-Cho nanoparticles (NPs).

Are third-generation active-targeting nanoformulations definitely the best? In vitro and in vivo comparisons of pixantrone-loaded liposomes modified with different sialic acid derivatives.

Treatment with sialic acid-octadecylamine (SA-ODA)-modified pixantrone (Pix) liposomes results in favorable antitumor effects by targeting tumor-associated macrophages (TAMs). To explore the influence of different types of SA decorations on antitumor efficiency, we synthesized a PEGylated SA derivative, SA-PEG-DSPE, and combined it with SA-ODA to construct three representative types of SA-modified liposomes (SA-ODA-modified Pix liposomes, SA-ODA-modified Pix liposomes with different PEG densities, and SA-PEG-DSPE-modified Pix liposomes, named Pix-SACL, Pix-SPL-0.2/0.

Polydopamine-carbon dots functionalized hollow carbon nanoplatform for fluorescence-imaging and photothermal-enhanced thermochemotherapy.

The low power photothermal therapy can reduce the tissue damage caused by laser irradiation, thus the near-infrared (NIR) absorbing vehicles with high photothermal conversion efficiency are demanded in the low power treatment. Herein, the NIR-absorbing agent polydopamine (PDA) and carbon dots (CDs) were gated on the openings of hollow mesoporous carbon (HMC) to construct a photothermal enhanced multi-functional system (HMC-SS-PDA@CDs). Interestingly, the fluorescence emission wavelength of HMC-SS-PDA@CDs was red-shifted by FRET effect between PDA and CDs, which solved the dilemma of fluorescence quenching of carbon-based materials and was more conducive to cell imaging.

Continuous production of celecoxib nanoparticles using a three-dimensional-coaxial-flow microfluidic platform.

Increasing the dissolution rate of water insoluble drugs by decreasing the particle size of the drugs into nano-size is a well-known strategy. However, continuous production of drug nanoparticles with uniform particle size is critical for clinical application of the strategy. Here we report a simple microfluidic mixing method that can achieve continuous production of celecoxib nanoparticles with uniform particle size and high dissolution rate.

Multi-stimuli responsive mesoporous carbon nano-platform gated by human serum albumin for cancer thermo-chemotherapy.

In this work, a multi-stimuli responsive drug delivery system (MCHP) was designed for combinational chemotherapy and photothermal therapy (PTT). Mesoporous carbon nanoparticles (MCN) with a high loading efficiency were used as near-infrared (NIR)-responsive drug carriers. Human serum albumin (HSA) was attached to the pore openings of MCN via disulfide bonds to serve as a gatekeeper due to its biocompatibility and appropriate molecular size.

Chylomicron-pretended nano-bio self-assembling vehicle to promote lymphatic transport and GALTs target of oral drugs.

Lymphatic transport of oral drugs allows extraordinary gains in bioavailability and efficacy through avoidance of first-pass hepatic metabolism and preservation of drugs at lymphatic tissues against lymph-mediated diseases. Chylomicrons can transport dietary lipids absorbed from the intestine to the tissues through lymphatic circulation. Herein, we engineered for the first time a chylomicron-pretended mesoporous silica nanocarrier that utilizes the digestion, re-esterification, and lymphatic transport process of dietary triglyceride to promote lymphatic transport of oral drugs.

Preparation and toxicity evaluation of a novel nattokinase-tauroursodeoxycholate complex.

Nattokinase (NK), which has been identified as a potent fibrinolytic protease, has remarkable potential in treatment of thrombolysis, and even has the ability to ameliorate chronic vein thrombosis. To reduce the hemorrhagic risk from an intravenous injection of NK, nattokinase-tauroursodeoxycholate (NK-TUDCA) complex was prepared at different pH values and with different ratios of NK and TUDCA. When assessing survival time, survival state, tail injury, and the body weight of mice, it was found that the NK-TUDCA complex (NK: 10 kIU/ml; TUDCA: 10 mg/ml; pH 5.

New natural barrigenol-like triterpenoid isolated from the husks of Xanthoceras sorbifolia Bunge.

The Xanthoceras sorbifolia Bunge husks were known for their abundant triterpenoids resource, which contributed to many bioactivities, such as antitumor, antiinflammatory and neuroprotection. The present study has led to the purification of a new triterpenoid saponin, 21β-O-acetyl-xanthohuskiside A (1), together with six known barrigenol derivatives (2-7), whose structures were authenticated on the basis of NMR, HR-MS, IR spectrum and acid hydrolysis experiment. Compound 7 showed more noteworthy cytotoxicity towards three human tumour cell lines (HCT-116, HepG-2 and U87-MG) than other compounds.

Gold nanoparticle-gated mesoporous silica as redox-triggered drug delivery for chemo-photothermal synergistic therapy.

In this paper, a redox-triggered drug delivery system of DOX/MSN-Au was prepared for chemo-photothermal synergistic therapy. The ultra-small gold nanoparticles (NPs) were appended to the openings of mesoporous silica nanoparticles (MSN) by Au-S bonds as the gatekeepers. Meanwhile, the gold NPs could be heated to high temperature by the near infrared (NIR) light irradiation, which is conducive to photothermal therapy.

Fluorescent carbon dot gated hollow mesoporous carbon for chemo-photothermal synergistic therapy.

An efficient and intelligent nano-carrier that combines cell imaging with near infrared (NIR) light and redox dual-responsive drug delivery was successfully prepared. The hollow mesoporous carbon (HMC) nanoparticles with high photothermal conversion ability were developed to increase the drug loading efficiency and realize chemotherapy and photothermal synergetic therapy. The photo-stable and luminescent carbon dots (CDs) were prepared from branched polyethyleneimine (PEI) by hydrothermal reaction.

The antitumor efficacy of docetaxel is enhanced by encapsulation in novel amphiphilic polymer cholesterol-coupled tocopheryl polyethylene glycol 1000 succinate micelles.

Tocopheryl polyethylene glycol 1000 succinate (TPGS) is considered a promising surfactant, but its high critical micelle concentration (CMC) limits its application. Cholesterol is hydrophobic, can act as a tumor-targeting ligand, and has strong binding ability with taxoids. Based on this information, we coupled cholesterol with TPGS to synthesize cholesterol-coupled TPGS (TPGS-CHMC), which had a lower CMC than pure TPGS.

Polysialic acid and pluronic F127 mixed polymeric micelles of docetaxel as new approach for enhanced antitumor efficacy.

In our previous study, polysialic acid-octadecyl dimethyl betaine (PSA-BS18) was synthesized and modified to liposomal EPI. Preliminary experiments revealed that the PSA-BS18 was a potential material for targeting tumor site with superior curative effects. In this study, PSA-BS18 and Pluronic F127 (F127) mixed polymeric micelles encapsulated docetaxel (DTX) (FP/DTX) were prepared by a self-assembly method.

Hyaluronic acid and carbon dots-gated hollow mesoporous silica for redox and enzyme-triggered targeted drug delivery and bioimaging.

In this work, a redox and enzyme dual-stimuli responsive drug delivery system (DDS) with tracking function (HMSN-SS-CD@HA) based on carbon dots capped hollow mesoporous silica nanoparticles (HMSN) has been developed for targeted drug delivery. The positively charged CD nanoparticles prepared by polyethylenimine (PEI) were grafted on the pore openings of HMSN through disulfide bonds and were used as "gatekeepers" to trap the drugs within the hollow cavity. The hyaluronic acid (HA), a natural polysaccharide, was further grafted on the surface of HMSN to realize targeted drug delivery, controlled drug release and improved the stability.

Fluorescent carbon dot-gated multifunctional mesoporous silica nanocarriers for redox/enzyme dual-responsive targeted and controlled drug delivery and real-time bioimaging.

A distinctive and personalized nanocarrier is described here for controlled and targeted antitumor drug delivery and real-time bioimaging by combining a redox/enzyme dual-responsive disulfide-conjugated carbon dot with mesoporous silica nanoparticles (MSN-SS-CD). The carbon dot with controlling and targeting abilities was prepared through a polymerizing reaction by applying citric acid and HA as starting materials (named CD). The as-prepared MSN-SS-CD exhibited not only superior photostability and excellent biocompatibility, but also the ability to target A549 cells with overexpression of CD44 receptors.

Targeted delivery of epirubicin to tumor-associated macrophages by sialic acid-cholesterol conjugate modified liposomes with improved antitumor activity.

With the knowledge that the receptors of sialic acid are overexpressed on the surface of tumor-associated macrophages (TAMs), which play a crucial role in the tumor's progression and metastasis, a sialic acid-cholesterol conjugate (SA-CH) was synthesized and modified on the surface of epirubicin (EPI)-loaded liposomes (EPI-SAL) to improve the delivery of EPI to the TAMs. The liposomes were developed using remote loading technology via a pH gradient. The liposomes were evaluated for particle size, encapsulation efficiency, in vitro release, stability, in vitro cytotoxicity and pharmacokinetics.

A novel nanosuspension of andrographolide: Preparation, characterization and passive liver target evaluation in rats.

Andrographolide (Andro) is an excellent anti-inflammatory bicyclic diterpene γ-lactone. However, the poor solubility limits its application as injection for the treatment of acute inflammation. To meet the clinical needs for emergency, the Andro nanosuspensions injection was first prepared by the wet milling technique.

Hollow mesoporous carbon as a near-infrared absorbing carrier compared with mesoporous carbon nanoparticles for chemo-photothermal therapy.

In this study, hollow mesoporous carbon nanoparticles (HMCN) and mesoporous carbon nanoparticles (MCN) were used as near-infrared region (NIR) nanomaterials and drug nanocarriers were prepared using different methods. A comparison between HMCN and MCN was performed with regard to the NIR-induced photothermal effect and drug loading efficiency. The results of NIR-induced photothermal effect test demonstrated that HMCN-COOH had a better photothermal conversion efficacy than MCN-COOH.

Poly(acrylic acid) conjugated hollow mesoporous carbon as a dual-stimuli triggered drug delivery system for chemo-photothermal synergistic therapy.

In this work, we described the development of the redox and pH dual stimuli-responsive drug delivery system and combination of the chemotherapy and photothermal therapy for cancer treatment. The poly(acrylic acid) (PAA) was conjugated on the outlets of hollow mesoporous carbon (HMC) via disulfide bonds. PAA was used as a capping to block drug within the mesopores of HMC for its lots of favorable advantages, such as good biocompatibility, appropriate molecular weight to block the mesopores of HMC, extension of the blood circulation, and the improvement of the dispersity of the nano-carriers in physiological environment.

Fluorescent carbon dot modified mesoporous silica nanocarriers for redox-responsive controlled drug delivery and bioimaging.

In this paper, a smart nanocarrier (MSNs-SS-CDPAA) is developed for redox-responsive controlled drug delivery and in vivo bioimaging by grafting fluorescent carbon dots to the surface of mesoporous silica nanoparticles (MSNs) via disulfide bonds. The polyanion polymer poly(acrylic acid) (PAA) was used to prepare the carboxyl-abundant carbon dots (CDPAA) by hydrothermal polymerization. The negatively charged CDPAA were anchored to the openings of MSNs containing the disulfide bonds through amidation and were used as gatekeepers for trapping the drugs within the pores.

Redox and pH dual-responsive PEG and chitosan-conjugated hollow mesoporous silica for controlled drug release.

In this paper, a hollow mesoporous silica nanoparticles (HMSN) was used as the drug vehicle to develop the redox and pH dual stimuli-responsive delivery system, in which the chitosan (CS), a biodegradable cationic polymer, was grafted on the surface of HMSN via the cleavable disulfide bonds. CS was chosen as the gatekeeper mainly due to its appropriate molecular weight as well as possessing abundant amino groups which could be protonated in the acidic condition to achieve pH-responsive drug release. In addition, the PEG was further grafted on the surface of CS to increase the stability and biocompatibility under physiological conditions.

Core-matched encapsulation of an oleate prodrug into nanostructured lipid carriers with high drug loading capability to facilitate the oral delivery of docetaxel.

Nanostructured lipid carriers (NLC) have been considered as promising vehicles for oral delivery of taxanes, such as docetaxel (DTX). However, the low drug loading capability (∼5%, w/w) has greatly limited their clinical application. In response to this challenge, a novel lipophilic oleate prodrug of DTX (DTX-OA) was synthesized and efficiently encapsulated in NLC using core-match technology, in which liquid lipid (OA) was used as core matrix to enhance compatibility with DTX-OA.