Three-birds-with-one-stone: An eco-friendly and renewable humic acid-derived material application strategy for macrolide antibiotic detection and multifunctional composite film preparation.

This research proposes a simple and novel strategy for the green detection of antibiotics along with the reduction of microplastic and humic acid (HA) hazards. The entire process is based on a single-step solvent-sieving method to separate HA into insoluble (IHA) and soluble (SHA) components, subsequently recombining and designing the application according to the original characteristics of selected fractions in accordance with the zero-waste principle. IHA was applied as a dispersive solid phase extraction (DSPE) sorbent without chemical modification for the enrichment of trace MACs in complex biological matrices. The recovery of MACs was 74.06-100.84 % in the range of 2.5-1000 µg∙kg-1. Furthermore, SHA could be combined with biodegradable polyvinyl alcohol (PVA) to prepare multifunctional composite films. SHA endows the PVA film with favorable mechanical properties, excellent UV shielding as well as oxidation resistance performance. Compared with pure PVA, the tensile strength, toughness, antioxidant and UV-protection properties were increased to 157.3 Mpa, 258.6 MJ·m-3, 78.6 % and 60 % respectively. This study achieved a green and economically valuable utilization of all components of waste HA, introduced a novel approach for monitoring and controlling harmful substances and reducing white pollution. This has significant implications for promoting sustainable development and recovering valuable resources.

Intranasally administered thermosensitive gel for brain-targeted delivery of rhynchophylline to treat Parkinson's disease.

The aim of this study is to overcome the obstacle of the blood-brain barrier (BBB) in therapeutic drugs of Parkinson's disease (PD), like rhynchophylline (RIN) entry by intranasal administration and to solve the problem of short residence time of drugs in the nasal cavity by the dosage form design of thermosensitive gel. We first conducted a study of the screening of absorption enhancers and 3% hydroxypropyl-ß-cyclodextrin (HP-ß-CD) was effective to improve the nasal mucosal permeability of RIN. By adjusting the ratio of different components in order to make the gel with adhesion and rapid gelation which were determined to be Poloxamer 407 (P407) 20%, Poloxamer 188 (P188) 1%, polyethylene glycol 6000 (PEG-6000) 1% and HP-ß-CD 3%. In addition, the characterization showed that the thermosensitive gel was network cross-linked, rapidly gelation upon entry into the nasal cavity and was stable as semi-solid state with adhesion as well as sustained release properties. Moreover, pharmacokinetic study was performed to evaluate the bioavailability and brain targeting of RIN thermosensitive gel and which were 1.6 times and 2.1 times higher than those of oral administration. We also evaluated the anti-PD effects of RIN thermosensitive gel in-vitro as well as in-vivo. The results showed that RIN thermosensitive gel was effective in repairing the motor function impairment, dysregulated expression levels of oxidative stress factors, and positive neuronal damage within the substantia nigra and dopamine caused by PD. The constructed intranasal drug administration strategy through thermosensitive gel provided a new choice for targeted treatment of PD together with other central nervous system diseases.

A pH-responsive, endosomolytic liposome functionalized with membrane-anchoring, comb-like pseudopeptides for enhanced intracellular delivery and cancer treatment.

Low intracellular delivery efficiency and multidrug resistance are among major barriers to effective cancer therapy. Herein, we report a novel, virus-mimicking, endosomolytic liposomal drug-delivery platform to address these two key challenges. The pH-responsive, comb-like pseudopeptides were prepared by grafting relatively long alkyl side chains onto a polyamide, poly(L-lysine isophthalamide), to mimic fusogenic peptides in viral spikes. The cholesterol-containing liposome, which mimics the viral envelope, was readily coated with these pseudopeptides due to their hydrophobic side chains acting as membrane anchors. These endosomolytic pseudopeptides displayed high adsorption onto the liposomal membrane and enabled the significantly higher cellular uptake. The virus-mimicking system showed a pH-triggered content-release profile which could be manipulated by varying the structure and concentration of the adsorbed polymers. The endosomolytic ability of the multifunctional liposome and its use for efficient intracellular delivery of the widely used anticancer drug doxorubicin (DOX) were demonstrated. The virus-mimicking liposomal system with DOX encapsulation exhibited considerably higher potency against HeLa cervical cancer cells, A549 lung cancer cells, MES-SA uterus cancer cells, and MES-SA/DX5 multidrug-resistant cancer cells than DOX-loaded bare liposomes and free DOX. These results suggest its potential applications for enhanced cytoplasmic delivery and cancer treatment.

Plasmon induced dual excited synergistic effect in Au/metal-organic frameworks composite for enhanced antibacterial therapy.

Efficient antibacterial therapy holds great promise for human health. However, it is often limited by the insufficient activity of antibacterial agents. Herein, we demonstrate that the localized surface plasmon resonance (LSPR) excitation of gold nanostars (AuNSs) can dramatically improve the antibacterial activity of a Zn-metal-organic frameworks (Zn-MOFs) nanosheet, which exhibits higher ability to generate reactive oxygen species (ROS) (∼2.5-fold) for bacterial inactivation under light irradiation. Mechanistic investigations demonstrate that the enhancement is closely related to a plasmon-induced "dual excited synergistic effect". On the one hand, the Zn-MOFs nanosheets as photosensitive agents can be excited to generate ROS with bacterial toxicity. More importantly, abundant plasmonic hot electrons are generated on the surface of AuNSs upon LSPR excitation, which are then transferred from AuNSs into the Zn-MOFs due to the energy matching. As a result, the Zn-MOFs nanosheet presents an electron-rich condition, which activates the adsorbed O2 molecule into a transition state followed by its decomposition into ROS for bacterial inactivation. This study highlights the superiority of LSPR excitation on improving the antibacterial activity of MOFs and provides a novel strategy for effective antibacterial therapy.

CD44 targeted redox-triggered self-assembly with magnetic enhanced EPR effects for effective amplification of gambogic acid to treat triple-negative breast cancer.

Gambogic acid (GA) is a natural anti-tumor drug whose application is restricted by its poor aqueous solubility and inefficient bioavailability. Developing nanomaterials with excellent biocompatibility can amplify the therapeutic effects of GA. In this study, a tumor-targeted redox controllable self-assembled nano-system with magnetic enhanced EPR effects (mPEG-HA/CSO-SS-Hex/SPION/GA) was developed to improve the anticancer efficacy of GA. The nano-system is constituted by three layers: the outer layer is mono-aminated poly(ethylene glycol) grafted hyaluronic acid (mPEG-HA), which can target the CD44 receptor in breast cancer cells; the middle layer consists of disulfide linked hexadecanol (Hex) and chitosan oligosaccharide (CSO) to control the drug release by reduction response; the core layer is superparamagnetic iron oxide nanoparticles (SPION), which can enhance the EPR effect by magnetic guidance and contribute to GA entrapment. Different experiments were performed to characterize the complex self-assembly, and the cytotoxicity, pharmacokinetics, and in vivo antitumor activity of the self-assembly were investigated to evaluate its anti-tumor effects. The results revealed that mPEG-HA/CSO-SS-Hex/SPION/GA is an excellent nanosystem with appropriate size and sensitive responsiveness; it can accumulate in tumor sites and achieve excellent therapeutic effects on triple-negative breast cancer (TNBC). In summary, a CD44-targeted redox-triggered self-assembly nanosystem with magnetic enhanced EPR effects was developed for effective amplification of GA; it has potential to act as an effective carrier in drug delivery for chemotherapy of TNBC.