Designing Nonconventional Luminescent Materials with Efficient Emission in Dilute Solutions via Modulation of Dynamic Hydrogen Bonds.

Nonconventional luminescent materials (NLMs) which do not contain traditional aromatic chromophores are of great interest due to their unique chemical structures, optical properties, and their potential applications in various areas, such as cellular imaging and chemical sensing. However, most reported NLMs show weak or no emission in dilute solutions, which severely limits their applications. In this work, dynamic hydrogen bonds were utilized to design NLMs with efficient emission in dilute solutions. To further validate the results, polymers P1 and P2 were successfully prepared and investigated. It was found that the luminescence quantum efficiency of P1 and P2 at a concentration of 0.1 mg/mL in water solution was 8.9 and 0.6%, respectively. The high efficiency can be attributed to the fact that polymer P1 has more intra- or intermolecular dynamic hydrogen bonds and other short interactions than P2 in dilute solutions, allowing P1 to achieve the through-space conjugation effect to increase the degree of system conjugation, restrict molecular motion, and decrease nonradiative transitions, which can effectively improve luminescence. In addition, polymer P2 exhibits the characteristics of clustering-triggered emission, excitation wavelength-dependent and concentration-dependent fluorescence properties, excellent photobleaching resistance, low cytotoxicity, and selective recognition of Fe3+. The present study investigates the manipulation of luminescence properties of NLMs in dilute solutions through the modulation of dynamic hydrogen bonds. This approach can serve as a semi-empirical technique for designing and building innovative NLMs in the times ahead.

Synthesis of organic-solvent-soluble cellulose and preparation of fluorescent polyurethanes for the detection and removal of Hg+ ions.

Modifying cellulose to obtain materials with favorable processing properties and functions is highly significant, especially, for the detection and removal of heavy metal ions. In this study, fluorescent cellulose-based polyurethane (PU) films containing naphthalimide fluorophore were synthesized and could use for the convenient detection and removal of Hg+ ions. Firstly, the microcrystalline cellulose was treated with SOCl2 to convert some -OH groups into -Cl. Simultaneously, a naphthalimide derivative (NAN) with -NH- groups was synthesized. Subsequently, a fluorescent cellulose-based probe (Cel-NAN) was prepared by utilizing the substitution reaction between -Cl on cellulose and -NH- on NAN. Finally, two cellulose-based fluorescent PU films (Cel-NAN-PU1 and Cel-NAN-PU2) were successfully synthesized by reacting the unreacted -OH groups on Cel-NAN with PEG-1000 and HDI/IPDI. These as-prepared PU films could serve as portable fluorescence test papers to Hg+ ions in aqueous solutions. Upon contact with Hg+ ions, the fluorescence was quenched, acting as a "turn-off" probe. Simultaneously, these films could serve as adsorbents for the removal of Hg+ ions from aqueous systems. Cel-NAN-PU1 film exhibited a removal efficiency over 80 % and an adsorption capacity of 8.4 mg·cm-2 for Hg+. These cellulose-based fluorescent PU films possess promising potential in the field of mercury pollution control.

[Effects of Polyethylene Microplastics on Soil Nutrients and Enzyme Activities].

The threat of microplastic pollution in soil ecosystems has caused widespread concern. In order to clarify the effect of polyethylene microplastics on soil properties, a 4-month soil incubation experiment was conducted in this study to investigate the effect of different mass fraction (1 %, 2.5 %, and 5 %) and particle sizes (30 mesh and 100 mesh) of polyethylene microplastics on soil chemical properties, nutrient contents, and enzyme activities. The results showed that:① When the particle size was 100 mesh, microplastics at the mass concentrations of the 2.5 % and 5 % treatments significantly reduced soil pH, and the exposure of polyethylene microplastics had no significant effect on soil conductivity. ② Compared to that in CK, the addition of microplastics reduced soil available potassium, available phosphorus, and nitrate nitrogen to varying degrees. The addition of 100 mesh microplastics significantly increased soil organic matter and ammonium nitrogen. ③ When the particle size was 100 mesh, compared to that in CK, treatments of all concentrations significantly increased soil catalase activity and alkaline phosphatase, showing an increasing but not significant trend, and the 5 % concentration treatment significantly decreased soil sucrase activity. ④ Changes in soil properties were influenced by the addition of microplastics of different concentrations and sizes, with higher concentrations and smaller particle sizes having more significant effects. In conclusion, the effects of microplastics on soil properties were not as pronounced as expected, and future research should focus on the mechanisms involved in the different effects.

Mucoadhesive liposomal delivery system synergizing anti-inflammation and anti-oxidation for enhanced treatment against dry eye disease.

Dry eye disease (DED) is a common and frequent ocular surface disease worldwide, which can cause severe ocular surface discomfort and blurred vision. Inflammation and reactive oxygen species (ROS) play decisive roles in the development of DED. However, existing treatments usually focus on anti-inflammation while ignore the role of ROS in DED. Ever worse, the clinical preparations are easily cleared by nasolacrimal ducts, resulting in poor therapeutic effect. To circumvent these obstacles, here we designed a phenylboronic acid (PBA) modified liposome co-loading immunosuppressant cyclosporin A (CsA) and antioxidant crocin (Cro). The CsA/Cro PBA Lip achieved mucoadhesion through the formation of covalent bonds between PBA and the sialic acid residues on mucin, and consequently improved the retention of drugs on the ocular surface. By inhibiting ROS production and blocking NF-κB inflammatory pathway, CsA/Cro PBA Lip successfully promoted the healing of damaged corneal epithelium, eventually achieving the goal of relieving DED. CsA/Cro PBA Lip is proven a simple yet effective dual-drug delivery system, exhibiting superior antioxidant and anti-inflammatory effects both in vitro and in vivo. This approach holds great potential in the clinical treatment of DED and other related mucosal inflammations.

Organic-soluble chitosan-g-PHMA (PEMA/PBMA)-bodipy fluorescent probes and film by RAFT method for selective detection of Hg2+/Hg+ ions.

Chitosan as the plentiful and easily available natural polymer, its solubility in organic solvents is still a challenge. In this article, three different chitosan-based fluorescent co-polymers were prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. They could not only dissolve in several organic solvents, but also could selectively recognize Hg2+/Hg+ ions. Firstly, allyl boron-dipyrrolemethene (bodipy) was prepared, and used as one of the monomers in the subsequent RAFT polymerization. Secondly, chitosan-based chain transfer agent (CS-RAFT) was synthesized through classical reactions for dithioester preparation. Finally, three methacrylic ester monomers and bodipy bearing monomers were polymerized and grafted as branched-chains onto chitosan respectively. By RAFT polymerization, three chitosan-based macromolecular fluorescent probes were prepared. These probes could be readily dissolved in DMF, THF, DCM, and acetone. All of them exhibited the 'turn-on' fluorescence with selective and sensitive detection for Hg2+/Hg+. Among them, chitosan-g-polyhexyl methacrylate-bodipy (CS-g-PHMA-BDP) had the best performance, its fluorescence intensity could be increased to 2.7 folds. In addition, CS-g-PHMA-BDP could be processed into films and coatings. When loading on the filter paper, fluorescent test paper was prepared and it could realize the portable detection of Hg2+/Hg+ ions. These organic-soluble chitosan-based fluorescent probes could enlarge the applications of chitosan.

A novel method to prepare water-soluble cellulose-based fluorescent probes for highly sensitive and selective detection and removal of Hg2+/Hg22+ ions.

Improving the water solubility of natural product cellulose and using it to treat heavy metal ions is very important. In this work, cellulose-based fluorescent probes containing BODIPY fluorophore were synthesized by simple chemical method, which realized the selective recognition and removal of Hg2+/Hg22+ ions in an aqueous system. Firstly, fluorescent small molecule (BOK-NH2) bearing -NH2 group was synthesized through Knoevenagel condensation reaction between BO-NH2 and cinnamaldehyde. Secondly, via the etherification of -OH on the cellulose, substituents bearing -C ≡ CH groups with different lengths at the end are grafted on the cellulose. Finally, cellulose-based probes (P1, P2, and P3) were prepared by amino-yne click reaction. The solubility of cellulose is improved greatly, especially the cellulose derivative with branched long chains has excellent solubility in water (P3). Benefiting from the improved solubility, P3 could be processed into solutions, films, hydrogels, and powders. Upon the addition of Hg2+/Hg22+ ions, the fluorescence intensity enhanced, which are "turn-on" probes. At the same time, the probes could be utilized as efficient adsorbents for Hg2+/Hg22+ ions. The removal efficiency of P3 for Hg2+/Hg22+ is 79.7 %/82.1 %, and the adsorption capacity is 159.4 mg·g-1/164.2 mg·g-1. These cellulose-based probes are expected to be employed in the treatment of polluted environments.

Curbing Exosome Communications via Introducing Artificial Membrane Receptors for Metastatic Pancreatic Cancer Therapy.

Tumor-derived exosomes (TDEs) carry various biomolecular cargos and play crucial roles in metastasis. TDEs migrate to distal organs for intercellular communication and induce the formation of pre-metastatic niches (PMNs) to support tumor implantation and proliferation. Precise interference in the bioprocess of TDEs is expected to be efficacious for suppressing tumor metastasis. However, targeting both TDEs and the primary tumor is challenging. Here, based on metabolic glycoengineering and bio-orthogonal click chemistry, a two-step delivery strategy is designed to overcome this. During the first step, the tetraacetylated N-azidoacetyl-d-mannosamine-loaded nanoparticle responds to the metabolic activity of tumor cells in the primary tumor, tagging both tumor cells and TDEs with azide groups; dibenzyl-cyclootyne-modified nanoparticles then can, as the second step, specifically react with tumor cells and TDEs through a bio-orthogonal click reaction. This strategy not only inhibits tumor growth in pancreatic cancer models but also curbs the communicative role of TDEs in inducing liver PMNs and metastasis by tracking and downregulating the exosomal macrophage migration inhibitory factor.

Cucurbit[10]uril-mediated Supramolecular Assembly for Optically Tunable Dimers and Near White-light Emissive Materials.

Cucurbit[10]uril (Q[10]), the cucurbit[n]uril with a large cavity, exhibits several new features in the development of the host-guest complex. Thus, based on Q[10] and π-conjugated molecule, oligo(p-phenylenevinylene) derivative (OPVCOOH), the host-guest complexes with three different interaction ratios of 1 : 2, 2 : 2, and 3 : 2 assemblies (Q[10]: guest) were fabricated. Depending on the host/guest ratio, the emission color of these complexes ranged from blue to yellow-green. The extra Fe2+ coordinated with a bare carboxyl group of the Q[10]-OPVCOOH (3 : 2) assembly, obstructing its rotaxane structure and forming Q[10]-OPVCOOH-Fe2+ assembly, which may be used as a coating for near-white LED bulbs.

Metabolic reprogramming by dual-targeting biomimetic nanoparticles for enhanced tumor chemo-immunotherapy.

Cancer-associated fibroblasts (CAFs)-mediated metabolic support plays a vital role in tumorigenesis. The metabolic network between cancer cells and CAFs may serve as promising targets for cancer therapy. Here, aiming at targeted blockade of the metabolic support of CAFs to cancer cells, a biomimetic nanocarrier is designed by coating solid lipid nanoparticles containing chemotherapeutic paclitaxel (PTX) and glycolysis inhibitor PFK15 with hybrid membranes of cancer cells and activated fibroblasts. The nanoparticles possess outstanding dual-targeting ability which can simultaneously target cancer cells and CAFs. The encapsulated glycolysis inhibitor PFK15 can prevent the glycolysis of cancer cells and CAFs at the same time, thus increasing the chemosensitivity of cancer cells and blocking the metabolic support of CAFs to cancer cells. The results showed that the combination of PTX and PFK15 exhibited synergistic effects and inhibited tumor growth effectively. Moreover, the biomimetic nanoparticles obviously reduced the lactate production in the tumor microenvironment, leading to activated immune responses and enhanced tumor suppression. This work presents a facile strategy to destroy the metabolic network between cancer cells and CAFs, and proves the potential to elevate chemo-immunotherapy by glycolysis inhibition. STATEMENT OF SIGNIFICANCE: In many solid tumors, most cancer cells produce energy and carry out biosynthesis through glycolysis, even in aerobic conditions. As the main tumor stromal cells, cancer-associated fibroblasts (CAFs) usually turn oxidative phosphorylation into aerobic glycolysis with metabolic reprogramming and provide high-energy glycolytic metabolites for cancer cells. The metabolic network between cancer cells and CAFs is regarded as the vulnerability among cancer cells. Moreover, lactate produced by cancer cells and CAFs through glycolysis often leads to the immunosuppressive tumor microenvironment. The present study provides an effective approach to destroy the metabolic network between cancer cells and CAFs and greatly improves the antitumor immune response by reducing lactate production, which serves as a promising strategy for combined chemo-immunotherapy mediated by glycolysis.

A neutrophil-mediated carrier regulates tumor stemness by inhibiting autophagy to prevent postoperative triple-negative breast cancer recurrence and metastasis.

Recurrence and metastasis after resection are still the main challenges in clinical treatment of breast cancer. Residual tumor and cancer stem-like cells are the primary culprits of recurrence and metastasis. Recent research studies indicate that autophagy is a cytoprotective mechanism of tumors, which maintains the stemness of cancer cells and promotes tumor proliferation and metastasis. Here, we constructed a "Trojan horse" using neutrophils as the carrier (PH-RL@NEs) to prevent the recurrence and metastasis of postoperative breast cancer. Neutrophils, as a "Trojan horse," can quickly respond to postoperative inflammation and accurately deliver drugs to the residual tumor site. The inflammation-triggered "Trojan horse" was then opened to release the liposomes containing the chemotherapeutic drug paclitaxel (PTX) and the autophagy inhibitor hydroxychloroquine (HCQ). We found that HCQ could effectively inhibit tumor cell autophagy, interfere with tumor epithelial-mesenchymal transition, and reduce the tumor stem cell-like population. In the orthotopic 4T1 postoperative recurrence models, PTX and HCQ synergistically killed tumors and regulated the stemness of tumor cells, thereby significantly inhibiting tumor recurrence and metastasis. Our work proved that the inhibition of autophagy to reduce tumor stemness is feasible and effective, which opens up a new prospect for postoperative tumor treatment. STATEMENT OF SIGNIFICANCE: The present study aimed to solve the issues of postoperative recurrence and metastasis of breast cancer and low efficiency of drug administration after surgery. For this purpose, we constructed neutrophils containing hydroxychloroquine (HCQ) and paclitaxel (PTX) co-loaded liposomes (PH-RL@NEs), which for the first time regulated the stemness of tumor cells by inhibiting autophagy, thereby inhibiting postoperative recurrence and metastasis of breast cancer cells. The results showed that PH-RL@NEs enhanced the targeted drug delivery efficiency, with the help of postoperative inflammation chemotaxis of neutrophils. HCQ effectively inhibited autophagy of tumor cells and reduced tumor stem cell-like cells, thus improving the therapeutic effect in the 4T1 in situ postoperative recurrence model.

A "dual-guide" bioinspired drug delivery strategy of a macrophage-based carrier against postoperative triple-negative breast cancer recurrence.

Recurrence after tumor resection is mainly caused by post-operative inflammation and residual cancer cells, which is a serious obstacle to breast cancer treatment. Traditional nanoparticles rely primarily on the enhanced permeability and retention (EPR) effect in well-vascularized tumors. In this study, a macrophage-based carrier is designed to enhance the efficiency of targeting to recurrent tumors through a "dual-guide" strategy. After tumor resection, a burst of inflammatory factors occurs in the resection wound, which can recruit monocytes/macrophages rapidly. Combined with the tropism of monocyte chemoattractant protein, a large number of macrophage-mediated carriers will be recruited to surgical recurrence sites. Octaarginine (RRRRRRRR, R8)-modified liposomes in macrophages contain two agents with different pharmacological mechanisms, paclitaxel (PTX) and resveratrol (Res), which have enhanced therapeutic effects. In vitro study demonstrated that macrophage-mediated carriers approach 4 T1 cells through an inflammatory gradient and reach recurrence tumors through a "dual-guide" strategy. Then, membrane fusion and inflammation-triggered release deliver the drug into the recurrent tumor cells. In vivo experiments show that macrophage-based carriers exhibit effective tumor-targeting ability, especially in post-operation situations. More importantly, macrophage-mediated liposomes encapsulated with PTX and Res inhibit tumor recurrence in both ectopic and orthotopic 4 T1 post-operative recurrence models.