Photodynamic therapy (PDT) has long been shown to be a powerful therapeutic modality for cancer. However, PDT is undiversified and has become stereotyped in recent years. Exploration of distinctive ...PDT methods is thus highly in demand but remains a severe challenge. Herein, an unprecedented 1+1+1>3 synergistic strategy is proposed and validated for the first time. Three homologous luminogens with aggregation‐induced emission (AIE) characteristics were rationally designed based on a simple backbone. Through slight structural tuning, these far‐red/near‐infrared AIE luminogens are capable of specifically anchoring to mitochondria, cell membrane, and lysosome, and effectively generating reactive oxygen species (ROS). Notably, biological studies demonstrated combined usage of three AIE photosensitizers gives multiple ROS sources simultaneously derived from several organelles, which gives superior therapeutic effect than that from a single organelle at the same photosensitizers concentration. This strategy is conceptually and operationally simple, providing an innovative approach and renewed awareness of improving therapeutic effect through three‐pronged PDT.
Power of three: A synergistic enhanced photodynamic therapy (PDT) strategy was developed that concurrently acts on multiple subcellular organelles. At the same photosensitizer concentration, combined PDT treatment with three aggregation‐induced emission luminogens (AIEgens) exhibits superior therapeutic effect than that of single AIEgens.
Nucleic acid (NA)‐based therapy is proposed to address serious diseases such as cardiovascular diseases (CVDs). Powerful NA delivery vehicles are essential for effective gene therapy. Herein, a novel ...type of delivery vehicle, an unlockable core–shell nanocomplex (Hep@PGEA) with self‐accelerating NA release, is structurally designed. Hep@PGEA is composed of disulfide‐bridged heparin nanoparticle (HepNP) core and low‐toxicity PGEA cationic shell. In comparison with NA, heparin, a negatively charged polysaccharide macromolecule, exhibits stronger interactions with cationic species. Upon the breakdown of redox‐responsive HepNP cores, unlocked heparin would interact with the outer cationic shells and replace the condensed NA to facilitate NA release. Such unique Hep@PGEA is successfully explored for effective miRNA–pDNA staged gene therapy of myocardial infarction (MI), one of the most serious CVDs. With the progression of MI, glutathione amounts in heart tissues increase. MiR‐499 (for the inhibition of cardiomyocyte apoptosis) and plasmid encoding vascular endothelial growth factor (for the promotion of angiogenesis) are sequentially delivered for systemic treatment of MI. Such treatment produces impressive results in restoring heart function and suppressing cardiac hypertrophy. Due to the wide existence of redox agents in cells, the proposed unlockable delivery nanovehicle and staged therapy strategy can provide new methods to effectively treat different serious diseases.
Unlockable core–shell nanocomplexes with self‐accelerating nucleic acid release are structurally designed as a novel type of delivery vehicle. The newly designed unlockable vector is successfully utilized for effective miRNA–pDNA staged gene therapy of serious cardiovascular diseases.
In recent ten years, 3D printing technology has been developed rapidly. As an advanced technology, 3D printing has been used to fabricate complex and high-precision objects in many fields. 3D ...printing has several technologies. Among these technologies, photo-curing 3D printing was the earliest and most mature technology. In 1988, the first 3D printing machine which was based on photo-curing and called Stereo lithography Appearance (SLA) technology was produced by 3D system Corp. After 30 years of development, many new technologies based on photocuring mechanism emerged. Based on the different principle of pattern formation and character of printing technology, numerous photocuring 3D printing techniques, such as SLA, DLP, LCD, CLIP, MJP, two-photon 3D printing, holographic 3D printing and so on, have been developed. Photo-curing 3D printing has many advantages, such as high precision, smooth surface of printing objects, rapid printing speed and so on. Here, we would introduce five industrial photocuring 3D printing technologies, which are SLA, DLP, LCD, CLIP and MJP. The characters of the materials and the progress of the application of the technique in the biomedical field is also overviewed. At last, the difficulties and challenges of photo-curing 3D printing are also discussed.
•Different techniques of photocuring 3D printing were overviewed.•The advantage, disadvantage and application of the different techniques of photocuring 3D printing were discussed.•The progress of photocuring 3D printing technique in biomedical application is commented.•The existing problems and challenges of photocuring 3D printing were presented.
•Application of green manure and/or rice straw increased rice yield compared with F.•The FMS combined the advantages of FM and FS in improving soil fertility.•The FMS had the greatest effect on soil ...microbial community and enzyme activities.•Straw had more lasting effects on soil properties and rice yield than green manure.
The cultivation of green manure or rice straw returns in southern China increases crop yields and soil fertility. Few studies have reported the effects of combining both management techniques on rice performance and soil fertility. A 3-year field study was carried out to analyse the impacts of the co-incorporation practice on soil microbial and biochemical parameters as well as crop yield. Five treatments were tested: (i) no-fertilizer (CK); (ii) chemical fertilizer (F); (iii) F plus green manure (FM); (iv) F plus rice straw (FS); (v) F plus green manure plus rice straw (FMS). The results showed that incorporation of green manure and/or rice straw increased double rice yields by 4.1% (FM), 4.7% (FS) and 9.6% (FMS) compared with F. The FMS treatment enhanced soil organic C (SOC), total N (TN), mineral N (Nmin), and available K (AK) levels by combining the advantage of FM in increasing TN and Nmin and the advantage of FS in increasing SOC and AK in comparison with F. The incorporation of green manure and/or rice straw stimulated microbial growth (total phospholipid fatty acids, PLFAs) and altered the soil microbial community structure relative to F, in which FMS had the greatest effect. The enzyme activities of β-glucosidase, β-cellobiosidase, N-acetyl-glucosaminidase, L-leucine aminopeptidase and phosphatase were higher in the green manure and/or rice straw application treatments than in the F treatment in the order FM ≈ FS < FMS. The partial least squares path model (PLS-PM) analysis indicated that green manure mainly influenced the abovementioned indices in the early rice season, while the effects of rice straw lasted until the late rice season. Our results suggest that co-incorporation of green manure and rice straw is a more effective practice for improving soil fertility and rice yields.
The advent of click chemistry has had a profound impact on many fields and fueled a need for reliable reactions to expand the click chemistry toolkit. However, developing new systems to fulfill the ...click chemistry criteria remains highly desirable yet challenging. Here, we report the development of light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) as a photoclick reaction via primary amines as direct click handle, to rapid and modular functionalization of diverse small molecules and native biomolecules. With intrinsic advantages of temporal control, good biocompatibility, reliable chemoselectivity, excellent efficiency, readily accessible reactants, operational simplicity and mild conditions, the PANAC photoclick is robust for direct diversification of pharmaceuticals and biorelevant molecules, lysine-specific modifications of unprotected peptides and native proteins in vitro, temporal profiling of endogenous kinases and organelle-targeted labeling in living systems. This strategy provides a versatile platform for organic synthesis, bioconjugation, medicinal chemistry, chemical biology and materials science.
Microenvironment‐responsive supramolecular assemblies have attracted great interest in the biomedical field due to their potential applications in controlled drug release. In this study, ...oxidation‐responsive supramolecular polycationic assemblies named CPAs are prepared for nucleic acid delivery via the host–guest interaction of β‐cyclodextrin based polycations and a ferrocene‐functionalized zinc tetraaminophthalocyanine core. The reactive oxygen species (ROS) can accelerate the disassembly of CPA/pDNA complexes, which would facilitate the release of pDNA in the complexes and further benefit the subsequent transfection. Such improvement in transfection efficiency is proved in A549 cells with high H2O2 concentration. Interestingly, the transfection efficiencies mediated by CPAs are also different in the presence or absence of light in various cell lines such as HEK 293 and 4T1. The single oxygen (1O2), produced by photosensitizers in the core of CPAs under light, increases the ROS amount and accelerates the disassembly of CPAs/pDNA complexes. In vitro and in vivo studies further illustrate that suppressor tumor gene p53 delivered by CPAs exhibits great antitumor effects under illumination. This work provides a promising strategy for the design and fabrication of oxidation‐responsive nanoassemblies with light‐enhanced gene transfection performance.
Oxidation‐triggered nanoassemblies named CPAs are prepared for high‐performance nucleic acid delivery. CPAs produce enhanced gene transfection efficiency due to their disassembly induced by illumination and H2O2 in the tumor environment, which is utilized for effective gene therapy in 4T1‐based cancer.
In this work, Zn-Co-ZIF-n(shell)/PAN(core) nanofibers were well-designed and prepared through bimetal zeolitic imidazolate frameworks (ZIFs) grown on the surface of ...2-Methylimidazole/Polyacrylonitrile (MIM/PAN) electrospun nanofibers. After carbonization of Zn-Co-ZIF-n/PAN nanofibers (n was the molar ratio of Zn/Co before carbonization), the core layer was converted to nitrogen-doped carbon nanofibers (NCNFs) and the shell layer was converted to Zn/Co bimetal nanoparticles coated with graphitic carbon layer (Zn/Co@C). It was found that Zn/Co@C-NCNFs are featured with hierarchical network structure and high surface area. Further doped by nitrogen species and embedded by Zn/Co bimetal nanoparticles, it exhibited excellent electrocatalytic performance for oxygen reduction reaction (ORR), better than the reference samples. By further investigating the electrocatalytic performance, the optimized sample Zn/Co@C-NCNFs (0.50) derived from Zn-Co-ZIF-0.50/PAN at 800 °C carbonization exhibited excellent electrocatalytic activity (the onset and half-wave potentials were −0.099 V and −0.20 V vs. Ag/AgCl, respectively and nearly four electron selectivity (3.69)). Moreover, its methanol tolerance and duration stability was better than that of the commercial 20 wt% Pt/C. It provides an effective strategy to design non-precious metal electrocatalysts from the Zn-Co-ZIF-n/PAN nanofibers or other MOFs/polymer nanofibers for ORR in fuel cells.
The preparation process included three steps: Firstly, MIM/PAN nanofibers were prepared by electrospinning; Secondly, the nucleation and growth of Zn-Co-ZIF-n produced along the nanofiber surfaces; Lastly, Zn/Co@C-NCNFs were prepared by carbonization of Zn-Co-ZIF-n/PAN nanofibers. The colour of nanofiber film changed from white to purple, and finally became black in the preparation process. Display omitted
Core-shell structured PEO/HA nanofibers could be produced from electric field inducing phase separation during the electrospinning progress. Hyaluronic acid (HA) molecules could move along the ...opposite direction of the electric field under the electrostatic force, which induced phase separation from PEO to form the core layer of nanofibers. The morphology of core–shell nanofibers was supported using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Thermal analysis and X-ray diffraction (XRD) results showed that the fibers had good thermal stability and HA hindered the crystallization of the PEO. The presence of PEO on the surface was also verified by X-ray photoelectron spectroscopy (XPS) analysis as further evidence of core–shell formation during the process of electrospinning. Methylthiazolydiphenyl-tetrazolium bromide (MTT) assay was employed to investigate the toxic and cytocompatibility with the aim of demonstrating the possible application for tissue engineering scaffolds. Furthermore, In vitro cytotoxicity against fibroblasts cells culture demonstrated the nanofibers as scaffolds were biocompatible and nontoxic.
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•PEO/HA core–shell nanofibers are prepared via electrospinning.•Electric field induces phase separation during the electrospinning.•Hyaluronic acid would move in the opposite direction.
Osteosarcoma (OS) is the most common bone malignancy without a reliable therapeutic target. Glypican‐3 (GPC3) mutation and upregulation have been detected in multidrug resistant OS, and anti‐GPC3 ...immunotherapy can effectively suppress the growth of organoids. Further profiling of GPC3 mutations and expression patterns in OS is of clinical significance. To address these issues, fresh OS specimens were collected from 24 patients for cancer‐targeted next‐generation sequencing (NGS) and three‐dimensional patient‐derived organoid (PDO) culture. A tumor microarray was prepared using 37 archived OS specimens. Immunohistochemical (IHC) staining was performed on OS specimens and microarrays to profile GPC3 and CD133 expression as well as intratumoral distribution patterns. RT‐PCR was conducted to semiquantify GPC3 and CD133 expression levels in the OS tissues. Anti‐GPC3 immunotherapy was performed on OS organoids with or without GPC3 expression and its efficacy was analyzed using multiple experimental approaches. No OS cases with GPC3 mutations were found, except for the positive control (OS‐08). IHC staining revealed GPC3 expression in 73.77% (45/61) of OSs in weak (+; 29/45), moderate (++; 8/45), and strong (+++; 8/45) immunolabeling densities. The intratumoral distribution of GPC3‐positive cells was variable in the focal (+; 10%–30%; 8/45), partial (++; 31%–70%; 22/45), and the most positive patterns (+++; >71%; 15/45), which coincided with CD133 immunolabeling (P = 9.89 × 10−10). The anti‐GPC3 antibody efficiently inhibits Wnt/β‐catenin signaling and induces apoptosis in GPC3‐positive PDOs and PDXs, as opposed to GPC3‐negative PDOs and PDXs. The high frequency of GPC3 and CD133 co‐expression and the effectiveness of anti‐wild‐type GPC3‐Ab therapy in GPC3‐positive OS models suggest that GPC3 is a novel prognostic parameter and a promising therapeutic target for osteosarcoma.
Lack of molecular target is a tricky problem in osteosarcoma treatment. In this study, we report (1) high frequency of GPC3 detection (73.77%; 45/61) and its overlapped expression with CD133 in OSs; (2) successful generation of patient‐derived organoids (PDOs) from 24 human osteosarcoma cases (OSs) as ex vivo experimental model; (3) the effectiveness of anti‐GPC3 strategy against GPC3‐expressing OS PDOs and PDXs, accompanied with suppressed Wnt/β‐catenin signaling. We therefor propose that GPC3 would be a promising target for personalized OS therapy.
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