Carbon dots (CDs) are nearly zero-dimensional fluorescent carbon nanomaterials, featuring excellent fluorescence (FL) properties, tunable optical characteristics, and good biocompatibility. These advantages make them uniquely advantageous in non-invasive tumor treatment. This review first introduces the principles of photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), and chemodynamic therapy (CDT). Secondly, it systematically elaborates on the application progress of PDT, PTT, SDT, and CDT in tumor treatment, among which the application of PDT in anti-tumor and antibacterial aspects is classified and elaborated. The unique feature of this review lies in its systematic classification of various treatment strategies, and it particularly emphasizes the synergistic effects of carbon dots in different therapies, highlighting the advantages of the multi-functional integrated platform in overcoming the limitations of single therapies.
Hirudin is a potent anticoagulant peptide whose clinical application is limited by scarce natural supplies and the suboptimal activity of recombinant versions from conventional microbial hosts lacking key post-translational modifications. Here, for the first time, we establish the “Generally Regarded as Safe” (GRAS) microalga, Chlamydomonas reinhardtii , as a novel biological chassis for producing fully functional hirudin. Using high-density heterotrophic fermentation, we generated a bioactive lyophilized algal powder suitable for oral delivery. Crucially, the algal-derived hirudin underwent proper tyrosine sulfation—a key modification absent in prokaryotic hosts—conferring exceptionally high thrombin-inhibitory activity (up to 20,000 ATU/mg). When orally administered to a murine thrombosis model, this hirudin-loaded alga demonstrated potent antithrombotic efficacy. It also exhibited a superior safety profile, showing no signs of the thrombocytopenia or bleeding associated with traditional anticoagulants. This study establishes a green, scalable biomanufacturing and oral delivery platform for therapeutics, highlighting transformative potential at the nexus of agricultural bioengineering, functional foods, and biomedicine. ### Competing Interest Statement The authors have declared no competing interest. the Natural Science Foundation for Distinguished Young Scholars of Hubei Province, 2025AFA060 the Wuhan Municipal Education Bureau's Program for the Integration of Research and Education, 2025KCJ03 the National Natural Science Foundation of China, 32170702
Targeting oxidative phosphorylation of bacteria is a novel antibiotic strategy leading to rapid cell death as a result of respiration suppress. Herein, a conductive polymer termed polypyrrole (PPy) is used to short-circuit the electron transfer chain (ETC) of bacteria cells owing to its higher electron affinity to electrons than all of the electron carriers on ETC. A hydrogel is fabricated using PPy which is anticipated to seize electrons from ETC and inhibit respiration of bacteria cells. The results show that the prepared PPy hydrogel can mediate an effective direct current (DC) antibacterial therapy which greatly enhances intracellular reactive oxygen species (ROS) level of Escherichia coli (E. coli), suppresses respiration, induces apoptosis-like cell death of E. coli accompanied by chromosomal condensation and loss of structural integrity, and rapidly cleared E. coli infection in vivo. Taken into the photothermal property of PPy, a combined direct current-photothermal therapy is developed which can enhance bacteria-killing effects with the assistance of an 808 nm laser. Our findings provide a new antibiotic strategy with metabolic pathway as a target.
The carnitine cycle is responsible for the transport of cytoplasmic fatty acids to the mitochondria for subsequent β-oxidation to maintain intracellular energy homeostasis. Recent studies have identified abnormalities in the carnitine cycle in various types of tumors; these abnormalities include the altered expression levels of carnitine cycle-related metabolic enzymes and transport proteins. Dysfunction of the carnitine cycle has been shown to influence tumorigenesis and progression by altering intracellular oxidative and inflammatory status or regulating tumor metabolic flexibility. Many therapeutic strategies targeting the carnitine cycle are actively being explored to modify the dysfunction of the carnitine cycle in patients with malignant tumors; such approaches include carnitine cycle-related enzyme inhibitors and exogenous carnitine supplementation. Therefore, here, we review the studies of carnitine in tumors, aiming to scientifically illustrate the dysfunction of the carnitine cycle in tumor progression and provide new ideas for further research.
This study investigates the effect of incorporating lavender microcapsules into flooring coatings on the surface properties of the flooring. The experimental results indicate that after adding lavender microcapsules, the flooring’s color, gloss, wear resistance, and hydrophobicity experienced slight changes, with a color difference (ΔE) below 2 units, gloss decreasing by 8%, and wear resistance reducing by approximately 5%. However, these changes were within an acceptable range. Chemical composition analysis confirmed the fragrance-releasing effect of the lavender microcapsules. Furthermore, scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) verified the structural integrity of the microcapsules and their effective fragrance release. This study demonstrates that the introduction of lavender microcapsules not only enhances the scent perception of the flooring but also achieves long-term fragrance release while maintaining its fundamental physical properties, highlighting its potential for practical applications.
The radiation-induced skin injury (RISI) remains a great challenge for clinical wound management and care after radiotherapy, as patients will suffer from the acute radiation injury and long-term chronic inflammatory damage during the treatment. The excessive ROS in the early acute stage and prolonged inflammatory response in the late healing process always hinder therapeutic efficiency. Herein, we developed an extracellular matrix (ECM)-mimetic multifunctional glycopeptide hydrogel (oCP@As) to promote and accelerate RISI repair via a dual-modulation strategy in different healing stages. The oCP@As hydrogel not only can form an ECM-like nanofiber structure through the Schiff base reaction but also exhibits ROS scavenging and DNA double-strand break repair abilities, which can effectively reduce the acute radiation damage. Meanwhile, the introduction of oxidized chondroitin sulfate, which is the ECM polysaccharide-like component, enables regulation of the inflammatory response by adsorption of inflammatory factors, accelerating the repair of chronic inflammatory injury. The animal experiments demonstrated that oCP@As can significantly weaken RISI symptoms, promote epidermal tissue regeneration and angiogenesis, and reduce pro-inflammatory cytokine expression. Therefore, this multifunctional glycopeptide hydrogel dressing can effectively attenuate RISI symptoms and promote RISI healing, showing great potential for clinical applications in radiotherapy protection and repair.
As a new degradable medical metal material, Mg–Zn alloy has been widely used in clinical application. However, its popularization and application are seriously restricted by poor corrosion performance in the biological liquid environment. For this reason, we added a relatively non-toxic element to the human body (Sn) to Mg–Zn alloy, and we prepared Mg–2Zn–3Sn ternary system alloy, which improved the corrosion resistance and mechanical properties of magnesium alloys. The microstructure and corrosion behavior of as-cast Mg–2Zn and Mg–2Zn–3Sn alloys were investigated systematically for future application as biodegradable implants. The microstructures of the as-cast Mg–2Zn and Mg–2Zn–3Sn alloys were analyzed by light microscopy (LM), scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), and energy-dispersive spectrum (EDS). Meanwhile, an electrochemical test and immersion test in Hank’s solution (simulated human body fluids) were carried out for the Mg–2Zn and Mg–2Zn–3Sn alloys. The results showed that the as-cast Mg–2Zn–3Sn alloys consisted of an a-Mg matrix and Mg2Sn phase. Compared with that in Mg–2Zn alloy, the amount of second phases in Mg–2Zn–3Sn alloy increased significantly, and the grains were refined (from 100–130 lm to 50–70 lm). The electrochemical test and immersion test in Hank’s solution revealed that the corrosion current of the Mg–2Zn alloy decreased by 114.51 lA cm, and the corrosion rate decreased by 54.3% with 3 wt% Sn addition, respectively. The addition of Sn effectively improves the corrosion resistance of the Mg–2Zn alloy. In addition, the mechanism of improvement by Sn addition for the corrosion properties of the Mg–2Zn alloy was discussed. Therefore, the results can provide theoretical and data support for the subsequent development of Mg–Zn–Sn alloys for biodegradable implants. Metallic materials have been widely used in clinic because of their high mechanical strength, good toughness, and easy processing and molding [1, 2]. Traditional medical metallic materials are mostly biological inert materials [3] and cannot be degraded by themselves after implantation. They need to be removed through the second surgery and will cause new pain and more medical expenses for patients. Magnesium alloy is becoming a new kind of biodegradable bone implant material due to its good biocompatibility, mechanical properties matching with bone tissue, and degradation and absorption in the human body [4–6]. However, the corrosion rate of commercial magnesium alloy is too fast, and its toughness and strength will fail seriously with the increase of implantation time, which greatly hinders the promotion and application of biomedical magnesium alloy. Alloying is one of the main ways to improve the properties of magnesium alloy [7]. Zn is an indispensable nutrient element for the human body and has Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s12598021-01823-z.
The lysyl oxidase (LOX) family, consisting of LOX and LOX-like proteins 1–4 (LOXL1–4), is responsible for the covalent crosslinking of collagen and elastin, thus maintaining the stability of the extracellular matrix (ECM) and functioning in maintaining connective tissue function, embryonic development, and wound healing. Recent studies have found the aberrant expression or activity of the LOX family occurs in various types of cancer. It has been proved that the LOX family mainly performs tumor microenvironment (TME) remodeling function and is extensively involved in tumor invasion and metastasis, immunomodulation, proliferation, apoptosis, etc. With relevant translational research in progress, the LOX family is expected to be an effective target for tumor therapy. Here, we review the research progress of the LOX family in tumor progression and therapy to provide novel insights for future exploration of relevant tumor mechanism and new therapeutic targets.
Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) mediated by nanozymes has been extensively studied both experimentally and theoretically, but the low catalytic efficiency due to insufficient H2O2 in the TME and the poor biodegradability of the nanozymes are still main challenges for clinical translation of nanozymes. Herein, we designed a H2O2 self-supplying nanozyme bearing glucose oxidase (GOX) and polyethyleneimine based on a degradable iron-doped phosphate-based glass (FePBG) nanomimic (FePBG@GOX), which can convert endogenous glucose into toxic hydroxyl radicals. The GOX loaded on the nanozyme can effectively consume glucose in tumor cells to produce a large amount of H2O2 to make up for the lack of H2O2 in the TME. Thereafter, enormous hydroxyl radicals, based on a Fenton reaction of FePBG without any exogenous H2O2, are generated to induce severe apoptosis of tumor cells. The nanozyme exhibits enhanced in vitro cytotoxicity in a high-glucose medium than in a low-glucose medium, illustrating sufficient generation of H2O2 by GOX. The excellent in vivo antitumor efficacy is manifested by a high tumor growth inhibition ratio of 94.65% in model mice. Excellent intrinsic biodegradability owing to its phosphate-based glass nature is a remarkable advantage of the prepared FePBG nanozyme over most other reported nanozymes. Big concerns about side effects caused by long-time residence in living organisms are eliminated since it degrades not only in an acid medium but also in a neutral physiological environment. Therefore, this novel strategy of the TME-responsive H2O2 self-supplying nanozyme based on an endogenous cascade catalytic reaction opens up an avenue for designing degradable nanozymes in CDT.
The major challenge in the field of antibacterial agents is to overcome the low-permeability of bacteria cell membranes that protects the cells against diverse drugs. In this work, water-soluble polyaniline (PANI)-poly (p-styrenesulfonic acid) (PSS) (PANI:PSS) is found to spontaneously penetrate bacteria cellular membranes in a non-disruptive way, leaving no evidence of membrane poration/disturbance or cell death, thus avoiding side effects caused by cationic ammonia groups in traditional ammonia-containing antibacterial agents. For aqueous synthesis, which is important for biocompatibility, the polymer is synthesized via an enzyme-mimetic route relying on the catalysis of a nanozyme. Owing to its fluorescent properties, the localization of as-prepared PANI:PSS is determined by the confocal microscope, and the results confirm its rapid entry into bacteria. Under 808 nm near-infrared (NIR) irradiation, the internalized PANI:PSS generates local hyperthermia and destroys bacteria highly efficiently from inside the cells due to its excellent photothermal effects. Staphylococcus aureus (S. aureus), Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) could be effectively eliminated as well as the corresponding bacterial biofilms. Results of in vivo antibacterial experiments demonstrate excellent antibacterial activities of the water-soluble PANI:PSS without side effects. Therefore, the prepared water-soluble polymer in this study has great potential in the treatment of various bacterial infections.
Copper-containing antimicrobials are highly valuable in the field of medical disinfectants owing to their well-known high antimicrobial efficacy. Artificially synthesized nanozymes which can increase the level of reactive oxygen species (ROS) in the bacterial system have become research hotspots. Herein, we describe the design and fabrication of degradable Cu-doped phosphate-based glass (Cu-PBG) nanozyme, which can achieve excellent antibacterial effects against Gram-positive and Gram-negative bacteria. The antibacterial mechanism is based on the generation of ROS storm and the release of copper. It behaves like a peroxidase in wounds which are acidic and exerts lethal oxidative stress on bacteria via catalyzing the decomposition of H2O2 into hydroxyl radicals (•OH). Quite different from any other reported nanozymes, the Cu-PBG is intrinsically degradable due to its phosphate glass nature. It gradually degrades and releases copper ions in a physiological environment, which further enhances the inhibition efficiency. Satisfactory antibacterial effects are verified both in vitro and in vivo. Being biodegradable, the prepared Cu-PBG exhibits excellent in vivo biocompatibility and does not cause any adverse effects caused by its long-time residence time in living organisms. Collectively, these results indicate that the Cu-PBG nanozyme could be used as an efficient copper-containing antimicrobial with great potential for clinical translation.
The elimination of reactive oxygen species (ROS) caused by glutathione (GSH) is a fundamental concern in the oxidative stress therapy (OST) of tumors. This is the first report of copper phosphate nanospheres coated by poly (ethylene glycol) diacrylate (Cu3(PO4)2@PEGDA) which act as nanozymes to amplify the anti-tumor effects of OST. Cu3(PO4)2@PEGDA not only catalyzes the generation of ˙OH from H2O2 but also consumes GSH, which is counterproductive to the role of ˙OH. Moreover, the photothermal properties of Cu3(PO4)2@PEGDA further enhances the outcome of the OST when exposed to an 808 nm laser. Another novelty lies in that a new PEGylation strategy of peroxidase-like nanozymes is proposed, in which the Cu3(PO4)2 cores work as internal heaters and radical generators, which are necessary to initiate the radical polymerization of PEGDA. An elaborate core-shell nanostructure is obtained since the polymerization prefers to take place in the vicinity of the cores, overcoming the drawbacks of traditional PEGylation methods which include invalid polymerization far away from the cores and easy core-shell disassembly during applications.
A rationally designed multifunctional polydopamine (PDA)-coated metal-organic frameworks (MOFs) biosensors for detection of miRNA-122 with Zn2+-triggered aggregation-induced enhancement (AIE) and synergistic chem-photothermal therapy in vitro was developed for the first time. Further, it was successfully used for enhanced fluorescence imaging of miRNA-122 in living cells. The pH-responsive MOFs structure was decomposed under the influence of acidic environment, and a large amount of free Zn2+ was released as the trigger agent for AIE signal amplification, realizing the ultra-sensitive detection of miRNA-122 and the accurate discrimination of the cells with different expression levels of miRNA-122, with the detection limit as low as 12.5 pM. Meanwhile, ZIF-8 nanoparticles with high loading rate can effectively deliver therapeutic drugs to achieve responsive release. In addition, the modification of versatile PDA-coating provides the biosensor with a faster drug release capability and photothermal conversion performance, demonstrating its superior synergistic chem-photothermal therapy performance. It is expected to play an important role in the integration of cancer diagnosis and synergistic therapy.
Radiotherapy (RT) combined with chemotherapy remains a dominant therapeutic manner in clinical tumor treatment, which is irreplaceable in a short term. To seek an intrinsic connection of combined chemoradiation therapy and maximize the antitumor efficacy, we developed a reactive oxygen species (ROS)-sensitive nanomicelle drug delivery system based on a self-assembled amphiphilic polymer, hyaluronic acid-graft-poly-(propylene sulfide) (HA-PPS). A chemical radiosensitizer, doxorubicin (DOX), was encapsulated into the core of HA-PPS nanomicelles, constituting the DOX-loaded nanomicelles (HA-PPS@DOX NMs) with a spherical structure of around 205.10 ± 11.33 nm diameter with a narrow polydispersity index (PDI) of 0.135 ± 0.01. When combined with RT, the ROS-sensitive HA-PPS@DOX NMs disintegrated and released great drug cargos, which further enhanced cytotoxicity. Meanwhile, as a radiosensitizer, the released DOX sensitized cancer cells to radiotherapy, which has been confirmed by an enhanced sensitizer enhancement ratio (SER) value of 1.78 contributing to the increased cytotoxicity of concurrent chemoradiation tumor therapy, as evidenced by the improvement of half maximal inhibitory concentration (IC50 value) of DOX from 2.316 to 0.8235 μg/mL. Moreover, in vivo studies revealed that HA-PPS@DOX NMs exhibited prolonged circulation time and improved tumor accumulation. Particularly, the released DOX triggered by radiation strengthened radiotherapy sensitization in return. Consequently, these superiorities of HA-PPS@DOX NMs shown by the concurrent chemoradiation tumor therapy resulted in an ideal tumor inhibition rate of 70.4%, thus providing a promising ROS-sensitive nanomedicine for cancer treatment.
Establishing a stable, reliable and sensitive assay for the direct analysis in trace serum is of significance for the medical diagnosis and disease monitoring. We develop a MnO2 shell-isolated SERS nanoprobe (Au-Mpy-AuMnO2, AMAM) for the quantitative detection of alkaline phosphatase (ALP) in trace serum. Due to the physical isolation of MnO2 shell, AMAM is equipped with high stability, rarely happening the accidental aggregation. Particularly, the SERS signal is regulated by the etching of MnO2 shell, requiring not to change the local electromagnetic field or the molecular structure of Raman reporter (4-mercaptopyridine (Mpy)). Designating MnO2 shell as the Raman reference and the ratio of I-Mpy/I-MnO2 as the response signal, AMAM system can obviously eliminate the experimental interference and achieve highly reliable SERS quantification for ALP. This ratiometric SERS system exhibits good reproducibility, high stability and sensitivity for the ALP analysis. AMAM system is able to perform the colorimetric and SERS dual-readout detection, which displays a wide linear dynamic range (0.1-70 U/L) for ALP with a detection limit of 0.079 U/L. Additionally, integrating with in-capillary SERS technique, our proposed nanoprobe is also applicable of direct SERS analysis in trace undiluted human serum (2 mu L).
The accurate and sensitive detection of hydrogen peroxide (H2O2) is of practical significance in the fields of bioanalysis, medicine, environmental protection as well as food industry. Herein, we design and fabricate NaTb (SO4)2 nanoparticles (NPs) as novel fluorescent nanoprobes for H2O2 detection. The design strategy is based on the fluorescence quenching occurred during the oxidation of Tb(III) to Tb(IV) upon H2O2 addition. The sensing of NaTb(SO4)2 NPs to H2O2 is in a "turn-off" mode, and the sensitivity is tunable by the pH due to the pHdependence of the oxidizing ability of H2O2. Superior to most of the reported H2O2 sensors, NaTb(SO4)2 NPs exhibit reliable stability in acidic environment and a more sensitive response to H2O2 with a limit of detection (LOD) down to 0.047 mu M at pH = 3.2. Based on its high sensitivity and reliable stability, the NaTb(SO4)2 NPs is anticipated to find potential applications in the field of biosensors.
The present study reports an aqueous synthesis approach towards Cu-In-Se/ZnS quantum dots with emission in the near-infrared spectral range. The photoluminescence of the dots can be effectively controlled by adjusting the sulfur source, to achieve increased quantum yields (four times higher) and red-shifted emission peaks (from 809 nm to 830 nm).
Gold nanodevices have attracted extensive interest in the detection of specific targets within cells. However, constructing gold sensing devices that can be activated by the simulation of remote applications remains a huge challenge. Here, we report a Au nanoparticle (AuNP)-capped cage fluorescent biosensor based on controlled-release and Exonuclease III (Exo III) assisted cyclic enzymatic amplification that can be activated by adenosine triphosphate (ATP). In the system, AuNPs were used as the building blocks to cap the pores of Au nanocages (AuNCs) loaded with Rhodamine B (RhB) molecules through the hybridization of DNA. The RhB fluorescent molecules were finally released with the help of Exo III in the presence of ATP for detection purposes. Ultimately, the biosensor leads to a wide linear ATP detection range from 1.0 × 10-9 to 1.0 × 10-7 M with a limit of detection (LOD) down to 0.88 nM. In addition, it also has good selectivity for ATP to distinguish between ATP and ATP analogues such as cytidine triphosphate (CTP), guanosine triphosphate (GTP), and uridine triphosphate (UTP). Therefore, as a convenient and sensitive biosensor, it is expected to be widely used in the biomedical field.
The CRB–FFF–cyclen could transform into a hydrogel via a heating–cooling process. The resulting hydrogel could be protonated in a tumor environment, which is beneficial for cellular uptake and anti-tumor activity.
For SERS analysis in living cells, the inevitable desorption of Raman molecule on the substrate surface is a key challenge. To ensure high stability, SERS systems with Raman molecules protected inside the core-Raman molecule-shell (C-M-S) structures have been designed, but at the expense of sacrificed sensing performances. Here a shell-switchable SERS blocking strategy is developed for the reliable SERS analysis in living cells, relying on the shell blockers to regulate the SERS sensing signal without affecting the internal Raman molecules. After several C-M-S structures were investigated, the SERS blocking mechanism confirmed that thick shells (Au, Ag, ZnO, and MnO2) can cause a significant reduction in the internal SERS signal by obstructing the penetration of the laser or signal. The CAu-Mpy-SAu-SMnO2 nanoprobe is designed for the ratiometric SERS sensing in living cells, which retains sensing performances even though the Raman molecule is protected inside the nanostructure. This SERS strategy makes the turn-on sensing achievable in living cells with the MnO2 shell as a signal switch and a Raman reference. Additionally, it allows for accurate monitoring of the degradation of MnO2 carriers in living cells, even without fluorescent labels.