No abstract

In this work, we prepared quaternized carbon dots (CDs) with simultaneous antibacterial and bacterial differentiation capabilities using a simple carboxyl-amine reaction between lauryl betaine and amine-functionalized CDs. The obtained quaternized CDs have several fascinating properties/abilities: (1) A long fluorescence emission wavelength ensures the exceptional bacterial imaging capability, including the super-resolution imaging ability; (2) the polarity-sensitive fluorescence emission property leads to significantly enhanced fluorescence when the quaternized CDs interact with bacteria; (3) the presence of both hydrophobic hydrocarbon chains and positively charged quaternary ammonium groups makes the CDs selectively attach to Gram-positive bacteria, realizing the bacterial differentiation; (4) excellent antimicrobial activity is seen against Gram-positive bacteria with a minimum inhibitory concentration of 8 μg/mL for Staphylococcus aureus. Besides, the quaternized CDs are highly stable in various aqueous solutions and exhibit negligible cytotoxicity, suggesting that they hold great promise for clinical applications. Compared to the traditional Gram staining method, the selective Gram-positive bacterial imaging achieved by the quaternized CDs provides a much simpler and faster method for bacterial differentiation. In summary, by combining selective Gram-positive bacterial recognition, super-resolution imaging, and exceptional antibacterial activity into a single system, the quaternized CDs represent a novel kind of metal-free nanoparticle-based antibiotics for antibacterial application and a new type of reagent for efficient bacterial differentiation.

Chemodynamic therapy (CDT), a novel cancer therapeutic strategy defined as the treatment using Fenton or Fenton‐like reaction to produce •OH in the tumor region, was first proposed by Bu, Shi, and co‐workers in 2016. Recently, with the rapid development of Fenton and Fenton‐like nanomaterials, CDT has attracted tremendous attention because of its unique advantages: 1) It is tumor‐selective with low side effects; 2) the CDT process does not depend on external field stimulation; 3) it can modulate the hypoxic and immunosuppressive tumor microenvironment; 4) the treatment cost of CDT is low. In addition to the Fe‐involved CDT strategies, the Fenton‐like reaction‐mediated CDT strategies have also been proposed, which are based on many other metal elements including copper, manganese, cobalt, titanium, vanadium, palladium, silver, molybdenum, ruthenium, tungsten, cerium, and zinc. Moreover, CDT has been combined with other therapies like chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, and immunotherapy for achieving enhanced anticancer effects. Besides, there have also been studies that extend the application of CDT to the antibacterial field. This review introduces the latest advancements in the nanomaterials‐involved CDT from 2018 to the present and proposes the current limitations as well as future research directions in the related field.

Fenton reaction‐mediated chemodynamic therapy (CDT) can kill cancer cells via the conversion of H2O2 to highly toxic HO•. However, problems such as insufficient H2O2 levels in the tumor tissue and low Fenton reaction efficiency severely limit the performance of CDT. Here, the prodrug tirapazamine (TPZ)‐loaded human serum albumin (HSA)–glucose oxidase (GOx) mixture is prepared and modified with a metal–polyphenol network composed of ferric ions (Fe3+) and tannic acid (TA), to obtain a self‐amplified nanoreactor termed HSA–GOx–TPZ–Fe3+–TA (HGTFT) for sustainable and cascade cancer therapy with exogenous H2O2 production and TA‐accelerated Fe3+/Fe2+ conversion. The HGTFT nanoreactor can efficiently convert oxygen into HO• for CDT, consume glucose for starvation therapy, and provide a hypoxic environment for TPZ radical‐mediated chemotherapy. Besides, it is revealed that the nanoreactor can significantly elevate the intracellular reactive oxygen species content and hypoxia level, decrease the intracellular glutathione content, and release metal ions in the tumors for metal ion interference therapy (also termed “ion‐interference therapy” or “metal ion therapy”). Further, the nanoreactor can also increase the tumor’s hypoxia level and efficiently inhibit tumor growth. It is believed that this tumor microenvironment‐regulable nanoreactor with sustainable and cascade anticancer performance and excellent biosafety represents an advance in nanomedicine.

A simple and highly efficient method for dopamine (DA) detection using water-soluble silicon nanoparticles (SiNPs) was reported. The SiNPs with a high quantum yield of 23.6% were synthesized by using a one-pot microwave-assisted method. The fluorescence quenching capability of a variety of molecules on the synthesized SiNPs has been tested; only DA molecules were found to be able to quench the fluorescence of these SiNPs effectively. Therefore, such a quenching effect can be used to selectively detect DA. All other molecules tested have little interference with the dopamine detection, including ascorbic acid, which commonly exists in cells and can possibly affect the dopamine detection. The ratio of the fluorescence intensity difference between the quenched and unquenched cases versus the fluorescence intensity without quenching (ΔI/I) was observed to be linearly proportional to the DA analyte concentration in the range from 0.005 to 10.0 μM, with a detection limit of 0.3 nM (S/N = 3). To the best of our knowledge, this is the lowest limit for DA detection reported so far. The mechanism of fluorescence quenching is attributed to the energy transfer from the SiNPs to the oxidized dopamine molecules through Förster resonance energy transfer. The reported method of SiNP synthesis is very simple and cheap, making the above sensitive and selective DA detection approach using SiNPs practical for many applications.

Antibacterial photodynamic therapy (PDT), which enables effective killing of regular and multidrug-resistant (MDR) bacteria, is a promising treatment modality for bacterial infection. However, because most photosensitizer (PS) molecules fail to strongly interact with the surface of Gram-negative bacteria, this technique is suitable for treating only Gram-positive bacterial infection, which largely hampers its practical applications. Herein, we reveal for the first time that cholesterol could significantly facilitate the hydrophobic binding of PSs to the bacterial surface, achieving the hydrophobic interaction-based bacterial cell surface engineering that could effectively photoinactivate both Gram-negative and Gram-positive bacteria. An amphiphilic polymer composed of a polyethylene glycol (PEG) segment terminated with protoporphyrin IX (PpIX, an anionic PS) and cholesterol was constructed (abbreviated Chol-PEG-PpIX), which could self-assemble into micelle-like nanoparticles (NPs) in aqueous solution. When encountering the Gram-negative Escherichia coli cells, the Chol-PEG-PpIX NPs would disassemble and the PpIX moieties could effectively bind to the bacterial surface with the help of the cholesterol moieties, resulting in the significantly enhanced fluorescence emission of the bacterial surface. Under white light irradiation, the light-triggered singlet oxygen (O) generation of the membrane-bound PpIX could not only severely damage the outer membrane but also facilitate the entry of external Chol-PEG-PpIX into the bacteria, achieving >99.99% bactericidal efficiency. Besides, as expected, the Chol-PEG-PpIX NPs also exhibited excellent antibacterial performance against the Gram-positive Staphylococcus aureus. We also verified that this nanoagent possesses negligible dark cytotoxicity toward mammalian cells and good hemocompatibility. To the best of our knowledge, this study demonstrates for the first time the feasibility of constructing a fully hydrophobic interaction-based and outer membrane-anchored antibacterial PDT nanoagent.

The shape effect of gold (Au) nanomaterials on the efficiency of cancer radiotherapy has not been fully elucidated. To address this issue, Au nanomaterials with different shapes but similar average size (∼50 nm) including spherical gold nanoparticles (GNPs), gold nanospikes (GNSs), and gold nanorods (GNRs) were synthesized and functionalized with poly(ethylene glycol) (PEG) molecules. Although all of these Au nanostructures were coated with the same PEG molecules, their cellular uptake behavior differed significantly. The GNPs showed the highest cellular responses as compared to the GNSs and the GNRs (based on the same gold mass) after incubation with KB cancer cells for 24 h. The cellular uptake in cells increased in the order of GNPs > GNSs > GNRs. Our comparative studies indicated that all of these PEGylated Au nanostructures could induce enhanced cancer cell-killing rates more or less upon X-ray irradiation. The sensitization enhancement ratios (SERs) calculated by a multitarget single-hit model were 1.62, 1.37, and 1.21 corresponding to the treatments of GNPs, GNSs, and GNRs, respectively, demonstrating that the GNPs showed a higher anticancer efficiency than both GNSs and GNRs upon X-ray irradiation. Almost the same values were obtained by dividing the SERs of the three types of Au nanomaterials by their corresponding cellular uptake amounts, indicating that the higher SER of GNPs was due to their much higher cellular uptake efficiency. The above results indicated that the radiation enhancement effects were determined by the amount of the internalized gold atoms. Therefore, to achieve a strong radiosensitization effect in cancer radiotherapy, it is necessary to use Au-based nanomaterials with a high cellular internalization. Further studies on the radiosensitization mechanisms demonstrated that ROS generation and cell cycle redistribution induced by Au nanostructures played essential roles in enhancing radiosensitization. Taken together, our results indicated that the shape of Au-based nanomaterials had a significant influence on cancer radiotherapy. The present work may provide important guidance for the design and use of Au nanostructures in cancer radiotherapy.

Glutathione (GSH) can significantly and selectively enhance the fluorescence intensity of Au nanoclusters (NCs) prepared by blending HAuCl4 and histidine in solution. The quantum yield of the Au NCs after adding GSH can reach above 10%. Besides, GSH capping shifts the excitation peak of Au NCs from ultraviolet (386 nm) to visible light (414 nm) and improves the stability of the Au NCs. The cytotoxicities of the Au NCs with and without GSH for normal lung cells (ATII) and cancerous lung cells (A549) are evaluated. The GSH-capped Au NCs have much less cytotoxicity to both normal and cancer cells, as compared to those without GSH. For Au NCs without GSH, less cytotoxicity is observed in cancer cells than in normal cells. In addtion, the Au NCs can selectively detect GSH over cysteine and homocysteine, the two biothiols which commonly exist in cells that can seriously affect GSH detection. Most importantly, Au NCs without GSH can selectively image the cancer cells, especially for the liver cancer cells whose GSH content is much higher than other cell types. This property makes the Au NCs a powerful probe to distinguish cancer cells from normal cells.