Cancer cells frequently exhibit resistance to various molecular and nanoscale drugs, which inevitably affects the drugs' therapeutic outcomes. Overexpression of glutathione (GSH) has been observed in many cancer cells, and solid evidence has corroborated the resulting tumor resistance to a variety of anticancer therapies, suggesting that this biochemical characteristic of cancer cells can be developed as a potential target for cancer treatments. The single treatment of GSH-depleting agents can potentiate the responses of the cancer cells to different cell death stimuli; therefore, as an adjunctive strategy, GSH depletion is usually combined with mainstream cancer therapies for enhancing the therapeutic outcomes. Propelled by the rapid development of nanotechnology, GSH-depleting agents can be readily constructed into anticancer nanomedicines, which have shown a steep rise over the past decade. Here, we review the common GSH-depleting nanomedicines which have been widely applied in synergistic cancer treatments in recent years. Some current challenges and future perspectives for GSH depletion-based cancer therapies are also presented. With the understanding of the structure−property relationship and action mechanisms of these biomaterials, we hope that the GSH-depleting nanotechnology will be further developed to realize more effective disease treatments and even achieve successful clinical translations.

Ultrasmall quaternized CDs are used to visualize Gram-positive and Gram-negative bacterial biofilms, and selectively eradicate and inhibit Gram-positive bacterial biofilms.

Bacterial infection has become an urgent health problem in the world. Especially, the evolving resistance of bacteria to antibiotics makes the issue more challenging, and thus new treatments to fight these infections are needed. Antibacterial photodynamic therapy (aPDT) is recognized as a novel and promising method to inactivate a wide range of bacteria with few possibilities to develop drug resistance. However, the photosensitizers (PSs) are not effective against Gram-negative bacteria in many cases. Herein, we use conjugated meso-tetra(4-carboxyphenyl)porphine (TCPP) and triaminoguanidinium chloride (TG) to construct self-assembled cationic TCPP-TG nanoparticles (NPs) for efficient bacterial inactivation under visible light illumination. The TCPP-TG NPs can rapidly adhere to both Gram-negative and Gram-positive bacteria and display promoted singlet oxygen ( 1 O 2 ) generation compared with TCPP under light irradiation. The high local positive charge density of TCPP-TG NPs facilitates the interaction between the NPs and bacteria. Consequently, the TCPP-TG NPs produce an elevated concentration of local 1 O 2 under light irradiation, resulting in an extraordinarily high antibacterial efficiency (99.9999% inactivation of the representative bacteria within 4 min). Furthermore, the TCPP-TG NPs show excellent water dispersity and stability during 4 months of storage. Therefore, the rationally designed TCPP-TG NPs are a promising antibacterial agent for effective aPDT.

We develop a general hydrothermal approach to fabricate new nanozymes with intrinsic peroxidase-like activity for H2O2 and glucose detection.

Bacterial infections, especially chronic infections caused by bacterial biofilms, have become a worldwide threat to public health. Encouragingly, the synergistic actions of two or more antibacterial drugs have been proven to be effective in treating refractory bacterial infections. Herein, we fabricated a robust antibacterial nanohybrid, the colistin-loaded polydopamine nanospheres (PDA NSs) decorated uniformly with small silver nanodots (u-CPSs), and the u-CPSs could realize synergistic bactericidal performance for combating bacterial infections. PDA NSs, as an adhesive nanocarrier, could bind to the bacterial surfaces, where the drugs (colistin and silver ions) on the PDA surfaces could be released persistently via a near-infrared laser-triggered manner. Interestingly, compared with colistin-loaded PDA NSs decorated sparsely with large silver nanoparticles (s-CPSs), the u-CPSs exhibited stronger antibacterial and antibiofilm effects. We have also demonstrated that the u-CPSs could disrupt the cell walls/ membranes of Gram-negative Escherichia coli bacteria and induce the generation of toxic reactive oxygen species within the bacteria. Collectively, the present work exemplifies the exquisite design and synthesis of PDA-based nanohybrids for achieving synergistic antibacterial and antibiofilm activities, which may promote the development of more powerful nanoagents to fight against bacterial infections.

Nanoradiosensitizers are promising agents for enhancing cancer radiotherapeutic efficiency. Although many attempts have been adopted to improve their radiation enhancement effect through regulation of their size, shape, and/or surface chemistry, few methods have achieved satisfactory radiotherapeutic outcomes. Herein, we propose a sequential drug treatment strategy through cell cycle regulation for achieving improved radiotherapeutic performance of the nanoradiosensitizers. Docetaxel (DTX), a clinically approved first-line drug in breast cancer treatment, is first used to affect the cell cycle distribution and arrest cells in the G2/M phase, which has been proven to be the most effective phase for endocytosis and the most radiosensitive phase for radiotherapy. The cells are then exposed to a commonly used nanoradiosensitizer, gold nanoparticles (GNPs), followed by X-ray irradiation. It is found that by arresting the cancer cells in G2/M phase via the DTX pretreatment, the cellular internalization of GNPs is significantly promoted, therefore enhancing the radiosensitivity of cancer cells. The sensitization enhancement ratio of this sequential DTX/GNP treatment reaches 1.91, which is significantly higher than that (1.29) of GNP treatment. Considering its low cost, simple design, and high feasibility, this sequential drug delivery strategy may hold great potential in radiotherapy.

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