Compared with conventional tumor photothermal therapy (PTT), mildtemperature PTT brings less damage to normal tissues, but also tumor thermoresistance, introduced by the overexpressed heat shock protein (HSP). A high dose of HSP inhibitor during mild-temperature PTT might lead to toxic side effects. Glucose oxidase (GOx) consumes glucose, leading to adenosine triphosphate supply restriction and consequent HSP inhibition. Therefore, a combinational use of an HSP inhibitor and GOx not only enhances mildtemperature PTT but also minimizes the toxicity of the inhibitor. However, a GOx and HSP inhibitor-encapsulating nanostructure, designed for enhancing its mild-temperature tumor PTT efficiency, has not been reported. Thermosensitive GOx/indocyanine green/gambogic acid (GA) liposomes (GOIGLs) are reported to enhance the efficiency of mild-temperature PTT of tumors via synergistic inhibition of tumor HSP by the released GA and GOx, together with another enzyme-enhanced phototherapy effect. In vitro and in vivo results indicate that this strategy of tumor starvation and phototherapy significantly enhances mild-temperature tumor PTT efficiency. This strategy could inspire people to design more delicate platforms combining mildtemperature PTT with other therapeutic methods for more efficient cancer treatment.

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.

The therapeutic performance of cancer radiotherapy is often limited by the overexpression of glutathione (GSH) in tumors and low radiation sensitivity of cancerous cells. To address these issues, the facilely prepared histidine-capped gold nanoclusters (Au NCs@His) were adopted as a radiosensitizer with a high sensitization enhancement ratio of ∼1.54. On one hand, Au NCs@His can inherit the local radiation enhancement property of gold-based materials (external regulation); on the other hand, Au NCs@His can decrease the intracellular GSH level, thus preventing the generated reactive oxygen species (ROS) from being consumed by GSH, and arrest the cells at the radiosensitive G2/M phase (internal regulation).

Theranostic nanoparticles (NPs) capable of mitochondrial targeting/imaging, cancer/normal cell differentiation, early stage cancer diagnosis, and mitochondria-based photothermal therapy (PTT) were developed. The NPs were fabricated by physical encapsulation of nearinfrared (NIR) heptamethine cyanine dye me-IR825 into the inner core of the micelle-forming copolymer Pluronic F127 (PF127). The PF127/me-IR825 NPs exhibited two fluorescence emissions at ∼610 nm (excited by 550 nm) and 845 nm (excited by 780 nm). The former was used for in vitro mitochondrial fluorescence imaging, cancer/normal cell differentiation, and early stage cancer detection with high fluorescence contrast. The latter was used for in vivo NIR fluorescence imaging. Besides, the NPs could also be used for in vivo photoacoustic imaging under 808 nm excitation. After irradiation by an 808 nm laser at an elevated power density, the NPs achieved excellent photothermal tumor ablation both in vitro and in vivo. Furthermore, me-IR825 inside the inner core of PF127/ me-IR825 NPs could be degraded into biocompatible products after PTT treatment, which guaranteed the post-treatment biosafety of the NPs. Benefiting from their simple preparation, good colloidal dispersibility/stability, excellent cancer/normal cell differentiation ability, and superb in vivo dual-modal imaging-guided therapeutic outcome, the PF127/me-IR825 NPs may be used as a theranostic nanoplatform for applications in the biomedical field.

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.

Many noble metal-based nanoparticles have emerged for applications in cancer radiotherapy in recent years, but few investigations have been carried out for palladium nanoparticles. Herein, palladium nanosheets (Pd NSs), which possess a sheetlike morphology with a diameter of ∼14 nm and a thickness of ∼2 nm, were utilized as a sensitizer to improve the performance of radiotherapy. It was found that Pd NSs alone did not decrease the cell viability after treatment for as long as 130 h, suggesting the excellent cytocompatibility of the nanoagents. However, the viability of cancer cells treated with X-ray irradiation became lower, and the viability became even lower if the cells were co-treated with X-ray and Pd NSs, indicating the radiosensitization effect of Pd NSs. Additionally, compared with X-ray irradiation, the combined treatment of Pd NSs and X-ray irradiation induced the generation of more DNA double-stranded breaks and reactive oxygen species within cancer cells, which eventually caused elevated cell apoptosis. Moreover, in vivo experiments also verified the radiosensitization effect and the favorable biocompatibility of Pd NSs, indicating their potential for acquiring satisfactory in vivo radiotherapeutic effect at lower X-ray doses. It is believed that the present research will open new avenues for the application of noble metal-based nanoparticles in radiosensitization.

Purpose: This study assessed the clinical significance of c-myc gene copy number gain detected by fluorescence in situ hybridization (FISH) in the prediction of cervical intraepithelial neoplasia (CIN) progression. Methods: We retrospectively investigated 140 Thinprep cytologic test (TCT) specimens that were histopathologically diagnosed with various stages of cervical neoplasia or malignancy. The specimens were subjected to TCT, human papillomavirus (HPV) testing, and FISH analysis with a c-myc-specific probe. The diagnostic reliability of these methods in determining progression was assessed according to sensitivity, specificity, and κ coefficients. Results: The gene copy number gain of c-myc was significantly higher in the cervical lesion of advanced histologic grade (p < 0.001). For CIN2+ lesions, the sensitivities of TCT, HPV DNA testing, and FISH analysis were 72.3, 92.1, and 64.5%, respectively; the specificities were 81.3, 57.8, and 93.8%, respectively (p < 0.001). The κ coefficients between the c-myc gene test and either the TCT or the HPV DNA test were 0.538 and 0.399, respectively (p < 0.001). Conclusions: FISH analysis of the c-myc oncogene could be a useful adjunct screening method for the early diagnosis of high-grade cervical lesions. Moreover, c-myc may be a new molecular biomarker for the early diagnosis of cervical lesion progression.