Simple design of fluorescein-based probe for rapid and in situ visual monitoring of histamine levels in food spoilage.

With the emergence of numerous food safety problems, rapid and accurate detection of histamine in food spoilage remains a challenge. To this end, we developed a simple design and easy synthesis of fluorescein-based probe FCHO to achieve specific and rapid (<1 s) quantitative detection of histamine through "imine formation" reaction. Significant enhanced fluorescence signal in response to histamine enabled our probe with high sensitivity as low as 51 nM. Utilizing the visualized fluorescence color changes of the probe as histamine increasing, we combined it with paper-based test chip to construct a color-resolved and highly selective recognition system. In addition, our proposed probe has been successfully used to visually imaging histamine changes in fish samples. Finally, for the first time, we have proved it possesses reliable ability to directly in situ imaging the distribution of histamine in whole spoiled fish. Thus, our strategy will provide great potential for monitoring food spoilage.

Covalent assembly-based two-photon fluorescent probes for in situ visualizing nitroreductase activities: From cancer cells to human cancer tissues.

Nitroreductase (NTR) is widely regarded as a biomarker whose enzymatic activity correlates with the degree of hypoxia in solid malignant tumors. Herein, we utilized 2-dimethylamino-7-hydroxynaphthalene as fluorophore linked diverse nitroaromatic groups to obtain four NTR-activatable two-photon fluorescent probes based on covalent assembly strategy. With the help of computer docking simulation and in vitro assay, the sulfonate-based probe XN3 was proved to be able to identify NTR activity with best performances in rapid response, outstanding specificity, and sensitivity in comparison with the other three probes. Furthermore, XN3 could detect the degree of hypoxia by monitoring NTR activity in kinds of cancer cells with remarkable signal-to-noise ratios. In cancer tissue sections of the breast and liver in mice, XN3 had the ability to differentiate between healthy and tumorous tissues, and possessed excellent fluorescence stability, high tissue penetration and low tissue autofluorescence. Finally, XN3 was successfully utilized for in situ visualizing NTR activities in human transverse colon and rectal cancer tissues, respectively. The findings suggested that XN3 could directly identify the boundary between cancer and normal tissues by monitoring NTR activities, which provides a new method for imaging diagnosis and intraoperative navigation of tumor tissue.

Homologous Tumor Cell-Derived Biomimetic Nano-Trojan Horse Integrating Chemotherapy with Genetherapy for Boosting Triple-Negative Breast Cancer Therapy.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that carries the worst prognosis and lacks specific therapeutic targets. To achieve accurate "cargos" delivery at the TNBC site, we herein constructed a novel biomimetic nano-Trojan horse integrating chemotherapy with gene therapy for boosting TNBC treatment. Briefly, we initially introduce the diselenide-bond-containing organosilica moieties into the framework of mesoporous silica nanoparticles (MONs), thereby conferring biodegradability to intratumoral redox conditions in the obtained MONSe. Subsequently, doxorubicin (Dox) and therapeutic miR-34a are loaded into MONSe, thus achieving the combination of chemotherapy and gene-therapy. After homologous tumor cell membrane coating, the ultimate homologous tumor cell-derived biomimetic nano-Trojan horse (namely, MONSe@Dox@miR-34a@CM) can selectively enter the tumor cells in a stealth-like fashion. Notably, such a nanoplatform not only synergistically eradicated the tumor but also inhibited the proliferation of breast cancer stem-like cells (BCSCs) in vitro and in vivo. With the integration of homologous tumor cell membrane-facilitated intratumoral accumulation, excellent biodegradability, and synergistic gene-chemotherapy, our biomimetic nanocarriers hold tremendous promise for the cure of TNBC in the future.

Stimuli-responsive biodegradable silica nanoparticles: From native structure designs to biological applications.

Due to their inherent advantages, silica nanoparticles (SiNPs) have greatly potential applications as bioactive materials in biosensors/biomedicine. However, the long-term and nonspecific accumulation in healthy tissues may give rise to toxicity, thereby impeding their widespread clinical application. Hence, it is imperative and noteworthy to develop biodegradable and clearable SiNPs for biomedical purposes. Recently, the design of multi-stimuli responsive SiNPs to improve degradation efficiency under specific pathological conditions has increased their clinical trial potential as theranostic nanoplatform. This review comprehensively summaries the rational design and recent progress of biodegradable SiNPs under various internal and external stimuli for rapid in vivo degradation and clearance. In addition, the factors that affect the biodegradation of SiNPs are also discussed. We believe that this systematic review will offer profound stimulus and timely guide for further research in the field of SiNP-based nanosensors/nanomedicine.

Colorimetric visualization of histamine secreted by basophils based on DSP-functionalized gold nanoparticles.

Histamine released by activated basophils has become an important biomarker and therapeutic target in the development of allergic diseases. To date, several gold nanoparticle (AuNP)-based nanosensors have been reported for histamine detection in foods. However, rapid, highly sensitive and direct detection of histamine in allergic diseases is still lacking due to the complexity of the physical environment. Herein, we developed a novel nanosensor for colorimetric visualization of histamine in activated basophils by simply coupling dithiobis(succinimidylpropionate) (DSP) on the surface of AuNPs (DSP-AuNPs). The DSP moiety serves as a linker and can react with the aliphatic amino group of histamine, and the imidazole ring of histamine can selectively bind with Au by means of p-p conjugation, thus inducing the aggregation of AuNPs. In this study, we experimentally proved that DSP-AuNPs showed good sensitivity and selectivity to histamine among various amino acids, including histidine. Additionally, this nanosensor displayed a rapid response to histamine with a linear range of 0.8-2.5 µM, and the limit of detection (LOD) was 0.014 µM, which is a relatively low LOD in comparison with those of other AuNP-based nanosensors. Finally, DSP-AuNPs are used, for the first time, to successfully detect endogenous histamine changes in activated basophils. Therefore, our work may provide a promising strategy to monitor histamine levels in the basophil activation test.