Fluorescent nanosensor-based tumor imaging holds great promise in cancer diagnosis and treatment assistance, yet the signal contrast is heavily hampered by the unspecific/unwanted activation at microscopic regions with a highly restricted local abundance of biomarkers. Herein, we developed an activation boosting strategy by the integration and manipulation of dual-factor coactivation of sensing and lysosome escape facilitated the rise of cytosolic biomarker accessibility. By employing hybrid DNA probes on gold nanoquenchers, ATP sensing initiated conformation switch of the corresponding aptamer units triggered the exposure of a hidden toehold in a loop structure. Sequentially, miRNA-21 sensing was triggered by toehold-mediated strand displacement and detachment of the binding complexes. The application of lysosomotropic agent chloroquine at optimized time interval facilitated the release of nanosensors into the cytosol and a ∼10.5-fold increment of intracellular fluorescence in vitro, while coactivation improved the cancer-to-normal cell signal ratio by ∼5.9 times. The synergy effects led to a high tumor-to-normal tissue ratio value of ∼7.9 in the in vivo imaging results. This strategy establishes a new paradigm of fluorescent nanosensors for selective and specific tumor imaging.

MiRNA-targeted therapy holds great promise for precision cancer therapy. It is important to investigate the effect of changes in miRNA expression on apoptosis in order to evaluate miRNA-targeted therapy and achieve personalized therapy. In this study, we designed a dual-color fluorescent nanosensor consisting of grapheme oxide modified with a molecular beacon and peptide. The nanosensor can simultaneously detect and image miRNA-221 and apoptotic protein caspase-3 in living cells. Intracellular experiments showed that the nanosensor could be successfully applied for in situ monitoring of the effect of miRNA-221 expression changes on apoptosis by dual-color imaging. The current strategy could provide new avenues for investigating the feasibility of miRNA-targeted therapy, screening new anti-cancer drugs targeting miRNA and developing personalized treatment plans.

Instrument-free, portable, and direct read-out mini-devices have wider application prospects in various fields, especially for real-time/on-site sensing. Herein, combined with a paper strip, a smartphone sensing platform integrated with a UV lamp and dark cavity by 3D-printing technology has been developed for the rapid, sensitive, instrument-free, and visual quantitative analysis in real-time/on-site conditions. The platform proved the feasibility for visual quantitative detection of pesticide via a fluorescence \"on-off-on\" response with a single dual-emissive ratiometric paper strip. Red-emitting CdTe quantum dots (rQDs) were embedded into the silica nanoparticles (SiO2 NPs) as an internal reference, while blue-emitting carbon dots (bCDs) as a signal report unit were covalently linked to the outer surface of SiO2 NPs. The blue fluorescence could be quenched by gold nanoparticles (Au NPs) and then recovered with pesticide. The red (R), green (G), and blue (B) channel values of the generated images were determined by a color recognizer application (APP) installed in the smartphone, and the R/B values could be used for pesticide quantification with a sensitive detection limit (LOD) of 59 nM. The smartphone sensing platform based on 3D printing might provide a general strategy for visual quantitative detection in a variety of fields including environments, diagnosis, and safety monitoring.

In this work, it is presented for the first time that nitrogen and chlorine co-doped carbon nanodots (N,Cl-CDs) were synthesized by simply mixing glucose, concentrated hydrochloric acid (HCl), and 1,2-ethylenediamine (EDA). No external heat was employed; the neutralization reaction served as the heat source. The glucose served as the carbon source while EDA and HCl were the N and Cl dopants, respectively. The fluorescence of N,Cl-CDs was adequately quenched by hexavalent chromium Cr(VI) based on a combination of dynamic quenching and inner filter effect (IFE). Accordingly, an efficient N,Cl-CDs-based fluorescence probe was established for sensitive and selective detection of Cr(VI). The proposed fluorescence sensor provides a linear recognition range for Cr(VI) determination from 3 to 40 µM with a limit of detection (LOD) of 0.28 µM (14.6 µg/L). The proposed fluorescence method was successfully utilized to detect Cr(VI) in different water samples with satisfactory results. The spike recoveries vary from 97.01% to 103.89% with relative standard deviations (RSDs) of less than 0.82%. This work highlights the development of a simple, ultrafast, and energy-saving one-step synthetic route to fabricate N,Cl-CDs for highly selective and sensitive detection of Cr(VI) in real water samples. It is anticipated that the proposed fluorescence method could be further explored and widely used for Cr(VI) detection in the environmental industry.

Trypsin and its inhibitors are relevant to many physiological processes and diseases. In this study, a nanosensor capable of detecting trypsin and its inhibitors was designed based on the fluorescence resonance energy transfer (FRET) between upconversion nanoparticle (UCNP) and gold nanoparticle (AuNP). UCNP and AuNP were linked by a trypsin-sensitive peptide DDDDARC, forming the non-fluorescent UCNP-peptide-AuNP nanosensor. In the presence of trypsin, the peptide was cleaved and the quenched fluorescence was restored; in the presence of trypsin inhibitors, the recovery of the fluorescence was decreased. The nanosensor showed a superb sensitivity and selectivity for trypsin and its inhibitors, with a detection limit of 4.15ngmL-1 for trypsin. UCNP-peptide-AuNP could eliminate the interference of background fluorescence and avoid the light toxicity, and potentially be used to diagnose trypsin-related diseases or screen trypsin inhibitors.