Liang Gong

Achieving highly sensitive and precise detection and imaging of cancer cells within the body is crucial for providing pathological information support in disease diagnosis and treatment. However, due to the existence of factors such as non-specific activation in local areas, membrane barriers, and the complexity of the intracellular environment, the tumor imaging strategies based on a single biomarker are subject to interference from false positive signals, which restricts the precise distinction between tumor tissues and normal tissues. To address these problems, we employ an “AND” logic gating mechanism, integrating the high ATP content and high expression of FEN1 within cancer cells as multiple targets for coordinated responses, to construct an ATP-mediated strategy for activating a self-assembled nanoprobe (named AFG probe) with FEN1-responsive properties for selective recognition and precise imaging of cancer cells. The design leverages the conformational adaptability of ATP aptamers to hybridize and assemble DNA nanoprobes with tunable sizes through the adjustment of the monomer. Once internalized within cancer cells, the high ATP concentrations present trigger a conformational shift of the aptamer, leading to the formation of substrate structures that can be specifically recognized by the intracellular target FEN1. These substrates undergo cleavage under the enzymatic action of FEN1, which leads to the dissociation of the nanoprobe and generates fluorescence signals. The results demonstrate that the programmable AFG probe exhibits high sensitivity, specificity, and stability. Furthermore, we verified the ability of the AFG probe to dynamically monitor the changes of FEN1 within cancer cells, and systematically evaluated its imaging performance in breast cancer cells, lung cancer cells, normal cells, lung cancer tissues and normal tissues, as well as in live mice. All these findings indicate that this probe, by utilizing the high concentration of ATP and high expression of FEN1 in cancer cells, can effectively distinguish tumor tissues from normal tissues. This strategy provides a idea for precise imaging of FEN1-related tumors and offers technical support for overcoming the problem of false positives based on a single biomarker.

Bilayer hydrogel actuators, consisting of an actuating layer and a functional layer, show broad applications in areas such as soft robotics, artificial muscles, drug delivery and tissue engineering due to their inherent flexibility and responses to stimuli. However, to achieve the compatibility of good stimulus responses and high mechanical properties of bilayer hydrogel actuators is still a challenge. Herein, based on the double-network strategy and using the synchronous ultraviolet (UV) polymerization method, an upper critical solution temperature (UCST)-type bilayer hydrogel actuator was prepared, which consisted of a poly(acrylamide-co-acrylic acid)[MC] actuating layer and an agar/poly(N-hydroxyethyl acrylamide-co-methacrylic acid)[AHA] functional layer. The results showed that the tensile stress/strain of the bilayer hydrogel actuator was 1161.21 KPa/222.07%. In addition, the UCST of bilayer hydrogels was ~35 °C, allowing the bilayer hydrogel actuator to be curled into an “◎” shape, which could be unfolded when the temperature was 65 °C, but not at a temperature of 5 °C. Furthermore, hydrogel actuators of three different shapes were designed, namely “butterfly”, “cross” and “circle”, all of which demonstrated good actuating performances, showing the programmable potential of bilayer hydrogels. Overall, the bilayer hydrogels prepared using double-network and synchronous UV polymerization strategies realized the combination of high mechanical properties with an efficient temperature actuation, which provides a new method for the development of bilayer hydrogel actuators.

Disease signaling molecules and biomarkers are important in biosensing and biomedicine, and their ultra‐sensitive detection and imaging are critical in medical diagnosis. However, most biomarkers have low levels of expression in cells and are easily degraded; therefore, they cannot be accurately detected in real time by conventional amplification methods, which are typically confined to cell lysates. To achieve highly sensitive detection of intracellular low‐abundance molecules, extensive efforts have been devoted to the development of in situ signal amplification techniques. This review tracks the development of recent advances in in situ signal amplification strategies, and systematically summarizes the advantages and disadvantages of enzymatic and non‐enzymatic amplification techniques for detecting and tracing intracellular targets. Further, perspectives, challenges, and opportunities for intracellular signal amplification are discussed to promote its adoption for in situ signal amplification in clinical settings and to provide new insights into signaling molecules and biomarkers in cellular functions and associated diseases.

Electronic skin (e‐skin) is widely studied for its ability to detect physiological information and provide feedback through electrical signals. Biocompatible stimulus‐responsive DNA‐based hydrogels exhibit high sensitivity, which makes them outstanding candidates for biomedical applications. However, several disadvantages, such as weak mechanical properties, expensive manufacturing costs, cumbersome double chain design, and difficulty obtaining bulk size, seriously limit their practical application. Based on the double network (DN) strategy, a universal, low‐cost, and high‐toughness deoxyribonucleic acid/poly(N‐hydroxyethyl acrylamide) (DNA/pHEAA) DN hydrogel is designed. The transparent hydrogel shows tensile stress/strain of 0.96 ± 0.043 MPa/2537.55 ± 23.24%, rapid self‐recovery ability (peak stress/energy dissipation recovery rate of 99.72%/95.38% after 30 s resting), excellent fatigue resistance (peak stress/energy dissipation retention rate of 91.08%/81.05% after 100 loading‐unloading cycles with strain of 50%), reversible adhesive ability (≈45 KPa), and good biocompatibility. Thus, the DNA/pHEAA DN hydrogel can be used as an e‐skin. Sensing signals are displayed on a smartphone as images sent through wireless technology; the images change with the collected signals, achieving motion detection. The universal and low‐cost design of stimulus‐responsive DNA‐based hydrogels with high toughness, excellent self‐recovery, and anti‐fatigue performance is expected to promote their application in the biomedical field.

Recently, hydrogel flexible sensors have attracted wide attention in the field of wearable electronic devices. However, they need an external solid-state power supply to output stable signals. The huge modulus difference between solid-state power supplies and hydrogel flexible sensors is not conducive to the integration, portability, and application of hydrogel flexible sensors. Therefore, it is necessary to design power supplies with a similar modulus to those of flexible sensors and assemble them with flexible sensors to develop self-powered flexible sensing systems, which is important to facilitate the integration, portability, and application of flexible sensors. In this work, polyvinyl alcohol (PVA), sodium chloride (NaCl), and N-hydroxyethyl acrylamide (HEAA) were used to synthesize a fully physically crosslinked double network hydrogel (PNH DN hydrogel) with excellent mechanical performance (tensile stress/strain of 3.76 MPa/872.15%), high ionic conductivity (1.3 S m⁻¹), and rapid self-recovery (energy dissipation/peak stress recovery efficiency of 57.08%/99.06% after a rest time of 10 min). Based on PNH DN hydrogels, a hydrogel strain sensor and a flexible solid-state supercapacitor were prepared, respectively. The hydrogel strain sensor based on the PNH DN hydrogel showed good sensitivity (gauge factor = 1.74), a wide detection range (0–735%), and a negligible response delay time (0.06 s), which are helpful for timely and reliable detection of various mechanical deformations. Meanwhile, the supercapacitor based on the PNH DN hydrogel exhibited an areal capacitance of 2.9 mF cm⁻², a high cycle stability (areal capacitance retention rate of 85.71% after 2000 galvanostatic charge–discharge cycles at a current density of 0.5 mA cm⁻²), and mechanical stability (cyclic voltammetry curves were almost overlapped under 0°, 45°, 90°, 135°, and 180° bending). Finally, the hydrogel strain sensor and supercapacitor were integrated into a self-powered flexible sensing system, which could stably and effectively detect human motions, such as finger bending, neck bending, and frowning. Overall, this work provides a new idea to improve the integration, portability, and application of hydrogel flexible sensors and can broaden the application of hydrogels in the field of new energy.

Hydrogels, as classic soft materials, are important materials for tissue engineering and biosensing with unique properties, such as good biocompatibility, high stretchability, strong adhesion, excellent self-healing, and self-recovery. Conductive hydrogels possess the additional property of conductivity, which endows them with advanced applications in actuating devices, biomedicine, and sensing. In this review, we provide an overview of the recent development of conductive hydrogels in the field of strain sensors, with particular focus on the types of conductive fillers, including ionic conductors, conducting nanomaterials, and conductive polymers. The synthetic methods of such conductive hydrogel materials and their physical and chemical properties are highlighted. At last, challenges and future perspectives of conductive hydrogels applied in flexible strain sensors are discussed.

DNAzymes, screened through in vitro selection, have shown great promise as molecular tools in the design of biosensors and nanodevices. The catalytic activities of DNAzymes depend specifically on cofactors and show multiple enzymatic turnover properties, which make DNAzymes both versatile recognition elements and outstanding signal amplifiers. Combining nanomaterials with unique optical, magnetic and electronic properties, DNAzymes may yield novel fluorescent, colorimetric, surface-enhanced Raman scattering (SERS), electrochemical and chemiluminescent biosensors. Moreover, some DNAzymes have been utilized as functional components to perform arithmetic operations or as “walkers” to move along DNA tracks. DNAzymes can also function as promising therapeutics, when designed to complement target mRNAs or viral RNAs, and consequently lead to down-regulation of protein expression. This feature article focuses on the most significant achievements in using DNAzymes as recognition elements and signal amplifiers for biosensors, and highlights the applications of DNAzymes in logic gates, DNA walkers and nanotherapeutics.