Electrochemical and photoelectrochemical detection techniques have been widely applied in fields such as bioanalysis, environmental monitoring, and food safety due to their rapid response, operational simplicity, and high sensitivity. However, achieving highly selective recognition of target analytes in complex samples, enhancing sensitivity for trace analysis, and constructing stable electrode interfaces remain core challenges in this field. As the fifth-generation macrocyclic supramolecular hosts, pillar[n]arenes possess a unique pillar-shaped symmetrical structure, an electron-rich cavity, and readily functionalizable rims, enabling highly selective recognition of guest molecules through multiple non-covalent interactions. This provides new insights into addressing the above-mentioned challenges. This Feature Article systematically reviews the research progress of pillar[n]arenes in the field of electrochemical and photoelectrochemical detection. The related research work is summarized from two dimensions: first, the construction strategies for different types of pillar[n]arene-based electrode modification materials, including pure pillar[n]arene self-assembled materials, pillar[n]arene-metal nanocomposites, pillar[n]arene-inorganic nonmetallic nanomaterials, pillar[n]arene-metal/nonmetal hybrid nanomaterials, and cooperatively assembled materials based on two distinct types of pillar[n]arenes. Second, the applications of these pillar[n]arene-functionalized electrodes in the detection of various classes of substances, including biomarkers and disease-related substances, neurotransmitters and psychoactive substances, environmental pollutants and toxins, small biomolecules and metabolites, as well as inorganic active species. Finally, future development directions for pillar[n]arene-based electrochemical sensors are discussed, aiming to provide a reference for research on the rational design and applications of high-performance supramolecular electrochemical sensors.

Hyperthermia can be integrated with tumor-killing chemotherapy, radiotherapy and immunotherapy to give rise to an anti-tumor response. To this end, a nano-delivery system is built, which can connect hyperthermia and immunotherapy. On this basis, the impact of such a combination on the immune function of dendritic cells (DCs) is explored. The core of this system is the photothermal material gold nanorod (GNR), and its surface is covered with a silica shell. Additionally, it also forms a hollow mesoporous structure using the thermal etching approach, followed by modification of targeted molecule folic acid (FA) on its surface, and eventually forms a hollow mesoporous silica gold nanorod (GNR@void@mSiO2) modified by FA. GNR@void@mSiO2-PEG-FA (GVS-FA) performs well in photothermal properties, drug carriage and release and tumor targeting performance. Furthermore, the thermotherapy of tumor cells through in vitro NIR irradiation can directly kill tumor cells by inhibiting proliferation and inducing apoptosis. GVS-FA loaded with imiquimod (R837) can be used as a adjuvant to enhance the immune function of DCs through hyperthermia.

The lack of effective oral drug delivery systems to treat gastric ulcer is an urgent challenge in clinical practice. Herein, a gastric acid pH-responsive hydrogel of curcumin/sodium alginate/polyaspartic acid@CaCO3 (Cur/SA/PC) was developed for sustained release of Cur, exerting effective protection and treatment of gastric ulcers. The in vitro gelatinization properties and the corresponding gel characteristics of the SA/PC delivery system demonstrated the successful construction of the in situ hydrogel with uniform strength. The cellular uptake illustrated the successful uptake and sustained release of Cur. Besides, Cur effectively inhibited NLRP3-mediated pyroptosis both in vitro and in vivo, exhibited an excellent pro-healing effect by regulating the PI3K/Akt signaling pathway, and alleviated acetic acid-induced chronic gastric injury in rats. Moreover, the relative bioavailability of Cur in the SA/PC hydrogel could effectively increase in the pharmacokinetic study. Importantly, the protective barrier formed by the SA/PC hydrogel could effectively protect against alcohol-induced acute gastric ulcers in rats. Overall, the designed SA/PC oral delivery system is a promising strategy to overcome gastric barriers for oral drug delivery.

Reversing hypoxia-mediated multidrug resistance (MDR) presents a unique challenge in clinical chemotherapy. Here, a sequential dual delivery system composited with Cyclooxygenase-2 siRNA (siCOX-2) in poly-d-arginine (9R)/2-deoxyglucose (DG)-loaded gold nanostar (GNS) (siCOX-2@RDG) and paclitaxel (PTX)-loaded thermosensitive liposome (PTSL) was proposed to conquer the hypoxia-mediated MDR in tumors. As a result, the prepared siCOX-2@RDG exhibited a starlike morphology with a uniform particle size of 194.36 ± 1.44 nm and a ζ-potential of -11.83 ± 2.01 mV. In vitro, PTSL displayed expected thermal-responsive release properties. As expected, siCOX-2@RDG displayed exceptional DG-mediated hypoxia-targeting capability both in vitro and in vivo and downregulated the expression of COX-2 successfully. Meanwhile, GNS-triggered hyperthermia elevated the cellular uptake of PTSL in PTX-resistant HepG2(HepG2/PTX) cells in vitro and enhanced the permeability of tumor tissues, thus elevating the valid retention of PTX into solid tumors. Finally, we demonstrated that the sequential dual systems composed of siCOX-2@RDG and PTSL could reverse hypoxia-mediated MDR and exhibit excellent synergistic antitumor effects both in vitro and in vivo, prolonging the survival of tumor-bearing mice. The devised sequential dual systems, composed of two independent nanosystems, have a promising potential to overcome hypoxia-mediated MDR in clinical practice.

Toehold exchange spherical nucleic acids (TESNA) modulated on molybdenum disulfide (MoS2) acanthospheres were proposed for the discrimination of single nucleotide variants (SNVs). We rationally optimized the probe by making a trade-off between the discrimination factor (DF) and hybridization ratio (χ). The TESNA platform can distinguish SNVs with significantly improved sensitivity and specificity.

A DNA framework assembled split G4 nanodevice was fabricated to realize microRNA imaging in living HeLa cells. After hybridization with the target, the separated G4 segments underwent structural transformations, which could initiate fluorescence resonance energy transfer (FRET) processes. Our design may pave a novel way to facilitate applications of the G4 motif.

The fabrication of photosensitive interface and molecular recognition layer at the biosensing surface are of vital importance in photoelectrochemical (PEC) biosensor construction. Developing facial methods with favorable biomolecule immobilization as well as excellent photoelectric activity still need to be explored. In this work, by integration of the merits of tungsten oxide (WO3) semiconductor nanomaterial and polydopamine (PDA) polymer, a novel biofunctional PDA/WO3 nanocomposites (PDA/WO3 NCs) modified ITO hierarchical architecture was fabricated by simple thermal annealing and self-polymerization methods. The proposed PEC biosensor platform based on PDA/WO3/ITO not only have preponderances in simple preparation, but also possesses excellent PEC activity, high specific surface area and good microenvironment for biomolecule immobilization. Utilizing CYFRA 21-1 as a model target, label-free PEC immunosensor was developed successfully, which exhibited great sensitivity and broad dynamic range with four orders of magnitude (10 pg mL(-1) to 100 ng mL(-1)), and the limit of detection was as low as 2.5 pg mL(-1). Moreover, owing to the great sensitivity and selectivity of the proposed platform, this convenient sensor also performed well in real serum sample analysis. It is worth noting that our work not only helps in gaining a better understanding of the applicability of the PEC properties of PDA/WO3 NCs, but also sheds novel light on the design and development of PEC biosensing platform based on PDA/WO3 NCs.

A novel approach to program target-responsive devices by incorporating the split G4 motifs in a DNA nanocage has been developed. The rigid prism outcompetes the flexible one in reaction kinetics and signal/background ratios, which can be easily internalized by cells and successfully applied in microRNA imaging in live cells.

Recent decades have witnessed the revolutionary development of cancer immunotherapies, which boost cancer-specific immune responses for long-term tumor regression. However, immunotherapy still has limitations, including off-target side effects, long processing times and limited patient responses. These disadvantages of current immunotherapy are being addressed by improving our understanding of the immune system, as well as by establishing combinational approaches. Advanced biomaterials and gene delivery systems overcome some of these delivery issues, harnessing adverse effects and amplifying immunomodulatory effects, and are superior to standard formulations with respect to eliciting antitumor immunity. Nucleic acid-based nanostructures have diverse functions, ranging from gene expression and gene regulation to pro-inflammatory effects, as well as the ability to specifically bind different molecules. A brief overview is provided of the recent advances in the non-viral gene delivery methods that are being used to activate cancer-specific immune responses. Furthermore, the tumor microenvironment-responsive synergistic strategies that modulate the immune response by targeting various signaling pathways are discussed. Nanoparticle-based non-viral gene delivery strategies have great potential to be implemented in the clinic for cancer immunotherapy.

We propose a dynamic nanodevice based on a split G-quadruplex (G4). By splitting it apart, we can successfully decouple the G-tetrad formation from external stimuli, greatly expanding the stimulus for G4 based devices. Taking advantage of the rigid force from a DNA duplex, the nanodevice can be switched reversibly through the conformational transformation.