Theranostic systems by integrating the tumor imaging and tumor therapeutic capabilities into one platform have attracted numerous attentions from worldwide researchers. Despite the great developments, their clinical application is still in the nascent stage, owing to the unsatisfied imaging quality and limited therapeutic efficacy. Fortunately, the emerging of aggregation‐induced emission (AIE) molecules with unique fluorescence property offers an opportunity to solve the imaging problem. Besides, further utilizing the tumor microenvironments and external triggers to design the stimuli‐responsive imaging‐guided therapy could enhance the therapeutic efficacy and reduce the side effects. In this review, the advancements in stimuli‐responsive theranostic systems with AIE characteristics are summarized. Theranostic systems are first classified according to their treatment modes, and then subdivided based on various stimuli, including pH, redox, enzyme, and light. In each section, the design strategies and application examples are introduced. At last, the current state of the art, limitations, as well as prospects are also discussed.

By maintaining the telomere lengths, telomerase can make the tumor cells avoid the apoptosis, thus, achieving the cell immortalization. In the past, a series of telomerase detection systems have been developed through utilizing the unique characteristic of telomerase extended primer. However, fluctuation of telomerase activity, along with the cell cycle progression, leads to ambiguous detection results. Here, we reported a dual signal output detection strategy based on cell-cycle synchronization for precisely detecting telomerase activities by using a new AIEgen probe SSNB. Experimental and simulating calculation results demonstrated that positively charged SSNB could interact with DNA through the electrostatic interaction and π−π interaction, as well as the hydrogen bonds. The aggregation of SSNB caused by the extended template strand primer (TP) could be observed in tumor cells, thus, indicating the telomerase activity in various cell lines. Furthermore, after cell cycle synchronization, it was found that the telomerase activity in the S phase was the highest, no matter from the fluorescence intensity or the ROS generation situation. Dual signal outputs of SSNB verified the significance and necessity of cell-cycle synchronization detection for telomerase activity. This strategy could open a new window for the biotargets of which activity is variational in time dimension.

Functional probes not only at the inner wall but also at the outer surface of nanochannel systems could be used for the recognition and detection of biotargets. Despite the advancements, the current detection mechanisms are still mainly based on the surface charge variation. We proposed a strategy of using the variation of wettability on the outer surface of nanochannels for detecting a tumor marker, herein, exemplifying matrix metalloproteinase-2 (MMP-2). The outer surface of the nanochannels were modified with amphipathic peptide probe consisting of hydrophilic unit (CRRRR), MMP-2 cleavage unit (PLGLAG), and hydrophobic unit (Fn). After recognition of MMP-2, due to the release of hydrophobic unit, the hydrophilicity of the outer surface was expected to increase, thus leading to the increase of ion current. Furthermore, the number (n) of phenylalanine (F) in the hydrophobic unit was modulated from 2, 4, to 6. By lengthening the hydrophobic unit, the limit of detection for MMP-2 detection could reach 1 ng/ mL (when n = 6) and improve by 50-fold (to n = 2). This nanochannel system was utilized to successfully detect the MMP-2 secreted from cells and demonstrated that the expression of MMP-2 was related to the cell cycle and exhibited the highest level in G1/S phase. This study proved that in addition to the surface charge, wettability regulation could also be utilized as a variation factor to broaden the design strategy of a probe on OS to achieve the detection of biotargets.

Precisely analyzing the target materials in living cells can reveal the essence and mystery of life at a deeper level, which will provide reliable theoretical basis for the occurrence, development, treatment and prognosis of major diseases. However, because living cells are in the dynamic process of metabolism, there are several challenges existed in accurate analysis, including subcellular compartment heterogeneity, plasma membrane interface barrier, and cell cycle regulation. In this regard, our group has designed and synthesized a series of multifunctional aggregates by mainly integrating the peptide elements, nucleic acid elements and aggregation elements to overcome the barriers. This article summarizes the latest developments of multifunctional aggregates for precise cell analysis by our group, and systematically introduces them according to different design concepts and targeting dimensions, such as space, efficiency as well as time. We hope this work could contribute to analyzing the biomarkers in cells through constructing the multifunctional aggregates, understanding the operation mechanism of cells, finally inspiring technology breakthroughs in biomedical fields.

Utilizing ionic current and fluorescent dual-signal-output nanochannels to achieve the detection of specific target species has received much attention. The introduction of an optical signal could not only improve the selectivity of the detection systems, but also make it possible to observe the reduction of the ionic current that originated from stimulus-triggered nanochannel changes. However, the resolution of an optical signal can only verify issues of the presence or absence and cannot precisely analyze the detailed chemical structural changes within nanochannels. Here, we employed a biocompatible condensation reaction between 2cyanobenzothiazole (CBT) and D-cysteine, and synthesized molecules PCTC that can be polymerized by cutting off short peptide sequences in the presence of furin to realize the detection of furin with multiple signal outputs. Through the introduction of a UV light-sensitive DNA sequence to the capture probes (CPs) inside the nanochannels, the blocking of the nanochannels can be confirmed to the formed oligomers by mass spectrometry analysis.

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Comprehensive Summary Cancers and chronic diseases have always been global health problems. The occurrence and development of such diseases are closely related to the abnormalities of proteins, nucleic acids, ions or small molecules in the body. Nowadays, nanopores/nanochannels have emerged as a powerful platform for detecting these biomolecules based on the electrical signal variation caused by biomolecules passing. However, detection relied on the electrical signal easily suffered from the clogging defects, low throughput, and strong background signals. Fortunately, the emergence of designing nanopores/nanochannels based on electrical and optical dual signal response has brought innovative impetus to biological detection, which can also identify the chemical compositions and conformations of the biomolecules. In this review, we summarize the reasonable preparation of nanopores/nanochannels with electrical and optical dual signal response and their application in biological detection. According to different biomolecules, we divide the targets into four types, including nucleic acids, small molecules, ions and proteins. In each section, the design of representative examples and the principle of dual signal generation are introduced and discussed. Finally, the prospects and challenges of nanopores/nanochannels based on electrical and optical dual signal response are also discussed.