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Conspectus Reactivity-based organic bioprobes have been increasingly designed and developed in the last couple of years to address important questions in numerous fields, particularly in biology and medicine. Contrary to the conventional lock-and-key bioprobes, which rely on molecular recognition to probe biological systems and impart sensing specificity, reactivity-based bioprobes capitalize on molecular reactivity for selective target detection. In fact, reactivity-based sensing exploits the intrinsic differences in chemical reactivity to differentiate various chemical species possessing similar size and shape in biological systems. This unique sensing mechanism has been effective for the detection of a wide range of chemical analytes in living cells, tissues, and animals, although bioprobes with additional functionalities are increasingly required in the quest to unravel and understand the complex biological systems. This is why the integration of diagnostic and therapeutic functions in one theranostic platform has become a continuous pursuit in the development of bioprobes in recent years. To this end, numerous design and synthetic approaches have been explored, notably that combining different organic materials with distinct functionalities into one integrated system, also known as “all-in-one” strategy. Nevertheless, the “all-in-one” strategy is prone to design complexity and unsatisfactory reproducibility. To minimize these undesirable hurdles, the deliberate design and engineering of simple organic molecules with multiple functionalities have been actively pursued, leading to the emergence of a unique approach known as “one-for-all” strategy. A prominent example of this approach leverages on fluorogens with aggregation-induced emission (AIE) characteristic. Through smart molecular engineering, we and other groups have recently shown that conventional organic AIE fluorogens can be specifically tailored to offer both imaging and therapeutic functionalities, such as photosensitizing ability to facilitate photodynamic therapy. The creation of this new class of versatile organic theranostic bioprobes with simultaneous imaging and therapeutic capabilities has further enabled image-guided chemotherapy and image-guided photodynamic therapy. Essentially, from this endeavor, replacing the fluorophores of conventional reactivity-based bioprobes with multifunctional molecules will yield reactivity-based organic theranostic bioprobes with enhanced capabilities and improved performance. In this Account, we summarize the latest advancement of reactivity-based theranostic bioprobes. To start with, we discuss the fundamental differences between conventional lock-and-key and reactivity-based sensing mechanisms, followed by general design routes of reactivity-based organic theranostic bioprobes. We then describe our efforts in recent years in formulating reactivity-based organic biosensing/imaging probes and multifunctional theranostic probes as well as in utilizing these bioprobes in detecting various chemical species in l...

The design of multifunctional drug delivery systems capable of simultaneous target detection, imaging, and therapeutics in live mammalian cells is critical for biomedical research. In this study, by using mesoporous silica nanoparticles (MSNs) chemically modified with a small-molecule dark quencher, followed by sequential drug encapsulation, MSN capping with a dye-labeled antisense oligonucleotide, and bioorthogonal surface modification with cell-penetrating poly(disulfide)s, the authors have successfully developed the first mesoporous silica nanoquencher (qMSN), characterized by high drug-loading and endocytosis-independent cell uptake, which is able to quantitatively image endogenous survivin mRNA and release the loaded drug in a manner that depends on the survivin expression level in tumor cells. The authors further show that this novel drug delivery system may be used to minimize potential cytotoxicity encountered by many existing small-molecule drugs in cancer therapy.

Photoluminescence quantum yield (PLQY) is one of the most important characteristics for organic luminescent materials. However, when carbazole prepared from the lab was compared to that from a commercial source, a remarkable change of PLQY was observed to vary from 37.1% to 69.8%. Taking 9-(4-bromo­benzyl)-9H-carbazole (CzBBr) as an example of carbazole derivatives, the PLQYs of CzBBr synthesized from different origins of carbazole were varied from 16.0% to 91.1%. Our studies demonstrated that efficient radiative transition pathways were activated for commercial carbazole based luminescence, leading to a large enhancement in PLQY with fluorescence (from 16.0% to 54.4%) and phosphorescence (from <1% to 36.7%) for CzBBr. These results suggest that the origin of carbazole plays a very important role in determining the optical properties of carbazole derivatives, alerting us to carefully revisit carbazole and its derivatives, especially those with record-high efficiency.

Doping has shown very promising potential in endowing room‐temperature phosphorescence (RTP) properties of organic phosphors with minimal effort. Here, a new isomer design and doping strategy is reported that is applicable to dibenzothiophene (DBT) and its derivatives. Three isomers are synthesized to study the dopant effect on enhancing RTP of DBT derivatives. It is found that isomer dopants bearing close resemblance to the host with matched highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels and small energy difference between singlet‐ and triplet‐excited states can yield efficient RTP for the doped system. Meanwhile, phosphorescence color from yellow to red is achieved by varying isomer dopants used for doping the DBT derivatives. This work represents an RTP enhancement strategy based on isomer design and doping to construct luminescent organic phosphors.