Planar donor and acceptor (D–A) conjugated structures are generally believed to be the standard for architecting highly efficient photothermal theranostic agents, in order to restrict intramolecular motions in aggregates (nanoparticles). However, other channels of extra nonradiative decay may be blocked. Now this challenge is addressed by proposing an “abnormal” strategy based on molecular motion in aggregates. Molecular rotors and bulky alkyl chains are grafted to the central D–A core to lower intermolecular interaction. The enhanced molecular motion favors the formation of a dark twisted intramolecular charge transfer state, whose nonradiative decay enhances the photothermal properties. Result shows that small-molecule NIRb14 with long alkyl chains branched at the second carbon exhibits enhanced photothermal properties compared with NIRb6, with short branched chains, and much higher than NIR6, with short linear chains, and the commercial gold nanorods. Both in vitro and in vivo experiments demonstrate that NIRb14 nanoparticles can be used as nanoagents for photoacoustic imaging-guided photothermal therapy. Moreover, charge reversal poly­(β-amino ester) makes NIRb14 specifically accumulate at tumor sites. This study thus provides an excited molecular motion approach toward efficient phototheranostic agents.

Semiconducting polymer nanoparticles (SPNs) emitting in the second near-infrared window (NIR-II, 1000− 1700 nm) are promising materials for deep-tissue optical imaging in mammals, but the brightness is far from satisfactory. Herein, we developed a molecular design strategy to boost the brightness of NIR-II SPNs: structure planarization and twisting. By integration of the strong absorption coefficient inherited from planar πconjugated units and high solid-state quantum yield (Φ PL ) from twisted motifs into one polymer, a rise in brightness was obtained. The resulting pNIR-4 with both twisted and planar structure displayed improved Φ PL and absorption when compared to the planar polymer pNIR-1 and the twisted polymer pNIR-2. Given the emission tail extending into the NIR-IIa region (1300−1400 nm) of the pNIR-4 nanoparticles, NIR-IIa fluorescence imaging of blood vessels with enhanced clarity was observed. Moreover, a pH-responsive poly(β-amino ester) made pNIR-4 specifically accumulate at tumor sites, allowing NIR-IIa fluorescence image-guided cancer precision resection. This study provides a molecular design strategy for developing highly bright fluorophores.

On the basis of the Jablonski diagram, the photophysical properties of optical agents are highly associated with biomedical function and efficacy. Herein, the focus is on organic/polymer optical agents and the recent progress in the main strategies for regulating their photophysical properties to achieve superior cancer diagnosis/phototheranostics applications are highlighted. Both the approaches of nanoengineering and molecular design, which can lead to optimized effectiveness of required biomedical function, are discussed.

Phototheranostics that concurrently and complementarily integrate real‐time diagnosis and in situ therapeutic capabilities in one platform has become the advancing edge of precision medicine. Organic agents possess the merits of facile preparation, high purity, tunable photophysical property, good biocompatibility, and potential biodegradability, which have shown great promise for disease theranostics. This review summarizes the recent achievements of organic phototheranostic agents and applications, especially which rationally utilize energy dissipation pathways of Jablonski diagram to modulate the fluorescence emission, photoacoustic/photothermal production, and photodynamic processes. Of particular interest are the systems exhibiting huge differences in aggregate state as compared with the solution or single molecule form, during which the intramolecular motions play an important role in regulating the photophysical properties. The recent advances from such an aspect for biomedical applications including high‐resolution imaging, activatable imaging and therapy, adaptive theranostics, image‐guided surgery, immunotherapy, and afterglow imaging are discussed. A brief summary and perspective in this field are also presented. We hope this review will be helpful to the researchers interested in bioprobe design and theranostic applications, and inspire new insights into the linkage between aggregate science and biomedical field.

Because of the mounting prevalence of complicated infections induced by multidrug-resistant bacteria, it is imperative to develop innovative and efficient antibacterial agents. In this work, we design a novel polymeric micelle for simultaneous decorating of silver nanoparticles and encapsulating of curcumin as a combination strategy to improve the antibacterial efficiency. In the constructed combination system, silver nanoparticles were decorated in the micellar shell because of the in situ reduction of silver ions, which were absorbed by the poly(aspartic acid) (PAsp) chains in the shell. Meanwhile, natural curcumin was encapsulated into the poly(ε-caprolactone) (PCL) core of the micelle through hydrophobic interaction. This strategy could prevent aggregation of silver nanoparticles and improve the water solubility of curcumin at the same time, which showed enhanced antibacterial activity toward Gram-negative P.aeruginosa and Gram-positive S.aureus compared with sliver-decorated micelle and curcumin-loaded micelle alone, due to the cooperative antibacterial effects of the silver nanoparticles and curcumin. Furthermore, the achieved combinational micelles had good biocompatibility and low hemolytic activity. Thus, our study provides a new pathway in the rational design of combination strategy for efficiently preventing the ubiquitous bacterial infections.