Precise Molecular Engineering of Photosensitizers with Aggregation‐Induced Emission over 800 nm for Photodynamic Therapy

Abstract

Owing to efficient singlet oxygen ( 1 O 2 ) generation in aggregate state, photosensitizers (PSs) with aggregation-induced emission (AIE) have attracted much research interests in photodynamic therapy (PDT). In addition to high 1 O 2 generation efficiency, strong molar absorption in longwavelength range and near-infrared (NIR) emission are also highly desirable, but difficult to achieve for AIE PSs since the twisted structures in AIE moieties usually lead to absorption and emission in short-wavelength range. In this contribution, through acceptor engineering, a new AIE PS of TBT is designed to show aggregation-induced NIR emission centered at 810 nm, broad absorption in the range between 300 and 700 nm with a large molar absorption coefficient and a high 1 O 2 generation efficiency under white light irradiation. Further, donor engineering by attaching two branched flexible chains to TBT yielded TBTC8, which circumvented the strong intermolecular interactions of TBT in nanoparticles (NPs), yielding TBTC8 NPs with optimized overall performance in 1 O 2 generation, absorption, and emission. Subsequent PDT results in both in vitro and in vivo studies indicate that TBTC8 NPs are promising candidates in practical application.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adfm.201901791.(ROS) to kill cancer cells under light irradiation, has drawn widespread research interests owing to its good spatiotemporal precision, precise controllability, and noninvasiveness, etc. [1] Among which, the process that using emissive PSs as the key agents to find out the tumor site first and then realize PDT has been recognized as cost-effective and time-saving due to the integration of both diagnosis and treatment in one molecule. [2] To achieve effective PDT, smart design of PSs is of essential significance. Ideal properties of PSs include efficient 1 O 2 generation ability for cancer cell ablation, near-infrared (NIR) emission for imaging, strong absorption in long wavelength for easy excitation and good penetration depth, negligible dark toxicity for minimal side effects, and good photostability for continuous light irradiation. [3] Boron-dipyrromethene (BODIPY) derivatives, [4] metal complexes, [5] cyanine derivatives, [6] and porphyrin or chlorin derivatives, [7] are some typical traditional PSs. Heavy atoms are usually used to improve the 1 O 2 generation efficiency of BODIPY derivatives and metal complexes, which usually exhibit nontrivial dark toxicity with weak fluorescence. [4,5] Cyanine-type PSs are famous for their large absorbance in long-wavelength range with bright NIR emission over 800 nm. However, their poor 1 O 2 production capability and low photostability limited their practical application. [6] Porphyrin and chlorin derivatives usually show good 1 O 2 generation, but their light-absorbing capacity in long-wavelength range is generally rather poor, and their emission peaks are relatively blue as compared to those of cyanine-type PSs. [7] Several ...

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Bioorthogonal Coordination Polymer Nanoparticles with Aggregation‐Induced Emission for Deep Tumor‐Penetrating Radio‐ and Radiodynamic Therapy

“…[ 9 ] However, for PDT, the excitation of AIE PSs was still limited to the short wavelength range, as a result of their rotor structures and the AIE PS design strategy. [ 10 ] We hypothesized that coordination of AIE PSs to the ions of a high‐ Z element would allow us to address this limitation and realize RDT with enhanced penetration and efficient SO production.…”

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“…Unfortunately, PDT still faces certain limitations, including the selection of effective photosensitizers, administration of light doses and the enormous limitation of tumor hypoxia 10 , 11 . Up to now, great strides and achievements have been made to conduct research on the photosensitizers and light doses 12 , 13 , 14 , 15 . However, there are still many challenges ahead of us in modulating hypoxia for enhancing PDT.…”