Synergistic non-bonding interactions based on diketopyrrolo-pyrrole for elevated photoacoustic imaging-guided photothermal therapy

Conjugated polymers have excellent properties and can be used in photothermal therapy (PTT). Nevertheless, the concept to design and optimize the photothermal performance by cooperative non-bonding interactions is still in its infancy. Herein, a series of diketopyrrolopyrrole (DPP) derivatives containing chalcogen and fluorine atoms were synthesized to reveal how intra- and intermolecular interactions affect the therapeutic performance of cancer in vitro and in vivo. The synergistic pi-pi and FMIDLINE HORIZONTAL ELLIPSISH interactions facilitate fluorine and selenium-substituted DPP-SeF to elevate their photothermal conversion efficiency up to 62% from 32% without fluorine and selenium-substituted DPP-SS, and the half-maximal inhibitory concentration drops to similar to 8.36 mu g mL(-1) for DPP-SeF from 15.14 mu g mL(-1) for DPP-SS on A549 cells under 808 nm light irradiation. More interestingly, efficient tumor killing ability and magnificent biocompatibility on an animal model of A549 transplanted tumor reassert that DPP-SeF nanoagents have immense potential as photoacoustic/PTT agents. Thus, this work presents an efficient phototherapeutic agent, and meanwhile demonstrates the facile concept of accessing the synergistic effect of non-bonding interactions to promote antitumor efficiency by ingenious molecular engineering.

Automated summary

This work synthesized a series of DPP derivatives containing chalcogen and fluorine atoms, revealing the synergistic pi-pi and van der Waals interactions can enhance photothermal performance. The DPP-SeF nanoagents show efficient tumor killing ability and excellent biocompatibility, indicating their potential as photoacoustic/PTT agents in cancer treatment. The study demonstrates the concept of utilizing non-bonding interactions to optimize antitumor efficiency through molecular engineering.