Jun Liu

Radio imaging and optical imaging offer complementary advantages for biomedical diagnosis. However, the photosensitizers used in imaging must be degraded to reduce phototoxicity during phototherapy. Herein, we report a novel dicyanomethylene-based near-infrared photosensitizer (PS) that self-degrades via multiple pathways, including hydrolysis, aggregation-induced photodegradation, and oxidation by hypochlorous acid. To meet diverse theranostic requirements, the degradation behavior and performance of the PS were systematically regulated through co-assembly with three carriers. First, co-assembly with DSPE-PEG2000 produced a nanosystem that is stable to laser irradiation and water during multimodal diagnosis, and labeling with 64Cu enabled dual-mode photoacoustic and radio signal imaging. Second, co-assembly with PLGA-PEG5000 reduced the photodegradation rate by enabling complete degradation through hydrolysis, thereby facilitating deep-tumor phototherapy. Third, complexation with cucurbit[8]uril (CB[8]) selectively inhibited the hydrolytic properties of the photosensitizer, thereby reducing its phototoxicity through photodegradation and oxidative degradation pathways when superficial tumors are subjected to phototherapy. The phototherapeutic efficacy of the designed nanosystems was validated in a subcutaneous 4T1 tumor-bearing mouse model. The results demonstrated effective tumor inhibition with minimal phototoxicity, confirming the suitability of the developed system for safe phototherapy. Overall, this work presents a rational strategy for tuning photosensitizer degradation pathways to balance imaging performance, therapeutic efficacy, and biosafety, providing a versatile platform for multimodal theranostic applications.

Schematic representation of synthesis of ^99m Tc/NIR-II NPs with SPECT and NIR-II fluorescence imaging capabilities for SLN.

Single-wavelength lasers that trigger intelligently designed multifunctional theranostic nanoplatforms are urgently needed for early cancer diagnosis and imaging-guided therapy. In this study, a novel zinc porphyrin, Por-TR, was fabricated by incorporating thiophene as a donor and introducing electron acceptors on both sides to expand the conjugation. The presence of multiple flexible chains in the molecular structure of Por-TR inhibits π-π stacking, which allows it to form J nanoaggregates when coassembled with DSPE-PEG2000, demonstrating maximum absorption at approximately 808 nm. These Por-TR NPs provide NIR-II fluorescence/PA dual-modal signals for imaging and serve as a combined PTT/PDT therapeutic agent, making them a suitable multifunctional theranostic nanoplatform. To further improve their therapeutic effects, we embedded a thermosensitive NO donor, BNN6, in the Por-TR nanosystem to achieve combined PDT/PTT/NO therapy. Intravenous injection of Por-TR-NO NPs into 4T1 tumor-bearing mice enabled the accurate observation of tumor location via NIR-II fluorescence/PA dual-modal imaging. In vivo therapy results show that the Por-TR-NO NPs exhibited remarkable antitumor efficacy in combined PTT/PDT/NO therapy, which was triggered by an 808 nm laser. Overall, this nanoplatform offers a versatile approach to cancer diagnosis and treatment.