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Phototheranostic Zinc Porphyrin Nanoparticles Triggered by an 808 nm Laser: NIR-II Fluorescence/Photoacoustic Imaging-Guided Combined Photothermal/Photodynamic/NO Therapy

Hongyu ChenSchool of Pharmacy and Institute of Pharmacy, Medical Imaging Key Laboratory of Sichuan Province, Thyroid and Breast Surgery, North Sichuan Medical CollegeXiaobo ZhaoSchool of Pharmacy and Institute of Pharmacy, Medical Imaging Key Laboratory of Sichuan Province, Thyroid and Breast Surgery, North Sichuan Medical CollegeAkbar HalimovInstitute of Electrical EngineeringMingkai FuChinese Academy of SciencesJing TuSchool of Pharmacy and Institute of Pharmacy, Medical Imaging Key Laboratory of Sichuan Province, Thyroid and Breast Surgery, North Sichuan Medical CollegeHui LiuSchool of Pharmacy and Institute of Pharmacy, Medical Imaging Key Laboratory of Sichuan Province, Thyroid and Breast Surgery, North Sichuan Medical CollegeHuajun XuShandong Provincial Key Laboratory for Science of Material Creation and Energy Conversion, Institute of Frontier Chemistry, School of Chemistry and Chemical EngineeringJun LiuAffiliated Hospital of North Sichuan Medical College
Bioconjugate Chemistryjournal2025en

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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.

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