The development of a simple drug formulation capable of achieving both activatable type I photoreaction and tumor-responsive release of immunomodulator is crucial for advancing photodynamic immunotherapy (PDIT). Herein, we present a nanostructured photosensitizer (NP5) that is activated by the acidic tumor microenvironment to produce type I reactive oxygen species (ROS) under light irradiation and release the immunomodulator demethylcantharidin (DMC) for PDIT. The NP5 is formed by self-assembly of a versatile phthalocyanine molecule which is composed of DMC and phthalocyanine linked via a pH-responsive amide bond. NP5 produces minimal ROS under light irradiation at the condition of pH 7.4. However, NP5 can release DMC at the condition of pH 6.5 and concurrently trigger type I photoreactions. The results of in vivo experiments indicate that NP5-mediated PDIT induce the increase of cytotoxic T lymphocytes and decrease of regulatory T lymphocytes, which can effectively inhibit the bilateral tumor growth. This work is anticipated to serve as a reference for the development of innovative agents for precise PDIT of hypoxic tumors.
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| http://dx.doi.org/10.1016/j.jphotobiol.2024.113067 | DOI Listing |
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Article Synopsis
- - The study presents a novel Bodipy photosensitizer that is responsive to the hypoxic conditions of solid tumors, aiming to enhance both imaging and treatment efficiency in cancer therapy.
- - Upon activation by hydrogen peroxide (HO) found in tumors, the photosensitizer shows significantly improved fluorescence and reactive oxygen species (ROS) production, which contributes to its effectiveness in photodynamic therapy.
- - Experiments demonstrate that this photosensitizer rapidly accumulates in tumor cells, improves imaging signals, and effectively inhibits tumor growth, indicating its potential as a strong candidate for cancer theranostics.
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