Abstract
Photodynamic therapy (PDT) utilizes the photogeneration of reactive oxygen species (ROS) with high cytotoxicity to kill cancer cells, holding great promise for cancer treatment. Fractionated delivery of singlet oxygen (1O2) is a wise approach to relieving hypoxia, thus enhancing the therapeutic efficacy. In this article, an anthracene-functionalized semiconducting compound (DPPA) has been designed and synthesized. With irradiation, the compound is able to undergo efficient intersystem crossing (ISC) and non-radioactive decay for photodynamic/photothermal synergistic therapy. In addition, the anthracene module is able to capture and release 1O2 reversibly with or without irradiation. DPPA nanoparticles (NPs) obtained by nanoprecipitation with DSPE-PEG exhibit considerable high phototoxicity on human kidney cancer cells (A498), and the half maximum inhibitory concentration (IC50) is 15.8 μg/ml. Furthermore, an in vivo study demonstrates that complete tumor suppression was observed when the mice were administered DPPA NPs with the help of laser, compared with the control and dark groups. The H&E analysis of the normal tissues (the heart, liver, spleen, lungs, and kidney) indicates that such NPs cause no side effects, indicating the biosafety of DPPA NPs. The results provide a strategy to design a heavy-atom–free photosensitizer for photothermal and fractionated PDT against kidney tumors.
Highlights
With the increasing cases of cancer worldwide, the development of new therapeutic methods for cancer treatment is of tremendous significance. (Siegel et al, 2021)
The morphology characterized by a transmission electron microscope (TEM) suggests DPPA is self-assembled to form uniform NPs (Figure 1C), consisting with the dynamic light-scattering (DLS) result (Figure 1D)
Based on the singlet oxygen detection and photothermal conversion efficiency investigation, we evaluated the therapeutic efficacy of DPPA NPs in vitro
Summary
With the increasing cases of cancer worldwide, the development of new therapeutic methods for cancer treatment is of tremendous significance. (Siegel et al, 2021). Chen et al designed a heavy-atom-free compound for efficient singlet oxygen generation and continuous PDT. DPPA nanoparticles (NPs) obtained by nanoprecipitation exhibit spherical morphology with an average diameter of 52 nm Such NPs are able to capture singlet oxygen with irradiation and release it in the dark condition. In vitro MTT assay indicates the half maximum inhibitory concentration (IC50) of DPPA NPs is as low as 15.8 μg/ml in human kidney cells (A498) with laser irradiation. The medium was discarded, and the cells were washed with PBS (1 ml, 3 times), followed by the co-culture with 1 ml polyoxymethylene for 25 min. For the dark and illumination groups, the mice were intravenously injected DPPA NPs (200 μg/ml, 100 μL). Statistical analysis was performed by GraphPad Prism 6.0. p values of less than 0.05 were considered significant (*p < .05, **p < .01, ***p < .001)
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