Delivering Singlet Oxygen in Dark Condition With an Anthracene-Functionalized Semiconducting Compound for Enhanced Phototheranostics

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.

Enhancing Fractionated Cancer Therapy: A Triple-Anthracene Photosensitizer Unleashes Long-Persistent Photodynamic and Luminous Efficacy

“…These agents do not generate ROS during the dark intervals (Table S1). − The lack of ROS production in these periods potentially allows cellular mechanisms to repair sublethal photodamage incurred during prior irradiation, thereby reducing the cytotoxic impact of subsequent light exposure and compromising the overall therapeutic outcome . Moreover, the photosensitizers currently employed in fractionated PDT are devoid of built-in imaging capabilities, which poses a significant obstacle in providing real-time feedback on critical treatment parameters, such as the optimal duration and frequency of irradiation intervals (Table S1).…”

Synthesis of a new photosensitizer for photodynamic and photothermal synergistic cancer therapy

“…[22][23][24][25] They are usually combined with drug delivery, afterglow imaging and photodynamic therapy. [26][27][28][29][30][31][32][33] For example, Chen et al reported an in situ polymerization in perylene diimide hybridized hollow mesoporous organosilica nanoparticles for phototheranostics. 34 Among the various semiconducting compounds, heavy atom free compounds can minimize the potential dark toxicity of the photosensitizers and reduce the systemic toxicity.…”

Porphyrin–anthracene covalent organic frameworks for sustainable photosterilization

“…14,15 For example, polycyclic aromatic derivatives such as anthracene and naphthalene can capture 1 O 2 to form corresponding EPOs, and the obtained EPOs can further release 1 O 2 efficiently through the thermal cycloreversion reactions without side reactions. [16][17][18][19][20][21] It has also been reported that EPOs can produce 1 O 2 , which leads to cell death through a process similar to apoptosis. 7,[22][23][24] It is worth mentioning that the combination of PSs and 1 O 2producing molecules from chemical sources is a more sensible way to achieve sustainable phototherapy treatment without continuous irradiation.…”