Stable Organic Photosensitizer Nanoparticles with Absorption Peak beyond 800 Nanometers and High Reactive Oxygen Species Yield for Multimodality Phototheranostics

Abstract

Effective multimodality phototheranostics under deep-penetration laser excitation is highly desired for tumor medicine, which is still at a deadlock due to lack of versatile photosensitizers with absorption located in the long-wavelength region. Herein, we demonstrate a stable organic photosensitizer nanoparticle based on molecular engineering of benzo[c]thiophene (BT)-based photoactivated molecules with strong wavelength-tunable absorption in the near-infrared region. Via molecular design, the absorption and singlet oxygen generation of BT molecules would be reliably tuned. Importantly, the nanoparticles with a red-shifted absorption peak of 843 nm not only show over 10-fold reactive oxygen species yield compared with indocyanine green but also demonstrate a notable photothermal effect and photoacoustic signal upon 808 nm excitation. The in vitro and in vivo experiments substantiate good multimodal anticancer efficacy and imaging performance of BT theranostics. This work provides an organic photosensitizer nanoparticle with long-wavelength excitation and high photoenergy conversion efficiency for multimodality phototherapy.

Thermally Activated Delayed Fluorescence Material: An Emerging Class of Metal‐Free Luminophores for Biomedical Applications

“…Photodynamic therapy (PDT) with their unique merits of non‐invasion, high specificity, minimal drug resistance, and low side effects, has been approved for clinical utilization in 1993, emerging as one of the most promising modalities for cancer therapeutics. [ 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 ] In PDT, the photosensitizers (PSs) are excited by photons to transfer energy to the surrounding ground state triplet oxygen ( 3 O 2 ) for the formation of singlet oxygen ( 1 O 2 ), which will damage tumor cells. [ 58 , 59 , 133 , 134 ] As indicated above, the photophysical mechanism of TADF materials in PDT elaborates that an effectual ISC process is highly essential for 1 O 2 generation.…”

Aggregation-Induced Fluorogens in Bio-Detection, Tumor Imaging, and Therapy: A Review

“…91,92 During the PDT, the photosensitizers (PS) induce the generation of reactive oxygen species (ROS) to kill the cells. 93 However, the traditional PS suffer from the ACQ, thus cannot kill cancer cells by reactive oxygen species. 94 The PS of the material is improved via promoting the intersystem crossing (ISC) processes.…”

“…97,98 The PS active AIE NPs induced intracellular ROS generation (such as superoxide anion radicals/ •O 2 −,hydroxyl radicals /•OH, hydrogen peroxide radicals /•H 2 O 2 , and singlet oxygen /1O 2 ) under light irradiation, to cause phototoxicity of cancer cells by apoptosis and necrosis. 93,94,24 Our group recently developed a novel two-photon AIE PS-lipid NPs with AIE characteristics for image guided-PDT of cancer. 24 The AIEgens are precipitated with lipids (Figure 6a) to form a nanoparticle structure of diameter 178 nm (Figure 6b).…”

Smart Nanoparticles for Chemo-Based Combinational Therapy

“…Photo-absorbing agents absorb light irradiation and convert such optical energy into heat, while photosensitizers absorb light irradiation and generate ROS. From the perspective of materials, photoactive agents include inorganic materials, organic small molecules [84,85], and conjugated polymers [86].…”