Identification of a mitochondria-targeting fluorescent small molecule for dual phototherapy

Jie Chen,Yu Wang,Chunmeng Shi,Shenglin Luo,Lei Long,Xu Tan,Lang Liu,Zujuan Liu

doi:10.1142/s1793545818500165

Jie Chen, Yu Wang + Show 6 more

Open Access

https://doi.org/10.1142/s1793545818500165

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Abstract

Phototherapy, mainly including photodynamic therapy (PDT) and photothermal therapy (PTT), is a noninvasive and effective approach for cancer treatment. Since integration of PDT and PTT for simultaneous synergistic PDT/PTT treatment enables us to improve phototherapeutic efficacy significantly, it has been attracting a lot of investigations in current days. Here, we introduce IR-52, a new mitochondria-targeting near infrared (NIR) fluorescent small molecule, which possesses structure-inherent PTT and PDT synergistic phototherapeutic effects without conjugation to specific ligands. After NIR light irradiation (808[Formula: see text]nm, 2[Formula: see text]W/cm2, 5[Formula: see text]min), both the hyperthermia and excessive singlet oxygen levels were determined when dissolving IR-52 in aqueous solutions. In vitro photoinduced cytotoxicity studies showed significant lower cell viabilities and higher necrotic/apoptotic rates when cancer cells were treated with IR-52 and irradiation, and its’ mitochondrial localization in cancer cells would partially explain its high cytotoxicity. Further in vivo synergetic PDT and PTT effects were demonstrated by high tumor surface temperature and significant inhibition of tumor growth. Our results strongly suggest that IR-52, which possesses excellent photosensitivity, may provide a promising strategy for tumor treatment with decreased side effects.

Highlights

Phototherapy has become one of the main means for cancer treatment available in clinic following with surgical treatment, chemotherapy and radiotherapy
The typical way to improve the specicity is to conjugate the PSs with a target ligand, which can bind to the cancer cells overexpressed biomarkers e±ciently.[14,15]
We developed a lipophilic cationic heptamethine dye, IR-52, with a peak optical absorption of 789 nm wavelength, which can preferentially accumulate at tumor site and further retain in the mitochondria of cancer cells and is excited with 808 nm laser to generate potent local heat and singlet oxygen, destroying cancer cells both in vitro and in vivo via its simultaneous synergistic photodynamic therapy (PDT)/photothermal therapy (PTT) property

Summary

Introduction

Phototherapy has become one of the main means for cancer treatment available in clinic following with surgical treatment, chemotherapy and radiotherapy. This type of light-triggered treatment has remarkably improved selectivity and reduced the side e®ects as compared to conventional therapies.[1,2,3] Phototherapy mainly includes photodynamic therapy (PDT) and photothermal therapy (PTT).[4,5] For PDT or PTT, the key factor to determine their therapeutic e®ects is the photosensitizer (PS).[6,7,8] A desirable PS should have superior photosensitivity to ensure the phototherapeutic e®ect and high specicity to reduce the side e®ects.[9,10,11] The most common way to enhance the photosensitivity is to synthesis a photothermal PS and a photodynamic PS together as reported in many nanomaterials.[12,13] The typical way to improve the specicity is to conjugate the PSs with a target ligand, which can bind to the cancer cells overexpressed biomarkers e±ciently.[14,15] there are still many problems for these nanomaterial-based multifunctional PSs, such as poor tumor-targeting activity, unsatised high-quality control during large-scale preparation, potential long-term toxicity concerns, which lead to the di±culties for further clinical application.[16,17]

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Conclusion