Oxygen nanobubbles of ICG dimers achieve self-cascade photothermal and photodynamic therapy for hypoxia-reversible tumor treatment

Xiang Sun^¹, Zheng Zhang^², Moran Wang^¹, Yuqin Chen^¹, Xiang Meng^¹, Wenjun Zhao^¹, Juan Jin^¹, Wanghanqi Yang^¹, Chengwan Xia^²

(), Yuxin Wang^², Shengliang Li^³

(), Bin Huang^¹

(), Ning Gu^{¹^,⁴}

()

1Key Laboratory for Bio-Electromagnetic Environment and Advanced Medical Theranostics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing 210029, China

2Department of Oral and Maxillofacial Trauma Orthognathic Plastic Surgery, Nanjing Stomatological Hospital, Research Institute of Stomatology, Medical School of Nanjing University, Nanjing 210093, China

3College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China

4Nanjing Key Laboratory for Cardiovascular Information and Health, Engineering Medicine Institute of Clinical Medicine, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China

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A proof-of-concept of self-cascade photothermal and photodynamic therapy (PTT and PDT) was developed for hypoxia-reversible tumor therapy.

Abstract

Simultaneous photothermal and photodynamic therapies (PTT and PDT) hold great promise for noninvasive tumor therapy. However, effective regulation of PTT and PDT with optimal synergistic effects remains a challenge. To date, there are only a few synergistic PTT and PDT methods with suitable collaborative effects due to the rarity of efficient nanoplatforms with good cascading properties. To overcome this limitation, a proof-of-concept of self-cascade PTT and PDT was developed for hypoxia-reversible tumor therapy. With the assembly of dimeric indocyanine green (DICG) with oxygen nanobubbles (O₂-NBs), DICG/O₂-NBs typically exhibit J-aggregates for significant PTT effects, with a high photothermal conversion efficiency of 51.45% under 880 nm light irradiation. Interestingly, the PTT performance of DICG/O₂-NBs can switch J-aggregates of DICG into DICG monomers with efficient O₂ gas liberation, while producing hydroxyl radicals for type I PDT. Additionally, the evolved DICG monomer reacts with the released O₂ to generate plenty of ¹O₂ for efficient type II PDT. With these advantages, the cascaded nanoplatform achieves good tumor targeting and biocompatibility, and thus has high tumor inhibition of 94.26%, with an obvious ability to reverse hypoxia. This work demonstrates the efficiency of self-cascade PTT and PDT nanomedicine for high-performance hypoxia-reversible tumor ablation, thus providing a new approach for the development of cascading phototheranostics in vivo.

Keywords

indocyanine green (ICG) dimer oxygen nanobubble J-aggregate self-cascade photothermal therapies (PTT)photodynamic therapies (PDT)

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References

[1]

Fan, W. P.; Yung, B.; Huang, P.; Chen, X. Y. Nanotechnology for multimodal synergistic cancer therapy. Chem. Rev. 2017, 117, 13566–13638.