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A novel hierarchical targeting and controllable smart nanoparticles for enhanced in situ nuclear photodynamic therapy

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Abstract

Photodynamic therapy (PDT) is a promising and non-invasive treatment for various cancers. Although nuclear PDT has considerable therapeutic prospects, it is still hindered by the non-specific recognition of tumor tissues or the degradation of nuclear targeting cationic groups by enzymes in the blood. Herein, a hierarchical targeted and controlled release strategy is proposed by using folate-modified poly-β-cyclodextrin (poly-β-CD) as a nano-carrier for loading nuclear localization signals (NLSs)-conjugated photosensitizer PAP (PAP = pyropheophorbide a—PAAKRVKLD). Excitingly, the obtained FA-CD@PAP (FA = folic acid) and nanoparticles (NPs) can specifically recognize tumor cells overexpressing folate receptors (FR) to remarkedly enhance the intracellular accumulation. Furthermore, the encapsulated PAP can be released under acidic conditions to realize precise nuclear localization. The reactive oxygen species (ROS) generated by the intranuclear-accumulated PAP upon irradiation can oxidize and destroy DNA chains or DNA repair enzymes instantaneously, which can directly induce cell death. As a result, FA-CD@PAP NPs exhibit excellent tumor regression and negligible side effects. This work provides an intelligent nuclear-targeted delivery strategy for in situ nuclear PDT with extremely prominent efficacy and high biological safety.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Nos. 81703345 and 21974009), the Natural Science Foundation of Fujian Province (No. 2021J01549) and the National Health and Family Planning Commission Jointly established a scientific research fund (No. WKJ2016-2-14). We thank Servicebio Co., Ltd. (Wuhan, China) for technical support on tissue sections and fluorescent staining during in vivo experiments.

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  1. National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350116, China

    Gankun Yuan, Qilu Wang, Zifan You, Xuening Chen, Jinping Xue, Xiao Jia & Juanjuan Chen

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  1. Gankun Yuan
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Yuan, G., Wang, Q., You, Z. et al. A novel hierarchical targeting and controllable smart nanoparticles for enhanced in situ nuclear photodynamic therapy. Nano Res. 15, 4212–4223 (2022). https://doi.org/10.1007/s12274-021-4027-2

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