期刊
NANO RESEARCH
卷 15, 期 5, 页码 4212-4223出版社
TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-021-4027-2
关键词
photodynamic therapy; hierarchical targeted; nuclear localization signal; poly-beta-cyclodextrin; nuclear-targeted
类别
资金
- National Natural Science Foundation of China [81703345, 21974009]
- Natural Science Foundation of Fujian Province [2021J01549]
- National Health and Family Planning Commission [WKJ2016-2-14]
The study introduces a targeted PDT strategy using folate-modified poly-beta-cyclodextrin as a carrier, demonstrating high biological safety and efficacy in nuclear-targeted treatment.
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-beta-cyclodextrin (poly-beta-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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