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Nanotheranostics 2024; 8(4): 442-457. [Abstract] [Full text] [PDF]
Nanotheranostics 2024; 8(4): 427-441. [Abstract] [Full text] [PDF]
International Journal of Biological Sciences
International Journal of Medical Sciences
Global reach, higher impact
Theranostics 2021; 11(4):1721-1731. doi:10.7150/thno.54930 This issue Cite
Research Paper
Dual-mode endogenous and exogenous sensitization of tumor radiotherapy through antifouling dendrimer-entrapped gold nanoparticles
1. State Key Laboratory for Modification of Chemical Fiber and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
2. Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, People's Republic of China.
Abstract
Development of a powerful sensitization system to alleviate radioresistance for enhanced tumor radiotherapy (RT) remains to be explored. Herein, we present a unique dual-mode endogenous and exogenous nanosensitizer based on dendrimer-entrapped gold nanoparticles (Au DENPs) to realize enhanced tumor RT.
Methods: Generation 5 poly(amidoamine) dendrimers partially modified with 1,3-propanesultone were used for templated synthesis of Au NPs, and the created zwitterionic Au DENPs were adopted for serum-enhanced delivery of siRNA to lead to the knockdown of hypoxia-inducible factor-1α (HIF-1α) protein and downstream genes to relieve tumor invasion. The Au DENPs/siRNA polyplexes were also used for dual-mode endogenous and exogenous sensitization of tumor RT in vivo.
Results: Due to the dual-mode endogenous sensitization through HIF-1α gene silencing and the exogenous sensitization through the existing Au component, enhanced RT of cancer cells in vitro and a tumor model in vivo can be realized, which was confirmed by enhanced cytotoxic reactive oxygen species (ROS) generation in vitro and double-strand DNA damage verified from the γ-H2AX protein expression in tumor cells in vivo. By integrating the advantages of HIF-1α gene silencing-induced downregulation of downstream genes and the dual-mode sensitization-enhanced RT, simultaneous inhibition of primary tumors and metastasis can be readily realized.
Conclusions: The developed zwitterionic Au DENPs may be used as a promising platform for dual-mode endogenously and exogenously sensitized RT of other tumor types.
Keywords: dendrimers, gold nanoparticles, HIF-1α siRNA, gene silencing, radiotherapy
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