期刊
ACS NANO
卷 6, 期 1, 页码 771-781出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn204240b
关键词
sheddable nanoparticles; pH-responsive; tumor acidity; siRNA delivery; nanotechnology
类别
资金
- National Basic Research Program of China (973 Programs) [2010CB934001, 2012CB932502]
- National Natural Science Foundation of China [51125012, 50733003]
- Fundamental Research Funds for the Central Universities (WK2070000008 [WK2070000008]
- State Key Laboratory of Supramolecular Structure and Materials [SKLSSM201117]
Drug delivery systems for cancer therapy usually need to be sterically stabilized by a poly(ethylene glycol) (PEG) layer during blood circulation to minimize nonspecific interactions with serum components. However, PEGylation significantly reduces cellular uptake of the delivery systems after they accumulate at the tumor site, which markedly impairs the in vivo antitumor efficiency. Here, we develop a ternary small Interfering RNA (siRNA) delivery system with tumor acidity-activated sheddable PEG layer to overcome the challenge. The sheddable nanoparticle is fabricated by Introducing a tumor acidity-responsive PEGylated anionic polymer to the surface of positively charged polycation/siRNA complexes via electrostatic interaction. We show clear evidence that introducing the PEGylated anionic polymer to the surface of a nanoparticle markedly reduces its nonspecific interactions with protein. We further demonstrate that the nanoparticle Is capable of deshielding the PEG layer at the slightly acidic tumor extracellular microenvironment to facilitate the delivery of siRNA to the tumor cells after accumulation at the tumor site. Accordingly, this promotes the RNA-interfering efficiencies and enhances the Inhibition of tumor growth. Such delivery system with the ability to deshleld the PEG layer at the target tissues has remarkable potential in cancer therapy.
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