2012年1月，Bio-X交叉科学研究部王均教授研究组在ACS NANO上发表题为Sheddable Ternary Nanoparticles for Tumor Acidity-Targeted siRNA Delivery的论文。

Source: ACS NANO Volume: 6 Issue: 1 Pages: 771-781 DOI: 10.1021/nn204240b Published: JAN 2012
Yang, XZ (Yang, Xian-Zhu)1,2,3; Du, JZ (Du, Jin-Zhi)4; Dou, S (Dou, Shuang)1,2; Mao, CQ (Mao, Cheng-Qiong)1,2; Long, HY (Long, Hong-Yan)4; Wang, J (Wang, Jun)1,2
Addresses:
1. Univ Sci & Technol China, CAS Key Lab Brain Funct & Dis, Hefei 230027, Anhui, Peoples R China
2. Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China
3. Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China
4. Univ Sci & Technol China, Dept Polymer Sci & Engn, Hefei 230026, Anhui, Peoples R China
E-mail Address: jwang699@ustc.edu.cn

Reprint Address: Wang, J (reprint author), Univ Sci & Technol China, CAS Key Lab Brain Funct & Dis, Hefei 230027, Anhui, Peoples R China

Abstract: 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.