2011年2月，我室Bio—X交叉科学研究部王均教授研究组与人合作在ACS NANO上发表题为Simultaneous Delivery of siRNA and Paclitaxel via a "Two-in-One" Micelleplex Promotes Synergistic Tumor Suppression的论文。

Source: ACS NANO Volume: 5 Issue: 2 Pages: 1483-1494 Published: FEB 2011

Sun TM (Sun, Tian-Meng)4,5, Du JZ (Du, Jin-Zhi)6,7, Yao YD (Yao, Yan-Dan)1, Mao CQ (Mao, Cheng-Qiong)4,5, Dou SA (Dou, Shuang)4,5, Huang SY (Huang, Song-Yin)1, Zhang PZ (Zhang, Pei-Zhuo)2, Leong KW (Leong, Kam W.)3, Song EW (Song, Er-Wei)1, Wang J (Wang, Jun)

Addresses:
1. Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou 510120, Guangdong Peoples R China
2. Suzhou GenePharma Co Ltd, Suzhou 215123, Jiangsu Peoples R China
3. Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA
4. Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui Peoples R China
5. Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui Peoples R China
6. Univ Sci & Technol China, Dept Polymer Sci & Engn, Hefei 230026, Anhui Peoples R China
7. Univ Sci & Technol China, CAS Key Lab Soft Matter Chem, Hefei 230026, Anhui Peoples R China
E-mail Addresses: songerwei02@yahoo.com.cn, jwang699@ustc.edu.cn

Reprint Address: Song, EW (reprint author), Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou 510120, Guangdong Peoples R China

Abstract:
Combination of two or more therapeutic strategies with different mechanisms can cooperatively prohibit cancer development. Combination of chemotherapy and small interfering RNA (siRNA)-based therapy represents an example of this approach. Hypothesizing that the chemotherapeutic drug and the siRNA should be simultaneously delivered to the same tumoral cell to exert their synergistic effect, the development of delivery systems that can efficiently encapsulate two drugs and successfully deliver payloads to targeted sites via systemic administration has proven to be challenging. Here, we demonstrate an innovative "two-in-one" micelleplex approach based on micellar nanoparticles of a biodegradable triblock copolymer poly(ethylene glycol)-b-poly(epsilon-caprolactone)-b-poly(2-aminoethyl ethylene phosphate) to systemically deliver the siRNA and chemotherapeutic drug. We show clear evidence that the micelleplex is capable of delivering siRNA and paditaxel simultaneously to the same tumoral cells both In vitro and in vivo. We further demonstrate that systemic administration of the micelleplex carrying polo-like kinase 1 (PIk1) specific siRNA and paditaxel can induce a synergistic tumor suppression effect in the MDA-MB-435s xenograft murine model, requiring a thousand-fold less paditaxel than needed for paditaxel monotherapy delivered by the micelleplex and without activation of the Innate immune response or generation of carrier-associated toxicity.