Theranostics 2017; 7(5):1192-1203. doi:10.7150/thno.17881
Phosphorylcholine-based stealthy nanocapsules enabling tumor microenvironment-responsive doxorubicin release for tumor suppression
1. The Shenzhen Key Lab of Gene and Antibody Therapy and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P. R. China;
2. School of Life Sciences, Tsinghua University, Beijing 100084, PR China;
3. Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, P.R.China.
* These three authors contributed equally to this work.
The efficient delivery of anticancer drugs into tumor tissues to improve therapeutic efficacy remains an urgent demand. To satisfy this demand, a drug delivery system based on a stealthy nanocapsule was developed. This nanocapsule was fabricated by encapsulating stealthy cross-linked poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and benzaldehyde groups around the protein bovine serum albumin (BSA) followed by conjugation of doxorubicin (Dox) through a pH-responsive benzoic-imine bond. The in vitro results show that the Dox-conjugated nanocapsule (nBSA-Dox) released the drug under an acidic tumor microenvironment (pH ~6.5) and killed HepG2 human liver cancer cells. The half-life of Dox conjugated to nBSA in mice was significantly prolonged, and the area-under-curve of plasma Dox of the mice treated with nBSA-Dox was as much as 242 fold of free Dox. The in vivo results confirmed that this nanocapsule efficiently accumulated in tumor tissue and significantly suppressed the tumor growth.
Keywords: stealthy nanocapsule, tumor suppression, phosphorylcholine, tumor microenvironment, benzoic-imine bond.
Liu G, Tsai Hi, Zeng X, Zuo Y, Tao W, Han J, Mei L. Phosphorylcholine-based stealthy nanocapsules enabling tumor microenvironment-responsive doxorubicin release for tumor suppression. Theranostics 2017; 7(5):1192-1203. doi:10.7150/thno.17881. Available from http://www.thno.org/v07p1192.htm