Three stage rockets deliver platinum bombs against cancer
The research group led by Prof. WANG Jun at University of Science and Technology of China in collaboration with the group led by Prof. NIE Shuming at Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, has invented a “nano-aircraft carrier” drug delivery system, to deliver the anticancer drug more accurately and effectively to the cancer cells. This work was published online in Proceedings of the National Academy of Sciences of the United States of America (PNAS, doi: 10.1073/pnas.1522080113) on March 28, 2016.
A principal goal of cancer nanomedicine is to deliver therapeutics effectively to cancer cells within solid tumors. However, there are series of biological barriers that impede nanomedicine from reaching target cells. Larger nanoparticles, despite being more advantageous for improved pharmacokinetics and high propensity of vascular extravasation, are inherently unfavorable for tumor penetration due to their huge diffusional hindrance in the tumor interstitial space. In contrast, smaller nanoparticles show much better tumor penetration, but very small particles typically suffer from short half-life and insufficient tumor accumulation because of their rapid clearance, resulting in failure of cancer treatment.
These groups developed a stimuli-responsive clustered nanoparticles to systematically overcome these multiple barriers to cancer chemotherapy, via integrating multiple small nano-prodrug (~ 5 nm) onto one large nanocarrier (~ 90 nm), to obtained a clustered multistage drug delivery system. At physiological pH, the clustered nanoparticles hold the size around 100 nm, and have high propensity of long blood circulation and enhanced tumor accumulation through the EPR effect. Then, the acidic tumor extracellular pH (pHe, ~ 6.5–7.2) triggers the release of small nano-prodrugs (~ 5 nm), which enable to execute deep and uniform tumor penetration to reach more cancer cells. Finally, the nano-prodrugs can be rapidly reduced in the reductive cytosol to release active and potent cisplatin to kill cancer cells and lead to robust antitumor efficacy
The co-first author of this study is Mr. LI Hongjun (Ph.D.candidate) and Dr.DU Xiaojiao from Prof. WANG Jun’s group and Dr.DU Jinzhi from Prof. NIE Shuming’s group.
This work was financially supported by the National Basic Research Program of China, National Natural Science Foundation of China.
Publication link: http://www.pnas.org/content/early/2016/03/23/1522080113.abstract