Nanotheranostics 2017; 1(4):346-357. doi:10.7150/ntno.19380


Be Active or Not: the Relative Contribution of Active and Passive Tumor Targeting of Nanomaterials

Rui Li1, Ke Zheng2, Cai Yuan2, Zhuo Chen3, Mingdong Huang2, 3✉

1. Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, Henan, 450002, China;
2. Fuzhou University, Fuzhou, Fujian, 350116, China;
3. Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, 350002, China.


Malignant tumor (cancer) remains as one of the deadliest diseases throughout the world, despite its overall mortality drops. Nanomaterials (NMs) have been widely studied as diagnostic and/or therapeutic agents for tumors. A feature of NMs, compared to small molecules, is that NMs can be concentrated passively in tumors through enhanced permeability and retention (EPR) effect. In the meantime, NMs can be engineered to target toward tumor specific markers in an active manner, e.g., receptor-mediated targeting. The relative contribution of the EPR effect and the receptor-mediated targeting to NM accumulation in tumor tissues has not been clearly defined yet. Here, we tackle this fundamental issue by reviewing previous studies. First, we summarize the current knowledge on these two tumor targeting strategies of NMs, and on how NMs arrive to tumors from blood circulation. We then demonstrate that contribution of the active and passive effects to total accumulation of NMs in tumors varies with time. Over time, the receptor-mediated targeting contributes more than the EPR effect with a ratio of 3 in the case of urokinase-type plasminogen activator receptor (uPAR)-mediated targeting and human serum albumin (HSA)-mediated EPR effect. Therefore, this review highlights the dynamics of active and passive targeting of NMs on their accumulation at tumor sites, and is valuable for future design of NMs in cancer diagnosis and treatment.

Keywords: nanomaterial, nanoparticle, enhanced permeability and retention effect, receptor-mediated tumor targeting, urokinase-type plasminogen activator receptor, amino-terminal fragment.

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How to cite this article:
Li R, Zheng K, Yuan C, Chen Z, Huang M. Be Active or Not: the Relative Contribution of Active and Passive Tumor Targeting of Nanomaterials. Nanotheranostics 2017; 1(4):346-357. doi:10.7150/ntno.19380. Available from