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Abstract

Herein, we elucidated the mechanisms and key factors for the tumor-targeting ability of nanoparticles that presented high targeting efficiency for liver tumor. We used several different nanoparticles with sizes of 200-300 nm, including liposome nanoparticles (LNPs), polystyrene nanoparticles (PNPs) and glycol chitosan-5β-cholanic acid nanoparticles (CNPs). Their sizes are suitable for the enhanced permeation and retention (EPR) effect in literature. Different in vitro characteristics, such as the particle structure, stability, and bioinertness, were carefully analyzed with and without serum proteins. Also, pH-dependent tumor cell uptakes of nanoparticles were studied using fluorescence microscopy. Importantly, CNPs had sufficient stability and bioinertness to maintain their nanoparticle structure in the bloodstream, and they also presented prolonged circulation time in the body (blood circulation half-life T1/2 = about 12.2 h), compared to the control nanoparticles. Finally, employing liver tumor bearing mice, we also observed that CNPs had excellent liver tumor targeting ability in vivo, while LNPs and PNPs demonstrated lower tumor-targeting efficiency due to the nonspecific accumulation in normal liver tissue. Liver tumor models were produced by laparotomy and direct injection of HT29 tumor cells into the left lobe of the liver of athymic nude mice. This study provides valuable information concerning the key factors for the tumor-targeting ability of nanoparticles such as stability, bioinertness, and rapid cellular uptake at targeted tumor tissues. 

Author information

Na JH1,2,3, Koo H4, Lee S2,3, Han SJ1, Lee KE5, Kim S6, Lee H6, Lee S2,3, Choi K7, Kwon IC1,8, Kim K1.​

1Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST) , Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.

2The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine , 601 North Caroline Street, Baltimore, Maryland 21287, United States.

3The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine , 400 North Broadway, Baltimore, Maryland 21231, United States.

4Department of Medical Lifescience, College of Medicine, The Catholic University of Korea , 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.

5Advanced Analysis Center, Korea Institute of Science and Technology (KIST) , Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.

6Department of Chemistry and Institute for NanoCentury and BioCentury, Korea Advanced Institute of Science and Technology (KAIST) , 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Republic of Korea.

7Korea Institute of Science and Technology Europe (KIST-Europe) Forschungsgesellschaft mbH , Campus E7.1, 66123 Saarbrücken, Germany.

8KU-KIST School, Korea University , 1 Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea.