TY - JOUR
T1 - Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size
AU - Cabral, H.
AU - Matsumoto, Y.
AU - Mizuno, K.
AU - Chen, Q.
AU - Murakami, M.
AU - Kimura, M.
AU - Terada, Y.
AU - Kano, M. R.
AU - Miyazono, K.
AU - Uesaka, M.
AU - Nishiyama, N.
AU - Kataoka, K.
N1 - Funding Information:
The authors are grateful to S. Fukuda from the University of Tokyo Hospital for his valuable support in conducting transmission electron microscopy and to S. Ogura for assistance with animal care. This study was supported by the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program) from the Japan Society for the Promotion of Science (JSPS) and Grants-in-Aid for Scientific Research from the Japanese Ministry of Health, Labour, and Welfare. ν-SR-XRF studies were supported by the Nanotechnology Support Program of the Japan Synchrotron Radiation Research Institute (JASRI).
PY - 2011/12
Y1 - 2011/12
N2 - A major goal in cancer research is to develop carriers that can deliver drugs effectively and without side effects. Liposomal and particulate carriers with diameters of ∼100 nm have been widely used to improve the distribution and tumour accumulation of cancer drugs, but so far they have only been effective for treating highly permeable tumours. Here, we compare the accumulation and effectiveness of different sizes of long-circulating, drug-loaded polymeric micelles (with diameters of 30, 50, 70 and 100 nm) in both highly and poorly permeable tumours. All the polymer micelles penetrated highly permeable tumours in mice, but only the 30 nm micelles could penetrate poorly permeable pancreatic tumours to achieve an antitumour effect. We also showed that the penetration and efficacy of the larger micelles could be enhanced by using a transforming growth factor-β 2 inhibitor to increase the permeability of the tumours.
AB - A major goal in cancer research is to develop carriers that can deliver drugs effectively and without side effects. Liposomal and particulate carriers with diameters of ∼100 nm have been widely used to improve the distribution and tumour accumulation of cancer drugs, but so far they have only been effective for treating highly permeable tumours. Here, we compare the accumulation and effectiveness of different sizes of long-circulating, drug-loaded polymeric micelles (with diameters of 30, 50, 70 and 100 nm) in both highly and poorly permeable tumours. All the polymer micelles penetrated highly permeable tumours in mice, but only the 30 nm micelles could penetrate poorly permeable pancreatic tumours to achieve an antitumour effect. We also showed that the penetration and efficacy of the larger micelles could be enhanced by using a transforming growth factor-β 2 inhibitor to increase the permeability of the tumours.
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U2 - 10.1038/nnano.2011.166
DO - 10.1038/nnano.2011.166
M3 - Article
C2 - 22020122
AN - SCOPUS:83555166219
SN - 1748-3387
VL - 6
SP - 815
EP - 823
JO - Nature Nanotechnology
JF - Nature Nanotechnology
IS - 12
ER -
