Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size.
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 inhibitor to increase the permeability of the tumours.
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Japan.
H
H
Cabral
Y
Y
Matsumoto
K
K
Mizuno
Q
Q
Chen
M
M
Murakami
M
M
Kimura
Y
Y
Terada
M R
MR
Kano
K
K
Miyazono
M
M
Uesaka
N
N
Nishiyama
K
K
Kataoka
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D004337:Drug Carriers / Q000493:pharmacokinetics*; D006801:Humans; D008081:Liposomes / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D011720:Pyrazoles / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D011804:Quinolines
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D008823:Micelles; D009944:Organoplatinum Compounds; D011092:Polyethylene Glycols; D011720:Pyrazoles; D011758:Pyrroles; D016212:Transforming Growth Factor beta; C506615:HTS 466284; D011804:Quinolines; C013933:dichloro-1,2-diaminocyclohexane platinum complex