Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis

Nanoscaled drug-loaded carriers are of particular interest for efficient tumor therapy as numerous studies have shown improved targeting and efficacy. Nevertheless, most of these studies have been performed against allograft and xenograft tumor models, which have altered microenvironment features af...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-07, Vol.110 (28), p.11397-11402
Main Authors: Cabral, Horacio, Murakami, Mami, Hojo, Hironori, Terada, Yasuko, Kano, Mitsunobu R., Chung, Ung-il, Nishiyama, Nobuhiro, Kataoka, Kazunori
Format: Article
Language:English
Subjects:
allografting
angiogenesis
Animals
Antigens
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - therapeutic use
Antineoplastics
ascites
Biological Sciences
Bioluminescence
blood serum
Cancer
carcinoma
Drug Carriers
elastase
genetic engineering
Imaging
immunity
inflammation
luciferase
Macaca mulatta polyomavirus 1
Metastasis
Mice
Micelles
nanocarriers
Pancreas
Pancreatic cancer
Pancreatic neoplasms
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - metabolism
Peritoneal Neoplasms - prevention & control
Peritoneal Neoplasms - secondary
prognosis
Rodents
Survival Analysis
Transgenic animals
Tumors
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Summary:Nanoscaled drug-loaded carriers are of particular interest for efficient tumor therapy as numerous studies have shown improved targeting and efficacy. Nevertheless, most of these studies have been performed against allograft and xenograft tumor models, which have altered microenvironment features affecting the accumulation and penetration of nanocarriers. Conversely, the evaluation of nanocarriers on genetically engineered mice, which can gradually develop clinically relevant tumors, permits the validation of their design under normal processes of immunity, angiogenesis, and inflammation. Therefore, considering the poor prognosis of pancreatic cancer, we used the elastase 1-promoted luciferase and Simian virus 40 T and t antigens transgenic mice, which develop spontaneous bioluminescent pancreatic carcinoma, and showed that long circulating micellar nanocarriers, incorporating the parent complex of oxaliplatin, inhibited the tumor growth as a result of their efficient accumulation and penetration in the tumors. The reduction of the photon flux from the endogenous tumor by the micelles correlated with the decrease of serum carbohydrate-associated antigen 19-9 marker. Micelles also reduced the incidence of metastasis and ascites, extending the survival of the transgenic mice.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1301348110