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

Horacio Cabral, Mami Murakami, Hironori Hojo, Yasuko Terada, Mitsunobu R. Kano, Ung Il Chung, Nobuhiro Nishiyama, Kazunori Kataoka

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)11397-11402
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number28
DOIs
Publication statusPublished - Jul 9 2013

Keywords

  • (1,2-Diaminocyclohexane)platinum(II)
  • Chemotherapy
  • Drug delivery

ASJC Scopus subject areas

  • General

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