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Doxorubicin-conjugated polypeptide nanoparticles inhibit metastasis in two murine models of carcinoma.


ABSTRACT: Drug delivery vehicles are often assessed for their ability to control primary tumor growth, but the outcome of cancer treatment depends on controlling or inhibiting metastasis. Therefore, we studied the efficacy of our genetically encoded polypeptide nanoparticle for doxorubicin delivery (CP-Dox) in the syngeneic metastatic murine models 4T1 and Lewis lung carcinoma. We found that our nanoparticle formulation increased the half-life, maximum tolerated dose, and tumor accumulation of doxorubicin. When drug treatment was combined with primary tumor resection, greater than 60% of the mice were cured in both the 4T1 and Lewis lung carcinoma models compared to 20% treated with free drug. Mechanistic studies suggest that metastasis inhibition and survival increase were achieved by preventing the dissemination of viable tumor cells from the primary tumor.

SUBMITTER: Mastria EM 

PROVIDER: S-EPMC4430390 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Doxorubicin-conjugated polypeptide nanoparticles inhibit metastasis in two murine models of carcinoma.

Mastria Eric M EM   Chen Mingnan M   McDaniel Jonathan R JR   Li Xinghai X   Hyun Jinho J   Dewhirst Mark W MW   Chilkoti Ashutosh A  

Journal of controlled release : official journal of the Controlled Release Society 20150128


Drug delivery vehicles are often assessed for their ability to control primary tumor growth, but the outcome of cancer treatment depends on controlling or inhibiting metastasis. Therefore, we studied the efficacy of our genetically encoded polypeptide nanoparticle for doxorubicin delivery (CP-Dox) in the syngeneic metastatic murine models 4T1 and Lewis lung carcinoma. We found that our nanoparticle formulation increased the half-life, maximum tolerated dose, and tumor accumulation of doxorubicin  ...[more]

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