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. 2010 Sep 1;146(2):212-8.
doi: 10.1016/j.jconrel.2010.04.006. Epub 2010 Apr 18.

Localized doxorubicin chemotherapy with a biopolymeric nanocarrier improves survival and reduces toxicity in xenografts of human breast cancer

Shuang Cai  1 , Sharadvi Thati, Taryn R Bagby, Hassam-Mustafa Diab, Neal M Davies, Mark S Cohen, M Laird Forrest
Affiliations

Localized doxorubicin chemotherapy with a biopolymeric nanocarrier improves survival and reduces toxicity in xenografts of human breast cancer

Shuang Cai et al. J Control Release. .

Abstract

Patients with metastatic breast cancer have a five-year survival rate of 27% compared to 98% for localized cancer, and the presence of even a few cancer cells in lymph nodes, known as isolated tumor cells or nanometastases, significantly increases the risk of relapse in the absence of aggressive treatment. Therefore, diagnosis and treatment of lymphatic metastases in early breast cancer plays an important role in patient survival. Here, we demonstrate the first description of a delivery system for localized doxorubicin chemotherapy to the breast tissue. The hyaluronan-doxorubicin nanoconjugate exhibits a sustained release characteristic in vitro and in vivo in the breast tissues of rodents bearing human breast cancer xenografts. In addition, the conjugate reduces dose-limiting cardiac toxicity with minimal toxicity observed in normal tissues. Finally, the conjugate dramatically inhibits breast cancer progression in vivo, leading to an increased survival rate. Thus, localized chemotherapy to the breast lymphatics with a nanocarrier may represent an improved strategy for treatment of early stage breast cancers.

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Figures

Figure 1
Figure 1
Synthesis of hyaluronan-doxorubicin (HA-DOX) conjugate (left panel). In vitro release of DOX from HA-DOX at pH 5.0, 6.0 and 7.4 (right panel).
Figure 2
Figure 2
Serum DOX concentration-time curves.
Figure 3
Figure 3
Heart tissues of HA-DOX (left panel), DOX (middle panel) and underlying tissues of the HA-DOX injection site (right panel).
Figure 4
Figure 4
Imaging of HA-DOX in the primary tumor and the surrounding lymphatics (day 1–9). HA-DOX was injected peritumorally (white arrows) with most of the carrier draining to the adjacent nodes (blue arrow). After spectrum unmixing and false coloring, the total DOX (within red circle) and tumoral DOX (within black circle) were integrated and normalized to day 0. Doxorubicin is false colored white-yellow-red with decreasing intensity.
Figure 5
Figure 5
See this image and copyright information in PMC

References

    1. Takemura G, Fujiwara H. Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management. Prog Cardiovasc Dis. 2007;49(5):330–352. - PubMed
    1. Matsumura Y, Hamaguchi T, Ura T, Muro K, Yamada Y, Shimada Y, Shirao K, Okusaka T, Ueno H, Ikeda M, Watanabe N. Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin. Br J Cancer. 2004;91(10):1775–1781. - PMC - PubMed
    1. Rihova B, Strohalm J, Prausova J, Kubackova K, Jelinkova M, Rozprimova L, Sirova M, Plocova D, Etrych T, Subr V, Mrkvan T, Kovar M, Ulbrich K. Cytostatic and immunomobilizing activities of polymer-bound drugs: experimental and first clinical data. J Control Release. 2003;91(1–2):1–16. - PubMed
    1. Tolcher AW, Sugarman S, Gelmon KA, Cohen R, Saleh M, Isaacs C, Young L, Healey D, Onetto N, Slichenmyer W. Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer. J Clin Oncol. 1999;17(2):478–484. - PubMed
    1. National Cancer Institute. Breast cancer PDQ treatment. 2007. [Access date 10/29/2009]. < http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional>.

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