Localized doxorubicin chemotherapy with a biopolymeric nanocarrier improves survival and reduces toxicity in xenografts of human breast cancer.
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.
Cai
Shuang
S
Department of Pharmaceutical Chemistry, University of Kansas, United States.
Thati
Sharadvi
S
Bagby
Taryn R
TR
Diab
Hassam-Mustafa
HM
Davies
Neal M
NM
Cohen
Mark S
MS
Forrest
M Laird
ML
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004317:Doxorubicin; D006820:Hyaluronic Acid
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