Tetraiodothyroacetic acid-conjugated PLGA nanoparticles: a nanomedicine approach to treat drug-resistant breast cancer.

Abstract

AIM:

The aim was to evaluate tetraiodothyroacetic acid (tetrac), a thyroid hormone analog of L-thyroxin, conjugated to poly(lactic-co-glycolic acid) nanoparticles (T-PLGA-NPs) both in vitro and in vivo for the treatment of drug-resistant breast cancer.

MATERIALS & METHODS:

The uptake of tetrac and T-PLGA-NPs in doxorubicin-resistant MCF7 (MCF7-Dx) cells was evaluated using confocal microscopy. Cell proliferation assays and a chick chorioallantoic membrane model of FGF2-induced angiogenesis were used to evaluate the anticancer effects of T-PLGA-NPs. In vivo efficacy was examined in a MCF7-Dx orthotopic tumor BALBc nude mouse model.

RESULTS:

T-PLGA-NPs were restricted from entering into the cell nucleus, and T-PLGA-NPs inhibited angiogenesis by 100% compared with 60% by free tetrac. T-PLGA-NPs enhanced inhibition of tumor-cell proliferation at a low-dose equivalent of free tetrac. In vivo treatment with either tetrac or T-PLGA-NPs resulted in a three- to five-fold inhibition of tumor weight.

CONCLUSION:

T-PLGA-NPs have high potential as anticancer agents, with possible applications in the treatment of drug-resistant cancer.

• Authors: Dhruba J Bharali, Murat Yalcin, Paul J Davis, Shaker A Mousa
• Journal: Nanomedicine (London, England) (Nanomedicine (Lond)) Vol. 8 Issue 12 Pg. 1943-54 (Dec 2013) ISSN: 1748-6963 [Electronic] England
• PMID: 23448245 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Doxorubicin
• tetraiodothyroacetic acid
• Thyroxine

Topics

• Animals
• Antineoplastic Agents (chemistry, therapeutic use)
• Breast (drug effects, pathology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm
• Female
• Humans
• Lactic Acid (chemistry)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (chemistry)
• Neovascularization, Pathologic (drug therapy, pathology)
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Thyroxine (analogs & derivatives, chemistry, therapeutic use)