Editors' ChoiceNanotechnology

Helping the Heart to Heal

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Science Translational Medicine  26 Oct 2011:
Vol. 3, Issue 106, pp. 106ec174
DOI: 10.1126/scitranslmed.3003339

After an unexpected breakup in a relationship, one’s heart may seem inconsolable. A good friend can provide sympathy, empathy, and a reminder that “life goes on.” For the encouragement to be well-received, however, intent, timing, and delivery are crucial.

Following a myocardial infarction (a heart attack), drugs need to be administered to help dying cells in the left ventricle recover. Effective delivery of these therapeutic agents, however, has proven to be challenging. Two features of the infarcted heart encourage the application of nanotechnology to provide targeted therapy: The blood vessels in the left ventricle become leaky, and the expression of angiotensin II type 1 (AT1) receptor is increased. Dvir et al. have taken advantage of these features to design nanosized liposomes that can accumulate in the left ventricle of the heart, in a manner similar to the passive localization of nanoparticles around leaky tumor vasculature, which is often referred to as the “enhanced permeability and retention” effect. The angiotensin II amino acid sequence was also covalently attached to the nanoliposomes, allowing for preferential binding to damaged heart cells.

One day after inducing myocardial infarction in mice, Dvir and colleagues injected fluorescently labeled, AT1-targeted liposomes intravenously. Out of all tissues studied, 48% of the targeted liposomes were found in the mouse heart. Conversely, injection of nontargeted liposomes containing a scrambled amino acid sequence resulted in approximately 40% less fluorescence in isolated heart tissue than was seen for the AT1-targeted liposomes. Furthermore, in healthy control mice, cardiac accumulation of the nanoparticles was negligible. This targeted delivery strategy can reduce the toxicity of systemically delivered drugs for two reasons: First, lower doses of targeted liposomes are necessary to achieve the same therapeutic effect, and second, lesser quantities of drug will reach nontarget sites. In addition, intravenous administration can reduce the need for invasive cardiac catheterization or surgery. Such an approach may promote healing and also extend one’s opportunity to live life to the fullest…even after serious heartbreak.

T. Dvir et al., Nanoparticles targeting the infarcted heart. Nano Lett. 11, 4411–4414 (2011). [PubMed]

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