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. 2009 Feb;300(2):44-51.
doi: 10.1038/scientificamerican0209-44.

Nanomedicine targets cancer

James R Heath  1 , Mark E Davis, Leroy Hood
Affiliations

Nanomedicine targets cancer

James R Heath et al. Sci Am. 2009 Feb.
No abstract available

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Figures

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NANOPARTICLES CONSTRUCTED to carry a therapeutic payload are studded with proteins that act as keys for gaining entry to tumor cells.
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PROSTATE CELLS contain groups of proteins (solid circles) that interact (lines) with one another in small networks; changes in cellular levels of certain proteins accompany a shift from health to disease. Early-stage prostate cancer cells show a rise in levels of MAPK8, a protein known to regulate cell movement. In late-stage cancer cells, levels of SDC1 are 16 times higher than in early-stage cells. Relative amounts of these two proteins can offer diagnostic clues to the presence and progression of disease.
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ON TARGET
An experimental nanotherapy, IT-101, encapsulates a chemotherapy drug, camptothecin, inside a nanoparticle designed to circulate for an extended period in the bloodstream and to accumulate in tumors. In a human safety trial, evidence of the treatment’s efficacy was seen in some patients with advanced cancers. In the CT scans below, views of a patient’s midsection show a large lung tumor (top, circled) before treatment with IT-101 and after six months of treatment (bottom), when the tumor had shrunk considerably.
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Customized Structure
The particle is built with biocompatible materials: a cyclodextrin-containing polymer (CDP) with polyethylene glycol (PEG) stalks to which transferrin proteins (Tf) are attached. Inside, as many as 2,000 siRNA molecules—the therapeutic agents—are stored.
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Passive Tumor Targeting
When the particles enter a patient’s bloodstream, they circulate freely but cannot penetrate most blood vessel walls. Tumor vessels are abnormally leaky, with large pores that allow nanoparticles to pass through and accumulate in the tumor tissue.
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Active Tumor Targeting
Transferrin receptors on the surface of a cancer cell bind to the transferrin protein on the nanoparticle, causing the cell to internalize the nanoparticle by endocytosis.
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Controlled release
Once inside the cell, a chemical sensor within the nanoparticle responds to the low pH within the endocytic vesicle by simultaneously triggering disassembly of the nanoparticle and release of the siRNA molecules that will block a gene’s instructions from being translated into a protein the cancer cell needs to survive.
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