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Biological Chemistry

Nanoparticle Double Whammy Kills Tumors

Inactive Salmonella cells loaded with siRNA and anticancer agents show promise as delivery vehicles for a combination drug therapy

by Aaron A. Rowe
July 6, 2009 | A version of this story appeared in Volume 87, Issue 27

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Credit: EnGeneIC
In an artist's concept drawing, minicells (yellow spheres) permeate a tumor by slipping through flaws in its vasculature (red tubes at top). They then penetrate cells (large green orb, bottom) by endocytosis before releasing siRNA to knock out drug resistance. A second round of minicells (lower left) deliver an anticancer drug to finish the job of killing a tumor cell.
Credit: EnGeneIC
In an artist's concept drawing, minicells (yellow spheres) permeate a tumor by slipping through flaws in its vasculature (red tubes at top). They then penetrate cells (large green orb, bottom) by endocytosis before releasing siRNA to knock out drug resistance. A second round of minicells (lower left) deliver an anticancer drug to finish the job of killing a tumor cell.

Nanoparticles loaded with small interfering RNAs (siRNAs) can render aggressive, drug-resistant tumors more susceptible to treatment by anticancer agents, prolonging the lives of cancer-stricken mice indefinitely, according to a research team led by Jennifer A. MacDiarmid and Himanshu Brahmbhatt of EnGeneIC, an Australian biotech company (Nat. Biotechnol., DOI: 10.1038/nbt.1547). Key to the strategy is packaging siRNAs in minicells, which are 400-nm, inactive, empty bacterial cells that can function as targeted delivery vessels. The researchers used Salmonella minicells laden with some 12,000 siRNA molecules and coated with an antibody that targets tumors to squelch multidrug resistance in murine tumor xenografts. The initial si­RNA assault leaves the malignancies vulnerable to a second wave of minicells carrying irinotecan, 5-fluorouracil, or doxorubicin anticancer drugs. By pairing siRNAs and chemotherapy agents, the researchers successfully treated mice with drug doses 3,000 times lower than that required when administering a drug alone, thereby helping to prevent toxic side effects.

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