Nanoparticle Double Whammy Kills Tumors

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.