One way to reduce the side effects of cancer chemotherapy on healthy tissues is to design targeted drugs; another is to use special delivery systems to deliver a drug specifically to the cancer cells. Tamara Minko and colleagues now report a system that delivers camptothecin selectively and effectively to ovarian cancer cells in a mouse model.

The authors constructed a targeted drug delivery system comprising polyethylene glycol (PEG) as a carrier, the anticancer agent camptothecin (CPT), and a modified luteinizing hormone-releasing hormone (LHRH) peptide as a targeting moiety. LHRH is overexpressed in ovarian cancer cells and LHRH receptors are only expressed at low levels in healthy ovarian tissue.

When mice bearing human ovarian cancer xenografts were treated with CPT alone, tumours were reduced in size, non-targeted CPT–PEG had increased activity and CPT–PEG–LHRH resulted in the greatest reduction of tumour size. Tumour-cell killing was shown to be by apoptosis, probably due to the increased concentration of CPT entering the cancer cells. To confirm the targeting of the LHRH-conjugate to the ovarian tumours, the authors looked at the distribution of tritium-labelled polymers in the treated mice. Both PEG alone and LHRH–PEG accumulated preferentially in tumour tissue — this is in line with a form of passive targeting known to occur in tumours called the enhanced permeability and retention effect. The level of accumulation of LHRH–PEG was nearly twice that of PEG alone, confirming the active tumour-targeting capacity of this polymer.

As LHRH is secreted in the pituitary gland and stimulates the production of hormones that are essential for the regulation of normal reproductive function it is vital that the drug conjugates do not cross the blood–brain barrier or affect reproductive function. In mice with or without tumours, the conjugates did not cross the blood–brain barrier and no cell death was seen in brain tissues. Furthermore, the secretion of LH by the pituitary cells was not reduced in treated mice, and all female mice were able to produce healthy viable offspring whether or not they were treated with CPT–PEG–LHRH.

So, this drug delivery system is effective at targeting ovarian cancer in mice, with reduced side-effects. As LHRH is also overexpressed in breast and prostate cancer, this system should be explored for the treatment of these cancers too.